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Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders
Open accessAbstract
Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need for improved drug treatments. In this review an overview of drugs being studied in different phases of clinical trials for their potential in the treatment of fear-, anxiety- and trauma-related disorders is presented. One strategy followed in drug development is refining and improving compounds interacting with existing anxiolytic drug targets, such as serotonergic and prototypical GABAergic benzodiazepines. A more innovative approach involves the search for compounds with novel mechanisms of anxiolytic action using the growing knowledge base concerning the relevant neurocircuitries and neurobiological mechanisms underlying pathological fear and anxiety. The target systems evaluated in clinical trials include glutamate, endocannabinoid and neuropeptide systems, as well as ion channels and targets derived from phytochemicals. Examples of promising novel candidates currently in clinical development for generalised anxiety disorder, social anxiety disorder, panic disorder, obsessive compulsive disorder or post-traumatic stress disorder include ketamine, riluzole, xenon with one common pharmacological action of modulation of glutamatergic neurotransmission, as well as the neurosteroid aloradine. Finally, compounds such as D-cycloserine, MDMA, L-DOPA and cannabinoids have shown efficacy in enhancing fear-extinction learning in humans. They are thus investigated in clinical trials as an augmentative strategy for speeding up and enhancing the long-term effectiveness of exposure-based psychotherapy, which could render chronic anxiolytic drug treatment dispensable for many patients. These efforts are indicative of a rekindled interest and renewed optimism in the anxiety drug discovery field, after decades of relative stagnation.
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TL;DR
This review surveys novel pharmacological targets in clinical development for anxiety and anxiety-related disorders, covering refinements of existing serotonergic and GABAergic targets as well as compounds acting on glutamate, endocannabinoid, neuropeptide, ion channel, and phytochemical targets. It also reviews drugs used to augment exposure-based psychotherapy via fear-extinction enhancement, concluding that renewed interest and optimism have returned to a field stagnant since the approvals of pregabalin and duloxetine.
Key findings
- Current first-line pharmacotherapy (SSRIs, SNRIs) yields meta-analytic response rates of 40–75% (mean 55%), with delayed onset (2–3 weeks or more) and substantial non-response, relapse, and tolerability problems; no new drug has been approved for any anxiety or related disorder since pregabalin (2006) and duloxetine (2007).
- As of the review, 12 compounds have entered Phase 3, 25 are in Phase 2, and 8 are in Phase 1 for anxiety and trauma-related disorders, with most drugs evaluated for PTSD.
- Promising novel candidates modulating glutamatergic neurotransmission include ketamine, riluzole/troriluzole, and xenon; a single intravenous ketamine dose reduced core PTSD symptom severity at 24 h to the same extent as the active comparator midazolam, and xenon inhalation in an open-label study of 80 PD patients reduced panic attacks and general anxiety for up to 6 months.
- Extinction-enhancing adjuncts to exposure-based therapy include D-cycloserine (most studied, but meta-analyses show only small if any clinical effects), MDMA (six Phase 2 trials showed clinically relevant PTSD symptom reductions lasting ~3.5 years), L-DOPA, and cannabinoids; the neurosteroid aloradine (PH94B) reduced performance and social interaction anxiety within 15 min of intranasal application in SAD patients.
Methods
- Narrative review; the authors conducted a comprehensive search of clinicaltrials.gov for ongoing trials (active, not yet recruiting, recruiting, enrolling by invitation, recently suspended as of September 2018, updated April 2019) involving pharmacotherapy for GAD, SAD, specific phobias, PD, PTSD, and OCD, complemented by open internet searches for press releases and announcements, with identified compounds then used as PubMed search terms.
- The review synthesizes preclinical and clinical studies and approved/ongoing trials across four development avenues: refining existing targets, novel mechanisms of action, phytochemicals, and pharmacological augmentation of psychotherapy.
- No primary data collection or meta-analysis was performed; findings are presented in narrative form with summary tables (Tables 2 and 3) of compounds, mechanisms, sponsors, phases, and trial identifiers.
Limitations
- The paper states that the neurobiology underlying anxiety and the exact mechanisms of therapeutic treatments remain incompletely understood, and that the study of epigenetic drug targets for anxiety remains in its infancy with unclear superiority over existing treatments.
- The authors note that most phytochemical evidence comes from animal models, with few clinical trials and limited sample sizes, and that structure-activity relationships, metabolism, absorption, and mechanisms are unclear for most phytochemicals.
- The text makes evident (not framed as author-stated limitations) that many cited trials are ongoing with data not yet available, that several key findings rest on open-label, pilot, or small studies (e.g., the 80-patient xenon study, the 21-patient BHV-0223 SAD study), and that the review's clinicaltrials.gov search was current only to April 2019.
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226 Not checked yet · 28 No basis given · 20 Own interpretation · 1 Supported so far · 1 Partly supported · 1 Couldn’t confirm · accuracy not yet measured
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In the paper
“During the period of its suspension, it was revealed that these problems were due to off-target effects of this agent that led to alterations in lipid networks in the cortexeffects which were not observed in more specific FAAH inhibitors (van Esbroeck et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.2. FAAH inhibitors
What the sources say
- Partly supportedcites van Esbroeck et al., 2017 sourceExperimental — accuracy not yet measured
The Main text reports off-target activity and broad lipid changes in human cortical neuron cultures treated with BIA 10-2474, compared with more restricted changes after PF04457845. But its conclusion explicitly says the data do not establish that off-target inhibition caused the clinical neurotoxicity; the citing sentence presents that proposed explanation as fact. Page numbers are not provided in our copy. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Two small studies involving OXT augmentation for EBT in patients with SAD (Guastella, Howard, Dadds, Mitchell, & Carson, 2009) and arachnophobia (Acheson, Feifel, Kamenski, McKinney, & Risbrough, 2015) had disappointing preliminary outcomes.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.1. Facilitating fear-extinction mechanisms
What the sources say
- Not checked yetcites Guastella, Howard, Dadds, Mitchell, & Carson, 2009 source
- Supportedcites Acheson, Feifel, Kamenski, McKinney, & Risbrough, 2015 source
The Introduction describes a preliminary trial of intranasal oxytocin before exposure therapy for arachnophobia, and the Discussion calls the sample fairly small. The Discussion reports that oxytocin impeded self-reported treatment response and never produced superior outcomes to placebo. This citation supports the arachnophobia study; the separate SAD study has its own citation. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
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The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“For example, it has been reported that negative emotional pictures were perceived as less aversive after a single dose of MDMA in healthy humans (Kuypers, Dolder, Ramaekers, & Liechti, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Could not verifycites Kuypers, Dolder, Ramaekers, & Liechti, 2017 sourceExperimental — accuracy not yet measured
The Methods section (page unavailable) says participants viewed negative emotional pictures, but rated arousal and concern, not aversiveness. The Results section (page unavailable) reports empathy and emotion-recognition outcomes; searches for ‘less aversive’ and ‘aversive’ found no passage stating that MDMA made the pictures seem less aversive. (LLM, conf=0.74)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, most drugs are evaluated for the indication PTSD”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Approximately 20 pharmaceutical companies as well as several academic consortia (Table 2) are involved in these trials at present”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, BDZs demonstrate efficacy for the treatment of GAD (Gomez, Barthel, & Hofmann, 2018) and are still and even increasingly prescribed (Agarwal & Landon, 2019;Bachhuber, Hennessy, Cunningham, & Starrels, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 2. Overview and historical account of current medication options for anxiety and related disorders
What the sources say
- Not checked yetcites Gomez, Barthel, & Hofmann, 2018 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Selective serotonin (5-HT) reuptake inhibitors (SSRIs), including for example (es)citalopram, sertraline, fluoxetine are currently first-line drug treatment options for most anxiety disorders as they are proposed to have a better benefit/risk ratio than any other form of current pharmacotherapy (Bandelow, Michaelis, & Wedekind, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 2. Overview and historical account of current medication options for anxiety and related disorders
What the sources say
- Not checked yetcites Bandelow, Michaelis, & Wedekind, 2017 source
hedged- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need for improved drug treatments.”
- Also stated in: § 2. Overview and historical account of current medication options for anxiety and related disorders · hedged
“Such problems suggest that current therapies are insufficient and they have rekindled the interest to develop drugs with novel mechanisms of action to improve this situation, particularly for non-responding patients.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > Abstract
plain- Asserted: passes — The authors put it forward as true.
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- Also stated in: § 2. Overview and historical account of current medication options for anxiety and related disorders · hedged
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In the paper
“since the approval of pregabalin (13 years ago) and of duloxetine (12 years) ago (Fig. 1), no new drug has passed the EMA and/or FDA authorities to allow its use for the treatment of any anxiety or related disorder.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 3. Problems with, and failures in, anxiolytic drug development
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- Rests on an assumption: Duloxetine and pregabalin were approved by FDA and/or EMA for GAD in 2006/07.
None of the sources cited for this claim have been checked yet.
In the paper
“In contrast, BDZs demonstrate efficacy for the treatment of GAD (Gomez, Barthel, & Hofmann, 2018) and are still and even increasingly prescribed (Agarwal & Landon, 2019;Bachhuber, Hennessy, Cunningham, & Starrels, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 2. Overview and historical account of current medication options for anxiety and related disorders
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In general, b10% of promising CNS drug candidates identified in preclinics and taken to humans make it through the clinical development to the market and the clinical development and approval of CNS drugs takes longer than any other drug class (Kaitin, 2014(Kaitin, , 2018)).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 3. Problems with, and failures in, anxiolytic drug development
What the sources say
- Not checked yetcites Kaitin, 2014
- Not checked yetcites Kaitin, 2018
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Selective serotonin (5-HT) reuptake inhibitors (SSRIs), including for example (es)citalopram, sertraline, fluoxetine are currently first-line drug treatment options for most anxiety disorders as they are proposed to have a better benefit/risk ratio than any other form of current pharmacotherapy (Bandelow, Michaelis, & Wedekind, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 2. Overview and historical account of current medication options for anxiety and related disorders
What the sources say
- Not checked yetcites Bandelow, Michaelis, & Wedekind, 2017 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“This low overall success rate of compounds in clinical development is costly and has led to a 50% decline in CNS drug discovery and development programs by major pharmaceutical companies from 2009 to 2014, while university led drug discovery centres targeting neurological and psychiatric indications have increased considerably in numbers in the last years (Nutt & Attridge, 2014;Yokley, Hartman, &”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 3. Problems with, and failures in, anxiolytic drug development
What the sources say
- Not checked yetcites Nutt & Attridge, 2014
- Not checked yetcites Yokley, Hartman, & Slusher, 2017
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Meta-analyses across different drug treatments found response rates between 40 and 75%, with a mean of 55% (Greener, 2009;Loerinc et al., 2015;Mitte, Noack, Steil, & Hautzinger, 2005).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 2. Overview and historical account of current medication options for anxiety and related disorders
What the sources say
- Not checked yetcites Greener, 2009
- Not checked yetcites Loerinc et al., 2015 source
- Not checked yetcites Mitte, Noack, Steil, & Hautzinger, 2005
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Medical interventions, including SSRIs [e.g.(Doruyter et al., 2016;Schmidt et al., 2018)], and other pharmacological treatments (Fig. 3), as well as (exposure-based) CBT [e.g.(Brooks & Stein, 2015;King et al., 2016;Neufang et al., 2019;Steiger et al., 2017); see scheme in Excursus 2 in (Sartori & Singewald, 2017)] have been shown to affect and in part normalise important aspects of such dysf”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.1. Circuitry
What the sources say
- Not checked yetcites Doruyter et al., 2016 source
- Not checked yetcites Schmidt et al., 2018
- Not checked yetcites Brooks & Stein, 2015
plainconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In particular, pathologically heightened fear/anxiety seems to be commonly associated with increased amygdala activation in response to negative emotional stimuli (Etkin & Wager, 2007).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.1. Circuitry
What the sources say
- Not checked yetcites Etkin & Wager, 2007 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Treatments including pharmacotherapy work by restoring balance in affected neurochemistry and circuitries (Carlisi & Robinson, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.1. Circuitry
What the sources say
- Not checked yetcites Carlisi & Robinson, 2018
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Increasing evidence suggests that these circuitry treatment effects are mediated by changes in synaptic plasticity in key areas of the circuitry (Krystal et al., 2017;Luchkina & Bolshakov, 2018;Mahan & Ressler, 2012;Mansson et al., 2016;Mansson et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.1. Circuitry
What the sources say
- Not checked yetcites Krystal et al., 2017 source
- Not checked yetcites Luchkina & Bolshakov, 2018
- Not checked yetcites Mahan & Ressler, 2012
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“However, there is evidence that changes in neuroplasticity (e.g.changes in neurite growth, dendritic spine density, synapse number, intrinsic excitability, etc) important to reshape circuitries and connectivity can be produced even within 24 hours by compounds including ketamine, psychedelics and N-methyl-D-aspartate (NMDA) receptor partial agonists [Fig.3; (Olson, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.1. Circuitry
What the sources say
- Not checked yetcites Olson, 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Further maladaptations in other brain areas, including the thalamus and the striatum, have been observed in an anxiety disorder-specific manner (Brooks & Stein, 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.1. Circuitry
What the sources say
- Not checked yetcites Brooks & Stein, 2015
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Specifically, the amygdala, which receives inputs e.g. from the thalamus, the medial prefrontal cortex (mPFC), and the hippocampus, modulates corresponding behavioural and physiological responses via projections that extend from its central nucleus to multiple regions, including the hypothalamus, the bed nucleus of the stria terminalis, the brainstem and the periaqueductal grey, that finally elic”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.1. Circuitry
What the sources say
- Not checked yetcites Calhoon & Tye, 2015 source
- Not checked yetcites Farb & Ratner, 2014
- Not checked yetcites Goodkind & Etkin, 2018
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, there are important constraints in this translation such as the uniqueness of human endophenotypes, cognitive traits, processes and brain structures that have been highlighted in various reviews [see e.g.: (Andrews, Papakosta, & Barnes, 2014;Cryan & Sweeney, 2011;Flores et al., 2018;Freudenberg, O'Leary, Aguiar, & Slattery, 2018;Haller, Aliczki, & Gyimesine Pelczer, 2013;Harro, 2018;Ste”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4. Neurobiology of fear and anxiety as a potential source of innovation and progress
What the sources say
- Not checked yetcites Andrews, Papakosta, & Barnes, 2014
- Not checked yetcites Cryan & Sweeney, 2011
- Not checked yetcites Flores et al., 2018 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“With these precautions in mind, basic anxietyrelated processes are increasingly being identified and successfully replicated in other species including humans (Stewart et al. 2014;Mohammad et al. 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4. Neurobiology of fear and anxiety as a potential source of innovation and progress
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, alterations in the structure, function and connectivity of the amygdala, the mPFC, the anterior cingulate cortex and the insula as well as more recently the bed nucleus of the stria terminalis [due to advances in the imaging techniques (Robinson, Pike, Cornwell, & Grillon, 2019)] are suggested to contribute to the development and maintenance of anxiety disorders in humans (Duval et al”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.1. Circuitry
What the sources say
- Not checked yetcites Duval et al., 2015
- Not checked yetcites Etkin & Wager, 2007 source
- Not checked yetcites Fox & Kalin, 2014
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“an increased connectivity between the rostral ACC and the amygdala after adminstration of a benzodiazepine (Leicht et al., 2013)”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
- Not checked yetcites Leicht et al., 2013 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Finally, compounds such as D-cycloserine, MDMA, L-DOPA and cannabinoids have shown efficacy in enhancing fear-extinction learning in humans.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Examples of promising novel candidates currently in clinical development for generalised anxiety disorder, social anxiety disorder, panic disorder, obsessive compulsive disorder or post-traumatic stress disorder include ketamine, riluzole, xenon with one common pharmacological action of modulation of glutamatergic neurotransmission, as well as the neurosteroid aloradine.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“This control of the ventromedial PFC [in humans; the homologous region in rodents is the infralimbic cortex (IL)] over the amygdala is important in modulating negative bias in anxiety (Carlisi & Robinson, 2018) or in fear extinction, a key fear-inhibitory mechanism underlying exposure-based therapy (EBT) [Section 8; (Heilbronner, Rodriguez-Romaguera, Quirk, Groenewegen, & Haber, 2016;Sartori &”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.1. Circuitry
What the sources say
- Not checked yetcites Carlisi & Robinson, 2018
- Not checked yetcites Heilbronner, Rodriguez-Romaguera, Quirk, Groenewegen, & Haber, 2016
- Not checked yetcites Sartori & Singewald, 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“increased global brain connectivity in the dmPFC and dlPFC following a single ketamine infusion (Abdallah et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
- Not checked yetcites Abdallah et al., 2018
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The target systems evaluated in clinical trials include glutamate, endocannabinoid and neuropeptide systems, as well as ion channels and targets derived from phytochemicals.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“They are thus investigated in clinical trials as an augmentative strategy for speeding up and enhancing the long-term effectiveness of exposure-based psychotherapy, which could render chronic anxiolytic drug treatment dispensable for many patients.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“clinical genetics have been able to identify various susceptibility genes, including the 5-HT transporter 5-HTT, 5-HT 1A receptor, monoamine oxidase A, catechol-O-methyltransferase, phosphodiesterase 4B and the brain-derived neurotrophic factor (BDNF) gene, involved in specific anxiety-relevant phenotypes and/or in in the aetiology and maintenance of pathological anxiety in a non-specific or disor”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They are thus investigated in clinical trials as an augmentative strategy for speeding up and enhancing the long-term effectiveness of exposure-based psychotherapy, which could render chronic anxiolytic drug treatment dispensable for many patients.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Evidence indicates that different types of recent life stressors and negative life events may cause similar anxiety symptoms in humans by different neurobiological pathways [see e.g., (Gonda et al., 2019;Hassell Jr., Nguyen, Gates, & Lowry, 2018)].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
- Not checked yetcites Gonda et al., 2019 source
- Not checked yetcites Hassell Jr., Nguyen, Gates, & Lowry, 2018
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“altered DNA methylation patterns in GAD (Gottschalk & Domschke, 2017), PD (Iurato et al., 2017) or adolescents with anxiety disorder (Bortoluzzi et al., 2018) have been found.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“suggesting a considerable role for environmental factors (such as stress) and the epigenome (Hettema, Prescott, Myers, Neale, & Kendler, 2005).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
- Not checked yetcites Hettema, Prescott, Myers, Neale, & Kendler, 2005
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“sum up to moderate heritability (e.g.30% in GAD) of anxiety disorders”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
- Not checked yetcites Hettema, Prescott, Myers, Neale, & Kendler, 2005
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“gene-gene interactions, as for example between variants of the CB 1 receptor (CNR1) promoter and the functional polymorphism of the 5-HT transporter, may differentially affect anxiety and the vulnerability to side effects of drugs in humans [for review see (Lazary, Juhasz, Hunyady, & Bagdy, 2011)].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
- Not checked yetcites Lazary, Juhasz, Hunyady, & Bagdy, 2011
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The role of epigenetics as modulatory factors between the genetic predisposition and environmental experiences (Kuehner, Bruggeman, Wen, & Yao, 2019) has been increasingly recognized in anxiety (Alisch et al., 2017;Wang, Lou, & Wang, 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
- Not checked yetcites Kuehner, Bruggeman, Wen, & Yao, 2019
- Not checked yetcites Alisch et al., 2017 source
- Not checked yetcites Wang, Lou, & Wang, 2019
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the contributions of each of these and additional genetic variants to disease risk are small (1-2%)”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
- Not checked yetcites Hettema, Prescott, Myers, Neale, & Kendler, 2005
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Information derived from altered genetic and epigenetic profiles in anxiety may be useful markers of disease and/or treatment response.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“These include monoaminergic, GABA-ergic, glutamatergic, neuropeptidergic and eCB systems and there is evidence for dysregulation in each of these systems in a variety of brain regions of different anxiety-related disorders [e.g.(Bandelow et al., 2016;Maron et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.3. Neurochemistry
What the sources say
- Not checked yetcites Bandelow et al., 2016
- Not checked yetcites Maron et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The growing knowledge concerning neurobiological mechanisms of anxiety and anxiolytic drug action supports drug development for anxiety-related disorder.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.3. Neurochemistry
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Evidence in support of an involvement of inflammation in anxiety disorders has been gained so far mainly by investigating peripheral levels of cytokines, e.g. in GAD (Costello, Gould, Abrol, & Howard, 2019), PD (Petrowski, Wichmann, & Kirschbaum, 2018), PTSD (Passos et al., 2015) and OCD (Rao et al., 2015) patients.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.3. Neurochemistry
What the sources say
- Not checked yetcites Costello, Gould, Abrol, & Howard, 2019
- Not checked yetcites Petrowski, Wichmann, & Kirschbaum, 2018
- Not checked yetcites Passos et al., 2015 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“neuroinflammation has recently been recognized as a potential pathophysiological mechanism contributing to the onset and/or maintenance at least in subgroups of anxiety patients, opening the possibility to propose immune-targeting interventions as complementary or alternative routes of treatment (Furtado & Katzman, 2015;Gaspersz et al., 2017;Kim & Jeon, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.3. Neurochemistry
What the sources say
- Not checked yetcites Furtado & Katzman, 2015
- Not checked yetcites Gaspersz et al., 2017 source
- Not checked yetcites Kim & Jeon, 2018
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Immune targeting interventions to produce anxiolytic effects are just beginning to evolve with some interesting indicative preliminary findings involving classical (Makunts, Cohen, Lee, & Abagyan, 2018) and non-classical multitarget anti-inflammatory agents with anxiolytic properties such as N-acteylcysteine (Santos, Herrmann, Elisabetsky, & Piato, 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.3. Neurochemistry
What the sources say
- Not checked yetcites Makunts, Cohen, Lee, & Abagyan, 2018
- Not checked yetcites Santos, Herrmann, Elisabetsky, & Piato, 2019
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The contributions of 5-HT 1A , 5-HT 1B , 5-HT 2C , 5-HT 4 , 5-HT 6 and 5-HT 7 receptors are still not entirely clear, as anxiolytic effects are observed after both their stimulation and their blockade in a brain-area-dependent manner [see (Zmudzka, Salaciak, Sapa, & Pytka, 2018) for a recent review].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1. Monoamine systems
What the sources say
- Not checked yetcites Zmudzka, Salaciak, Sapa, & Pytka, 2018
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Moreover, different serotonergic pathways affect anxiety-like, anti-depressant and antiimpulsive behaviour (Ohmura et al., 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1. Monoamine systems
What the sources say
- Not checked yetcites Ohmura et al., 2019
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“5-HT signalling is known to modulate the communication between key constituents of fear and anxiety circuitries (Babaev, Piletti Chatain, & Krueger-Burg, 2018;Carhart-Harris & Nutt, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1. Monoamine systems
What the sources say
- Not checked yetcites Babaev, Piletti Chatain, & Krueger-Burg, 2018
- Not checked yetcites Carhart-Harris & Nutt, 2017 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, how these strategies finally translate into the clinics, is not entirely clear due to the complex regulation of the 5-HT system upon pharmacological intervention causing adaptations in receptor expression and 5-HT release.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1. Monoamine systems
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“one proposed network action of SSRIs involves diminishing anxiety-relevant negative bias in a 'bottom-up' manner, by altering amygdala and anterior cingulate cortex reactivity to negative cues targeting subcortical regions of the so-called survival circuitries that are implicated in anticipation, reactivity, regulation and learning of affective cues [Fig.3; (Young & Craske, 2018)].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1. Monoamine systems
What the sources say
- Not checked yetcites Young & Craske, 2018
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“a contribution of specific 5-HT receptors to the various adverse effects of SSRIs has been proposed, such as for example sexual dysfunction [5-HT 1A ; (Olivier, 2015)] or a paradoxical anxiogenic response to subchronic SSRI treatment (Turcotte-Cardin et al., 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1. Monoamine systems
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“recent meta-analyses asserted that vilazodone was superior to placebo in the short-term treatment of GAD, with small effect sizes (Slee et al., 2019;Stuivenga et al., 2019;Zareifopoulos & Dylja, 2017)”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.1. Vilazodone
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In contrast, symptoms of PTSD and comorbid depression have not been found to be improved by vilazodone (Ramaswamy et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.1. Vilazodone
What the sources say
- Not checked yetcites Ramaswamy et al., 2017 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This observation is in contrast to evidence derived from patients with depression, where good tolerability of vilazodone was reported (Shi et al., 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.1. Vilazodone
What the sources say
- Not checked yetcites Shi et al., 2016 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“patients were more likely to discontinue drug than placebo treatment due to the occurrence of adverse events, including nausea and diarrhea (Slee et al., 2019;Zareifopoulos & Dylja, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.1. Vilazodone
What the sources say
- Not checked yetcites Slee et al., 2019 source
- Not checked yetcites Zareifopoulos & Dylja, 2017
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“preclinical evidence of anxiolytic and antidepressant properties has stimulated further investigation for its use in GAD and major depression as well as for schizophrenia and multiple sclerosis (Ivachtchenko, Lavrovsky, & Okun, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.2. AVN-101
What the sources say
- Not checked yetcites Ivachtchenko, Lavrovsky, & Okun, 2016
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Preclinical findings in animal models of anxiety predict anxiolytic efficacy in humans.
In the paper
“although brexpiprazole exerts only low affinity to the D 1 receptor, it has been shown to facilitate glutamatergic transmission via D 1 receptor dependent mechanisms in the mPFC that could also be important for its anxiety-modulating effects (Bjorkholm, Marcus, Konradsson-Geuken, Jardemark, & Svensson, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.3. Brexpiprazole
What the sources say
- Not checked yetcites Bjorkholm, Marcus, Konradsson-Geuken, Jardemark, & Svensson, 2017
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“early improvements in anxiety scores with the drug might predict a positive response and facilitated remission in GAD [ (Clayton et al., 2017)].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.1. Vilazodone
What the sources say
- Not checked yetcites Clayton et al., 2017
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“While a Phase 3 study evaluating the efficacy of brexpiprazole as adjunctive treatment to paroxetine or sertraline for PTSD symptoms (NCT01987960) was terminated due to problems with patient eligibility”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.3. Brexpiprazole
What the sources say
- Not checked yetcites NCT01987960
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In comparison with a placebo, it also improved sustained remission rates at 12 weeks of treatment when given at bedtime to treat military-related PTSD.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.4. Cyclobenzaprine VLD (TNX-102)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Tonmya® reduced the symptoms of PTSD in two randomised, placebo-controlled Phase 2 studies (NCT02277704, NCT02421679).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.4. Cyclobenzaprine VLD (TNX-102)
What the sources say
- Not checked yetcites NCT02277704
- Not checked yetcites NCT02421679
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In a retrospective subgroup analysis gepirone ER was found to reduce clinical scores of somatic and psychic anxiety in patients with depression and anxious depression (Alpert, Franznick, Hollander, & Fava, 2004).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.5. Gepirone ER (Travivo®)
What the sources say
- Not checked yetcites Alpert, Franznick, Hollander, & Fava, 2004
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Cyclobenzaprine is an antagonist at 5-HT 2A , α 1 and H 1 receptors (Daugherty, Sullivan, Gershell, & Lederman, 2015)”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.4. Cyclobenzaprine VLD (TNX-102)
What the sources say
- Not checked yetcites Daugherty, Sullivan, Gershell, & Lederman, 2015
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Animal and human studies have established the critical role of both the GABA-A and the GABA-B receptors in the processing of anxiety, as well as in the pathogenesis and pathology of anxiety disorders (Bandelow et al., 2016;Engin et al., 2018;Nuss, 2015;Pizzo, O'Leary, & Cryan, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2. GABA system
What the sources say
- Not checked yetcites Bandelow et al., 2016
- Not checked yetcites Engin et al., 2018 source
- Not checked yetcites Nuss, 2015
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Its anxiolytic effect seems to be a result of the synergistic action of this action, antagonising 5-HT 2C receptors in subcortical areas including hippocampus and the MT receptor stimulation enhancing neurogenesis and reducing stress-induced glutamate release (Levitan et al., 2015;Tardito, Molteni, Popoli, & Racagni, 2012).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.6. Compounds with potential anxiolytic properties on hold/discontinued for drug development in anxiety Vortioxetine
What the sources say
- Not checked yetcites Levitan et al., 2015 source
- Not checked yetcites Tardito, Molteni, Popoli, & Racagni, 2012
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These are important findings which suggest that any remaining agonistic efficacy at the α 1 subtype is undesirable in the development of non-sedative BDZ anxiolytics.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.1. Benzodiazepines
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Currently there are no subtype-selective GABA-A receptor ligands in clinical trials for anxiety disorders (Table 2).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.1. Benzodiazepines
What the sources say
- Not checked yetcites Table 2
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is thus proposed that α 2 and α 3 subtype partial agonists with α 1 dormancy may cause little sedation and amnesia in parallel with no or low abuse potential or tolerance building.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.1. Benzodiazepines
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“It has been shown that the potency of BDZ may play a role in tolerance development, as full agonists produce more tolerance than partial agonists (Cheng et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.1. Benzodiazepines
What the sources say
- Not checked yetcites Cheng et al., 2018 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“several compounds, including L-838,417, imidazenil, TPA123, TPA023, ocinaplon and MRK-409, have demonstrated anxiolytic effects in rodents and/or primates, with reduced or no sedative effects.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.1. Benzodiazepines
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Preclinical findings in animal models of anxiety predict anxiolytic efficacy in humans.
In the paper
“Stress that is considered a risk factor in the development of anxiety disorders alters levels of glutamate in rodents, and, indeed, patients with an anxiety disorder display abnormal levels of glutamate and glutamate receptors (Krystal et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Krystal et al., 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“and, indeed, patients with an anxiety disorder display abnormal levels of glutamate and glutamate receptors (Krystal et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Krystal et al., 2017 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Liebowitz and co-workers reported the results of a randomised clinical trial demonstrating that 15 min after its intranasal application, aloradine already reduced performance anxiety and social interaction anxiety to a greater extent than a placebo in a provoked public-speaking challenge in female patients diagnosed with generalised SAD (Liebowitz et al., 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Liebowitz et al., 2014 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The principal concept that synthetic and/or natural neurosteroids may be considered as anxiety treatment is supported by the increasing evidence of altered neurosteroid homeostasis in anxiety and related disorders (Aspesi & Pinna, 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Aspesi & Pinna, 2019
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Aloradine does not bind to monoaminergic, glutamatergic, peptidergic, opioid, glucocorticoid or sex-hormone receptors (Liebowitz et al., 2016) and it is not clear whether it targets the GABA-A receptor.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Liebowitz et al., 2016 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Despite these efforts, we still know relatively little about the glutamate system in the pathogenesis and perpetuation of anxiety disorders (Bandelow et al., 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Bandelow et al., 2016
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Although its use is limited by reports of the occurrence of adverse effects such cutaneous reactions, hepatotoxicity, colitis and metrorrhagia in a substantial number of people (Cottin et al., 2016), the therapeutic profile of this drug is interesting for drug development.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Cottin et al., 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This transmission pathway is neuronally connected to basal forebrain areas rapidly affecting neuronal activity in the amygdala, the hypothalamus and the PFC, as well as autonomic and behavioural responses (Liebowitz et al., 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Liebowitz et al., 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“It is reported that in an everyday life setting aloradine rapidly improves symptoms of social anxiety in participants who were allowed to self-administer aloradine nasal spray 15 min prior to an upcoming feared situation (Liebowitz et al., 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Liebowitz et al., 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“First, in the mPFC and hippocampus blockade of GluN1/GluN2C containing NMDA receptors located preferentially on GABAergic interneurons by ketamine causes disinhibition and (persistently) enhances AMPA receptor-mediated excitatory neurotransmission.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This fact, however, seems to be critical as anaesthetic doses of ketamine do not produce antidepressant effects (Zorumski, Izumi, & Mennerick, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
- Not checked yetcites Zorumski, Izumi, & Mennerick, 2016 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While some promising examples are given below, testing results of the mGluR5 negative allosteric modulator RHG-618 or of the selective mGluR2 PAM JNJ-40411813 (=ADX-71149) for the indication depression with anxiety and/or anxiety disorders in Phase 1 and 2 clinical trials were not sufficiently convincing to suggest further development.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“At subanaesthetic doses ketamine reaches brain concentrations that allow modulation of specific subpopulations of NMDA receptors (Dravid et al., 2007, Kotermanski, Wood, & Johnson, 2009).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
- Not checked yetcites Dravid et al., 2007 source
- Not checked yetcites Kotermanski, Wood, & Johnson, 2009
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“There is strong preclinical evidence that drugs reducing glutamatergic neurotransmission cause fast antidepressant and anxiolytic effects in animals and humans (Williams & Sanacora, 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Williams & Sanacora, 2015
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In a double-blind, randomised clinical trial a single dose of intravenous ketamine has been shown to reduce core symptom severity in patients with chronic PTSD 24 h post treatment to the same extent as the active BDZ comparator midazolam (Feder et al., 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
- Not checked yetcites Feder et al., 2014 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“a single ketamine infusion (0.5 mg/kg) caused fast and prolonged (for at least a week) clinically relevant relief of OCD symptoms (Rodriguez et al., 2013), while a negative outcome was reported in an open trial (Bloch et al., 2012).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
- Not checked yetcites Rodriguez et al., 2013 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“while a negative outcome was reported in an open trial (Bloch et al., 2012).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
- Not checked yetcites Bloch et al., 2012 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“This idea is supported by preclinical findings showing that xenon reduces NMDAinduced synaptic currents and neuronal plasticity in brain areas involved in fear learning and memory processes including the amygdala and hippocampus (Haseneder et al., 2008;Kratzer et al., 2012).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.2. Xenon gas (NBTX-001)
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In animals, inhalation of sub-anaesthetic concentrations of xenon (25% for 1 h) was shown to reduce fear-related behaviour by impairing fear memory reconsolidation suggesting that xenon inhalation may have potential for therapeutic blocking of trauma memory reconsolidation (Meloni, Gillis, Manoukian, & Kaufman, 2014)”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.2. Xenon gas (NBTX-001)
What the sources say
- Not checked yetcites Meloni, Gillis, Manoukian, & Kaufman, 2014
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“CBD furthermore increases eCB levels, in particular of AEA (Crippa, Guimaraes, Campos, & Zuardi, 2018;Soares & Campos, 2017) and has been shown to modulate the activity in anxiety-relevant brain areas including the mPFC, hippocampus and amygdala”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.1. Cannabis
What the sources say
- Not checked yetcites Crippa, Guimaraes, Campos, & Zuardi, 2018 source
- Not checked yetcites Soares & Campos, 2017
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“and has been shown to modulate the activity in anxiety-relevant brain areas including the mPFC, hippocampus and amygdala [see Fig. 3; (Crippa et al., 2018)].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.1. Cannabis
What the sources say
- Not checked yetcites Crippa et al., 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Cannabis use or cannabis use disorder is positively associated with anxiety in the general population, likely used as selfmedication (Kedzior & Laeber, 2014), and is particularly common in patients with PTSD (Gentes et al., 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.1. Cannabis
What the sources say
- Not checked yetcites Kedzior & Laeber, 2014
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“and in mice lacking the 2-AG synthesising enzyme diacylglycerol lipase anxiety-related behaviour is enhanced (Jenniches et al., 2016;Shonesy et al., 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.3. Other targets in the eCB system
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The development of the FAAH inhibitor SSR-411298 by Sanofi for the treatment of major depression and anxiety was discontinued after the disappointing outcome of a Phase 2b trial in elderly patients (Mandrioli & Mercolini, 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.2. FAAH inhibitors
What the sources say
- Not checked yetcites Mandrioli & Mercolini, 2015
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“AEA levels have been shown to be reduced in PTSD patients (Hill et al., 2013;Neumeister et al., 2013) and depressed patients with high anxiety scores (Hill, Miller, Carrier, Gorzalka, & Hillard, 2009;Hill, Miller, Ho, Gorzalka, & Hillard, 2008).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.2. FAAH inhibitors
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In patients with PTSD or depression 2-AG plasma levels have been found to be lower than in healthy controls (Hauer et al., 2013), and in mice lacking the 2-AG synthesising enzyme diacylglycerol lipase anxiety-related behaviour is enhanced (Jenniches et al., 2016;Shonesy et al., 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.3. Other targets in the eCB system
What the sources say
- Not checked yetcites Hauer et al., 2013 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“and depressed patients with high anxiety scores (Hill, Miller, Carrier, Gorzalka, & Hillard, 2009;Hill, Miller, Ho, Gorzalka, & Hillard, 2008).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.2. FAAH inhibitors
What the sources say
- Not checked yetcites Hill, Miller, Carrier, Gorzalka, & Hillard, 2009
- Not checked yetcites Hill, Miller, Ho, Gorzalka, & Hillard, 2008 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In rodent studies, both the pharmacological and the genetic inhibition of FAAH cause anxiolytic-like effects, in particular under highly aversive or stressful conditions (Patel et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.2. FAAH inhibitors
What the sources say
- Not checked yetcites Patel et al., 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“When COX-2 is inhibited, AEA and, to a lesser extent, 2-AG accumulate in the brain (Hermanson et al., 2013).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.3. Other targets in the eCB system
What the sources say
- Not checked yetcites Hermanson et al., 2013 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Diverse neuropeptides are expressed and released in regions of anxiety/fear neurocircuitries, often together with classical transmitters (Hökfelt et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3. Neuropeptide systems
What the sources say
- Not checked yetcites Hökfelt et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Substrate selective COX-2 inhibitors have demonstrated robust anxiolytic effects in rodents (Gamble-George et al., 2016;Patel et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.3. Other targets in the eCB system
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Increasing central 2-AG concentrations by inhibiting MAG-L, its main degrading enzyme, reduces anxiety-related behaviours in rodents (Patel et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.3. Other targets in the eCB system
What the sources say
- Not checked yetcites Patel et al., 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, V 1A and V 1B receptor antagonists have demonstrated anxiolytic and antidepressant effects in preclinical studies (Bleickardt et al., 2009;Hodgson et al., 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.1. Vasopressin system: SRX246
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Studies in humans showed that the release of vasopressin was significantly correlated with anxiety symptoms in healthy volunteers after anxiogenic drug challenge (Abelson, Le Melledo, & Bichet, 2001).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.1. Vasopressin system: SRX246
What the sources say
- Not checked yetcites Abelson, Le Melledo, & Bichet, 2001
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“While the development of V 1B receptor antagonists (e.g.SSR149415) was discontinued for the treatment of anxiety disorders because it did not meet the efficacy expectations (Griebel & Holsboer, 2012), the brain-penetrating smallmolecule”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.1. Vasopressin system: SRX246
What the sources say
- Not checked yetcites Griebel & Holsboer, 2012
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In animals, OXT has demonstrated anxiolytic, (social) fear-reducing and extinctionfacilitating effects (see Section 8) in various established paradigms (Jurek & Neumann, 2018;Naja & Aoun, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.2. Oxytocin system
What the sources say
- Not checked yetcites Jurek & Neumann, 2018 source
- Not checked yetcites Naja & Aoun, 2017
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In a Phase 1 clinical trial, SRX246 demonstrated a good safety profile upon single and repeated ascending dosing (Fabio et al., 2013) and attenuated amygdala activation in response to angry faces (Fig. 3) and vasopressin administration indicating a role of amygdalar V 1A receptors in the processing of aversive emotional information (Lee et al., 2013).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.1. Vasopressin system: SRX246
What the sources say
- Not checked yetcites Fabio et al., 2013 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the brain-penetrating smallmolecule selective V 1A receptor antagonist SRX246 (Azevan Pharmaceuticals) decreased aggression, anxiety, depression, fear and stress in male and female adults with intermittent explosive disorder in a multi-centre randomised Phase 2 exploratory study (Azevan, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.1. Vasopressin system: SRX246
What the sources say
- Not checked yetcites Azevan, 2016
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, SRX246 is considered promising for further clinical development as a treatment for PTSD and GAD as well as anger disorders.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.1. Vasopressin system: SRX246
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“OXT is proposed to counteract stressassociated responses, including fear (Naja & Aoun, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.2. Oxytocin system
What the sources say
- Not checked yetcites Naja & Aoun, 2017
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The nonapeptide OXT, traditionally known for its role in milk letdown and uterine contraction during labour and often termed the 'love hormone', is also released during stressful situations in brain areas associated with anxiety, fear and stress responses, including the mPFC, the hypothalamus, the hippocampus and the amygdala (Neumann & Slattery, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.2. Oxytocin system
What the sources say
- Not checked yetcites Neumann & Slattery, 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Furthermore, OXT was shown to affect functional coupling of mPFC and amygdala in healthy participants (Dodhia et al., 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.2. Oxytocin system
What the sources say
- Not checked yetcites Dodhia et al., 2014 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“OXT applied via this route has been shown to exert rapid anxiolysis also in humansfor example, in patients with GAD [for review, see (Neumann & Slattery, 2016)].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.2. Oxytocin system
What the sources say
- Not checked yetcites Neumann & Slattery, 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In rodents these compounds have mostly been shown to be anxiolytic (Kaffman, White, Wei, Johnson, & Krystal, 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Kaffman, White, Wei, Johnson, & Krystal, 2019
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The orexin receptor 1 and/or orexin receptor 2 receptor are expressed in several brain areas that are engaged during anxiety and fear processing including the hippocampus, amygdala and mPFC (Flores, Saravia, Maldonado, & Berrendero, 2015;Marcus et al., 2001).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.3. Orexin system
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In patients with PTSD low levels of NPY in the cerebrospinal fluid are correlated with the presence of intrusive traumatic memory and heightened amygdala response (Reichmann & Holzer, 2016;Wu et al., 2011).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Reichmann & Holzer, 2016
- Not checked yetcites Wu et al., 2011
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These findings have raised interest in the therapeutic potential of substances that antagonise orexin signalling for the treatment of anxiety disorders, in particular for PD, PTSD and phobias (James, Campbell, & Dayas, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.3. Orexin system
What the sources say
- Not checked yetcites James, Campbell, & Dayas, 2017
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In highly socially anxious individuals intranasal OXT reduces attentional bias for emotional faces to the level of healthy individuals suggesting the potential therapeutic use of this form of OXT in the treatment of social anxiety (Clark-Elford et al., 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.2. Oxytocin system
What the sources say
- Not checked yetcites Clark-Elford et al., 2014
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Along the same lines, OXT preferentially enhances prosocial behaviours in SAD patients (Fang, Treadway, & Hofmann, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.2. Oxytocin system
What the sources say
- Not checked yetcites Fang, Treadway, & Hofmann, 2017
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In a recent randomised clinical Phase 1 trial in patients with PTSD, intranasally administrated NPY showed a greater reduction in anxiety symptoms in a dose-dependent manner along with good tolerability than placebo, supporting the push for further studies investigating the efficacy and safety of the repeated administration of NPY”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Sayed et al., 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“At the moment it is not clear whether and how the existing rodent data concerning the pronounced anxiolytic effects of NPS can be translated into humans in particular due to lacking information on the exact distribution of NPS and its receptors system in the human brain and the lack of orally bioavailable and blood-brain barrier penetrating NPS receptor agonists (Sartori & Singewald, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Sartori & Singewald, 2017 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“it may be that only subpopulations of patients are sensitive to their therapeutic effects that need to be further investigated (Spierling & Zorrilla, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Spierling & Zorrilla, 2017 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This resulted in the discontinuation of the substance P programmes of major pharmaceutical companies (Ebner, Sartori, & Singewald, 2009).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Ebner, Sartori, & Singewald, 2009
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In Phase 2 clinical trials, however, the efficacy of several neurokinin 1, neurokinin 2 and neurokinin 3 receptor antagonists, including vestipitant, orvepitant, saredudant and osanetant, in reducing symptoms in patients with GAD, SAD, PTSD and PD was inconsistent or negative.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Ebner, Sartori, & Singewald, 2009
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: In animal studies, substance P modulates anxiety-related behaviour via its three neurokinin receptors.
In the paper
“Nevertheless, the recent finding that there is a positive correlation between neurokinin 1 receptor expression in the amygdala and trait anxiety, could stimulate further research on neurokinin 1 receptor antagonists as potential anxiolytics, at least for specific subpopulations of patients (Hoppe et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Hoppe et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Thus, it is proposed that an overstimulation of NPS-sensitive circuits in A/T SNP carriers may contribute to the development of anxiety-and stress-related disorders [for recent review, see (Grund & Neumann, 2019)].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Grund & Neumann, 2019
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“So far, in terms of the assessed clinical evidence of anxiolytic efficacy of phytochemicals, one plant stands out: kava.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7. Phytochemicals
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In August 2018, Biohaven reported that BHV-0223 met the primary endpoint of significantly reducing anxiety in the 21 recruited patients with SAD (www.Biohavenpharma.com).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.4. Voltage-gated ion channels 6.4.1. Riluzole and Troriluzole
What the sources say
- Not checked yetcites www.Biohavenpharma.com
plaindirectn = 21- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Riluzole was shown to reduce clinical symptoms in adults with treatment-refractory OCD when used as add-on to existing pharmacotherapy, including SSRIs and antipsychotics (Coric et al., 2005;Pittenger et al., 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.4. Voltage-gated ion channels 6.4.1. Riluzole and Troriluzole
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“However, modulation of the GABA system has been revealed as one important mechanism of several phytochemicals (Savage et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7. Phytochemicals
What the sources say
- Not checked yetcites Savage et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Anxiolytic effects are reported following administration of natural compounds and formulations derived from Piper methysticum (kava), Centella asiatica (pennywort), Humulus lupulus (hops), Ginkgo biloba (maiden hair), Matricaria chamomilla (chamomile), Melissa officinalis (lemon balm), Passiflora incarnata (maypop), Scuterllaria leriflora (skullcap), Valeriana officinalis (valerian), Withania somn”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7. Phytochemicals
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Despite this limited evidence, a proportion of anxiety patients are known to favour alternative therapies, including phytotherapy (McIntyre, Saliba, Wiener, & Sarris, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7. Phytochemicals
What the sources say
- Not checked yetcites McIntyre, Saliba, Wiener, & Sarris, 2016
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Subsequent trials in patients with GAD also reported a greater decrease in anxiety scores with kava than with a placebo that already exerted a strong effect (Connor, Payne, & Davidson, 2006).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7.1. Kava
What the sources say
- Not checked yetcites Connor, Payne, & Davidson, 2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A Cochrane meta-analysis of the anxiolytic efficacy of kava, including seven placebo-controlled trials, revealed a small, though significant, overall effect size on the reduction in the anxiety rating in patients with neurotic, non-psychotic, generalised or pre-operative anxiety receiving kava extract (Pittler & Ernst, 2003).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7.1. Kava
What the sources say
- Not checked yetcites Pittler & Ernst, 2003
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“CBT, focusing on exposure to feared cues to promote extinction learning (Craske, Treanor, Conway, Zbozinek, & Vervliet, 2014), continues to be the most widely used and most strongly validated psychotherapeutic treatment for both youth and adult anxiety disorders (Barry, Yeung, & Lau, 2018;Kodal et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8. Pharmacological augmentation of psychotherapy
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Four weeks of treatment with hops (Humulus lupulus) caused a greater reduction in self-reported anxiety, depression and stress symptoms in healthy young adults in comparison with a placebo (Kyrou et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7.2. Other plants in clinical development
What the sources say
- Not checked yetcites Kyrou et al., 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The most recent meta-analysis attributes only small, if at all, clinical effects of DCS augmentation of EBT for the treatment of anxiety disorders, OCD or PTSD (Burkner, Bittner, Holling, & Buhlmann, 2017;Mataix-Cols et al., 2017;Stojek, McSweeney, & Rauch, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.1. Facilitating fear-extinction mechanisms
What the sources say
- Not checked yetcites Burkner, Bittner, Holling, & Buhlmann, 2017
- Not checked yetcites Mataix-Cols et al., 2017 source
- Not checked yetcites Stojek, McSweeney, & Rauch, 2018
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Research elucidating the protein-synthesis-dependent processes underlying the formation and maintenance of fear and extinction memories has revealed that maladaptive associative fear memories can be destabilised and edited (for a recent review see Phelps & Hofmann, 2019) upon their retrieval, when memories enter a transient, labile state preceding reconsolidation processes.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.2. Targeting fear-memory-(re)consolidation mechanisms
What the sources say
- Not checked yetcites Phelps & Hofmann, 2019
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In healthy participants, intranasal OXT has been shown to facilitate the extinction of conditioned fear (Acheson et al., 2013;Eckstein et al., 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.1. Facilitating fear-extinction mechanisms
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In patients with refractory PTSD, a preliminary meta-analysis has recently revealed greater efficacy of MDMA-assisted psychotherapy compared to prolonged exposure therapy (Amoroso & Workman, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.1. Facilitating fear-extinction mechanisms
What the sources say
- Not checked yetcites Amoroso & Workman, 2016
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, the benefit of DCS-augmented EBT seems to be reduced in patients receiving antidepressants (King et al., 2018;Otto et al., 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.1. Facilitating fear-extinction mechanisms
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Finally, there is also some initial evidence that psilocybin may be beneficial in OCD (Moreno, Wiegand, Taitano, & Delgado, 2006), and this is now being further explored in two Phase 2 trials using lorazepam and niacin as comparators (NCT03356483, NCT03300947, Table 2).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Moreno, Wiegand, Taitano, & Delgado, 2006
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“MDMA, apart from its fear-extinction-facilitating effects (see above), exerts entactogenic effects, i.e. it enhances feelings of love, happiness and closeness to others (Simmler & Liechti, 2018)”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Simmler & Liechti, 2018
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“For example, the classic serotonergic psychedelics LSD and psilocybin (magic mushrooms) have been shown to alter the state of consciousness in a way that is thought to be helpful during psychotherapeutic interventions (Liechti, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Liechti, 2017 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Importantly, 5-HT 2A receptor signalling has also been implicated in processes of neuroplasticity, such as neurogenesis, neurodevelopment, learning, including extinction learning, cognitive flexibility and enhanced environmental sensitivity (Liechti, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Liechti, 2017 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“One of the problems of psychotherapy is the non-adherence of the patients that is driven by various factors including low motivation for treatment, poor readiness for change and poor therapeutic alliance (Taylor et al., 2012).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Taylor et al., 2012 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A significant and sustained decrease of anxiety scores in patients with life-threatening diseases has been reported in an open-label randomised study following LSD-assisted psychotherapy (Gasser, Kirchner, & Passie, 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Gasser, Kirchner, & Passie, 2015 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“However, these studies have yielded mixed results (Walsh, Das, Saladin, & Kamboj, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.2. Targeting fear-memory-(re)consolidation mechanisms
What the sources say
- Not checked yetcites Walsh, Das, Saladin, & Kamboj, 2018 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The noted trend towards the off-label prescription of medicinal cannabis/marijuana or nabilone for patients with anxiety disorders may reflect the fact that there has been a considerable lag in developing really new and effective evidence-based treatments in this field, and in psychiatry in general (Kolar, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
What the sources say
- Not checked yetcites Kolar, 2018 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the studies involving ketamine suggest that greater efficacy and more rapid onset than with current first line pharmacotherapy (e.g.SSRIs) are possible in different anxiety disorders, and even in treatment-resistant patient populations.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“has been shown to elicit rapid anxiolysis in animals and in humans (Feduccia et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Feduccia et al., 2018
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the glutamate system as a target may hold particular promise for mediating rapid and large anxiolytic effects, even in patients who are resistant to established therapy.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“For instance, MDMA has demonstrated anxiolytic effects when administered to patients suffering from a life-threatening illness (Liechti, 2017)”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Liechti, 2017 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“it has been found to reduce social anxiety in adults with autism spectrum disorder (Danforth et al., 2018;Danforth, Struble, Yazar-Klosinski, & Grob, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Danforth et al., 2018 source
- Not checked yetcites Danforth, Struble, Yazar-Klosinski, & Grob, 2016
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“randomised clinical trials, although limited in number, have revealed promising evidence of rapidly reducing anxiety symptoms through CB 1 receptor activation by natural or synthetic cannabinoids or the use of FAAH inhibitors including JNJ-42165279.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“the expectation that highly selective agents acting on specific molecular targets would yield better and safer psychiatric drugs has not been realised (Griebel & Holmes, 2013;Millan, Goodwin, Meyer-Lindenberg, & Ove Ogren, 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
What the sources say
- Not checked yetcites Griebel & Holmes, 2013
- Not checked yetcites Millan, Goodwin, Meyer-Lindenberg, & Ove Ogren, 2015 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on available data concerning novel drugs, examples of possible sustained symptom relief include mainly the combination of drugs with cognitive behavioural therapy (CBT) so far.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.3. Drug discovery process refinements
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Over the last few decades, anxiolytic drug discovery focused on the utilisation of single targets.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“none of the putative blood-based, genetic, epigenetic, neurochemical, metabolic or neuroimagery biomarkers are sufficiently specific, valid and reliable as diagnostic tools or markers of treatment response in anxiety disorders (Bandelow et al., 2016;Lueken et al., 2016;Maron et al., 2018)”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.1. Biomarkers and personalized treatment
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“some of the drug candidates in development, such as aloradine, xenon-gas, MDMA, agomelatine, psychedelics and kava constituents, represent multimodal drugs.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“overcoming of the blood-brain barrier which profoundly limits the oral administration of antibodies, peptides and polar molecules (Danon, Reekie, & Kassiou, 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.3. Drug discovery process refinements
What the sources say
- Not checked yetcites Danon, Reekie, & Kassiou, 2019
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 103
- The quote only partly states this claim. 1
- Probably not a substantial claim. 21
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Currently, 12 compounds have entered Phase 3 of clinical development, 25 compounds are in Phase 2 and eight compounds are in Phase 1 for the treatment of different forms of anxiety and trauma-related disorders, as summarised in Table 3.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“there has recently been a kind of revival of the potential medicinal use of psychedelics, including LSD and psilocybin, as potential adjuncts to psychotherapy in anxiety treatment.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
In the paper
“Taken together, there is still an urgent need for the development of novel approaches in the treatment of anxiety and related disorders (Griebel & Holmes, 2013).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 1. Introduction
What the sources say
- Not checked yetcites Griebel & Holmes, 2013
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
- Rests on an assumption: The onset of therapeutic action of antidepressants is delayed for 2-3 weeks or more.
None of the sources cited for this claim have been checked yet.
In the paper
“This low overall success rate of compounds in clinical development is costly and has led to a 50% decline in CNS drug discovery and development programs by major pharmaceutical companies from 2009 to 2014, while university led drug discovery centres targeting neurological and psychiatric indications have increased considerably in numbers in the last years (Nutt & Attridge, 2014;Yokley, Hartman, &”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 3. Problems with, and failures in, anxiolytic drug development
What the sources say
- Not checked yetcites Nutt & Attridge, 2014
- Not checked yetcites Yokley, Hartman, & Slusher, 2017
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Between 50 and 60% of all failures of CNS drugs are the result of poor efficacy/efficiency, while poor safety accounts for 20-30% of failures (McArthur, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 3. Problems with, and failures in, anxiolytic drug development
What the sources say
- Not checked yetcites McArthur, 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Between 50 and 60% of all failures of CNS drugs are the result of poor efficacy/efficiency, while poor safety accounts for 20-30% of failures (McArthur, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 3. Problems with, and failures in, anxiolytic drug development
What the sources say
- Not checked yetcites McArthur, 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, full clinical remission is often not achieved, a significant number of patients does not respond to treatment or they relapse after treatment cessation even after an initial positive response (Batelaan et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 2. Overview and historical account of current medication options for anxiety and related disorders
What the sources say
- Not checked yetcites Batelaan et al., 2017 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In general, b10% of promising CNS drug candidates identified in preclinics and taken to humans make it through the clinical development to the market and the clinical development and approval of CNS drugs takes longer than any other drug class (Kaitin, 2014(Kaitin, , 2018)).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 3. Problems with, and failures in, anxiolytic drug development
What the sources say
- Not checked yetcites Kaitin, 2014
- Not checked yetcites Kaitin, 2018
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Enhanced amygdala responsivity is often associated with hyperactivity in a network that mediates the anticipation of negative outcomes and consists of the anterior cingulate cortex, insula, dorsolateral PFC and the medial orbitofrontal cortex, and hypoactivity in inhibitory systems, for example involving the ventromedial PFC, which is implicated in top-down inhibition of amygdala output [Fig.3;”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.1. Circuitry
What the sources say
- Not checked yetcites Schmidt, Khalid, Loukas, & Tubbs, 2018
- Not checked yetcites Tovote et al., 2015 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such problems suggest that current therapies are insufficient and they have rekindled the interest to develop drugs with novel mechanisms of action to improve this situation, particularly for non-responding patients.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 2. Overview and historical account of current medication options for anxiety and related disorders
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Hence, although fear and anxiety are distinct (Perusini & Fanselow, 2015;Parsafar & Davis, 2018), there are clear overlaps, as well as co-occurrence, as anxiety often follows a fearful experience and in turn modulates the fear responses to a threat.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 1. Introduction
What the sources say
- Not checked yetcites Perusini & Fanselow, 2015
- Not checked yetcites Parsafar & Davis, 2018
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These efforts are indicative of a rekindled interest and renewed optimism in the anxiety drug discovery field, after decades of relative stagnation.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“findings of a reduced dmPFC/dorsal ACC-amygdala or amygdala-BNST connectivity following treatment with SSRIs (Grillon, Robinson, Cornwell, & Ernst, 2019;Robinson et al., 2019)”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
- Not checked yetcites Grillon, Robinson, Cornwell, & Ernst, 2019
- Not checked yetcites Robinson et al., 2019 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A more innovative approach involves the search for compounds with novel mechanisms of anxiolytic action using the growing knowledge base concerning the relevant neurocircuitries and neurobiological mechanisms underlying pathological fear and anxiety.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“One strategy followed in drug development is refining and improving compounds interacting with existing anxiolytic drug targets, such as serotonergic and prototypical GABAergic benzodiazepines.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“histone-deacetylase inhibitors may be useful in anxiety disorders, by promoting relevant gene expression (Sah et al., 2019;Tran, Schulkin, Ligon, & Greenwood-Van Meerveld, 2015;Whittle & Singewald, 2014) and targeting also some common comorbidities of anxiety disorders (Moloney, Stilling, Dinan, & Cryan, 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Disturbances in the composition of the microbiome have been linked to anxiety (Lach et al., 2018;Leclercq et al., 2016) and treatments aimed at normalising these disturbances using specific probiotics have been proposed (Yang, Wei, Ju, & Chen, 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.3. Neurochemistry
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At present the study of epigenetic drug targets for anxiety remains in its infancy, and it is not clear yet whether these agents actually offer superior outcomes to existing treatments.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 4.2. Genetics and epigenetics
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“SSRIs in particular are recommended as first-line treatment for various different anxiety disorders (Table 1).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1. Monoamine systems
What the sources say
- Not checked yetcites Table 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“F13714 is a substance that acts as a full agonist at presynaptic 5-HT 1A receptors only and exerts anxiolytic and fearreducing effects in animals (Depoortere, Bardin, Varney, & Newman-Tancredi, 2019;Zhao et al., 2019), but has not been tested in humans so far.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1. Monoamine systems
What the sources say
- Not checked yetcites Depoortere, Bardin, Varney, & Newman-Tancredi, 2019
- Not checked yetcites Zhao et al., 2019 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Preclinical findings in animal models of anxiety predict anxiolytic efficacy in humans.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“It has been suggested that stimulation of 5-HT 2B and the blockade of 5-HT 2A , 5-HT 3 , and probably 5-HT 5A receptors are important for inducing anxiolytic effects.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1. Monoamine systems
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Buspirone, approved for the treatment of GAD (Table 1, Fig. 1) is an example of such a strategy.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1. Monoamine systems
What the sources say
- Not checked yetcites Table 1
- Not checked yetcites Fig. 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“vilazodone treatment demonstrated greater improvement in anxiety measures than placebo treatment in a randomised controlled study for adult separation anxiety (Schneier et al., 2017) and in generalised SAD (Careri, Draine, Hanover, & Liebowitz, 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.1. Vilazodone
What the sources say
- Not checked yetcites Schneier et al., 2017 source
- Not checked yetcites Careri, Draine, Hanover, & Liebowitz, 2015
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A Phase 1b trial, completed in 2018, reported that after treatment with AVN-101 for several weeks, the occurrence of adverse events was low and that it was well tolerated in a wide range of doses.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.2. AVN-101
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The atypical antipsychotic brexpiprazole is an antagonist at the 5-HT 2A , 5-HT 2B and 5-HT 7 receptors, a partial agonist at the 5-HT 1A as well as dopamine D 2 and D 3 receptors and has antagonistic properties at the α 1 -adrenoceptor, the α 2 -adrenreoceptor and the histaminergic H 1 receptor (Maeda et al., 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.3. Brexpiprazole
What the sources say
- Not checked yetcites Maeda et al., 2014 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although there is little evidence of sexual dysfunction (Shi, Wang, Xu, & Lu, 2016) and of treatment-emergent suicidal ideation (Thase et al., 2017)”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.1. Vilazodone
What the sources say
- Not checked yetcites Shi, Wang, Xu, & Lu, 2016
- Not checked yetcites Thase et al., 2017 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“a recent meta-analysis provides some support for the potential of vortioxetine for the treatment of anxiety (Yee, Ng, & Seng, 2018), whereby it seems to be more efficient in lowering relapse rate and improving quality of life in adults integrated into the working world or in education than in non-engaged subjects (Christensen, Loft, Florea, & McIntyre, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.6. Compounds with potential anxiolytic properties on hold/discontinued for drug development in anxiety Vortioxetine
What the sources say
- Not checked yetcites Yee, Ng, & Seng, 2018
- Not checked yetcites Christensen, Loft, Florea, & McIntyre, 2017
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“So far, FKW00GA has been shown to be safe and well tolerated and there is some evidence of efficacy in patients with GAD as assessed in several Phase 2 clinical trials.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.5. Gepirone ER (Travivo®)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“The antidepressant vortioxetine, developed by Lundbeck and Takeda and approved in 2013, is a 5-HT 3 , 5-HT 7 and 5-HT 1D receptor antagonist, a 5-HT 1B receptor partial agonist, a 5-HT 1A receptor agonist and an inhibitor of the 5-HT transporter (Bang-Andersen et al., 2011) with a good tolerability and long-term safety profile and no evidence of sexual dysfunction as a side effect.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.6. Compounds with potential anxiolytic properties on hold/discontinued for drug development in anxiety Vortioxetine
What the sources say
- Not checked yetcites Bang-Andersen et al., 2011 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This evidence is supported by previous studies showing that the immediate release formulation of gepirone was able to improve anxiety ratings as compared with placebo with similar efficacy to the comparator diazepam.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.5. Gepirone ER (Travivo®)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The azapirone gepirone is a full 5-HT 1A receptor agonist at raphe 5-HT 1A autoreceptors and a partial agonist at postsynaptic 5-HT 1A receptors.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.5. Gepirone ER (Travivo®)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Travivo®, by Fabre-Kramer Pharmaceuticals, is the extended-release (ER) formulation of gepirone reducing fluctuations in plasma drug concentrations and the incidence of adverse events that were associated with high peak plasma concentrations (Robinson, Sitsen, & Gibertini, 2003).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.5. Gepirone ER (Travivo®)
What the sources say
- Not checked yetcites Robinson, Sitsen, & Gibertini, 2003
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Cyclobenzaprine is proposed to improve sleep quality via its blockade of 5-HT 2A and H 1 receptors (Krystal, Richelson, & Roth, 2013;Monti, 2011), and to reduce trauma-related nightmares and sleep disturbance via blockade of α1-adrenoceptors (Hendrickson & Raskind, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.4. Cyclobenzaprine VLD (TNX-102)
What the sources say
- Not checked yetcites Krystal, Richelson, & Roth, 2013
- Not checked yetcites Monti, 2011 source
- Not checked yetcites Hendrickson & Raskind, 2016
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Another 5-HT 1A receptor partial agonist developed by Fabre-Kramer Pharmaceuticals is FKW00GA that also exerts 5-HT 2A receptor antagonistic properties.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.5. Gepirone ER (Travivo®)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“in a retrospective analysis it was revealed that Tonmya® exerted clinically significant effects only in that subgroup of PTSD patients in whom the trauma had been experienced within nine years prior to study participation, but no longer than that (Sullivan et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.4. Cyclobenzaprine VLD (TNX-102)
What the sources say
- Not checked yetcites Sullivan et al., 2018
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Since agomelatine has been shown to positively affect sleep-related measures including REM and slow wave sleep and the quality of sleep (Buoli et al., 2017;Guardiola-Lemaitre et al., 2014;Levitan et al., 2015), it is likely to be particularly useful for anxiety patient populations with sleep-related symptoms including also PTSD and OCD (De Berardis et al., 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.6. Compounds with potential anxiolytic properties on hold/discontinued for drug development in anxiety Vortioxetine
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Findings and treatments for one anxiety disorder generalize to other anxiety disorders.
None of the sources cited for this claim have been checked yet.
In the paper
“Agomelatine has a unique mechanism of action (Levitan, Papelbaum, & Nardi, 2015) as it is an agonist at the G-protein coupled melatonin MT 1 and MT 2 receptors and an antagonist at the 5-HT 2C and 5-HT 2B receptors with very low binding affinity to most other monoaminergic, GABAergic and glutamatergic receptors as well as to potassium and calcium channels (Millan et al., 2003).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.6. Compounds with potential anxiolytic properties on hold/discontinued for drug development in anxiety Vortioxetine
What the sources say
- Not checked yetcites Levitan, Papelbaum, & Nardi, 2015
- Not checked yetcites Millan et al., 2003
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“BDZs, which have been in clinical use for decades, not only exhibit rapid anxiolytic effects, but also have sedative, amnestic, anticonvulsant, muscle relaxant and addictive properties (Coric et al., 2005;Engin et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.1. Benzodiazepines
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“vortioxetine was shown to decrease the number of panic attacks and to moderately improve the quality of life of patients with PD in an open-label trial with flexible doses (Shah & Northcutt, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.6. Compounds with potential anxiolytic properties on hold/discontinued for drug development in anxiety Vortioxetine
What the sources say
- Not checked yetcites Shah & Northcutt, 2018
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“agomelatine, developed by Servier, has been approved for the treatment of major depressive disorder in Europe since 2009, and was shown to have anxiolytic properties (Stein et al., 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.6. Compounds with potential anxiolytic properties on hold/discontinued for drug development in anxiety Vortioxetine
What the sources say
- Not checked yetcites Stein et al., 2014 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that vortioxetine could be beneficial for some groups of anxiety patients, but this needs to be further evaluated in long-term placebo-controlled studies and/or in postmarket surveys of patients with depression.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.1.6. Compounds with potential anxiolytic properties on hold/discontinued for drug development in anxiety Vortioxetine
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The key neuronal circuits and brain areas mediating the anxiolytic effects of BDZs are still not entirely clear, although the limbic system, and the amygdala in particular, has been revealed as a central component (Engin et al., 2018;Griessner et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.1. Benzodiazepines
What the sources say
- Not checked yetcites Engin et al., 2018 source
- Not checked yetcites Griessner et al., 2018
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, etifoxine exerts its anxiolytic effects without sedation and ataxia via two mechanisms of action at the GABA-A receptor: a direct action as a PAM binding to the β 2 and β 3 subunits of the GABA-A receptor preferentially potentiating α2β3γ2S and α3β3γ2S containing GABA-A receptors, and indirectly by stimulating the biosynthesis of neurosteroids including 17-hydroxypregnenolone that”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Mattei et al., 2019 source
- Not checked yetcites Nuss, Ferreri, & Bourin, 2019
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although it is not approved by the FDA or EMA, it is marketed in approximately 40 countries including France (approved in 1979) for the treatment of anxiety disorders (Poisbeau et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Poisbeau et al., 2018 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“They act as positive allosteric modulators (PAMs) on compatible GABA-A receptors and thus increase GABA-induced chloride conductance and inhibitory postsynaptic potentials (Olsen & Sieghart, 2009).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.1. Benzodiazepines
What the sources say
- Not checked yetcites Olsen & Sieghart, 2009
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The preclinical research for such ligands is still ongoing (Prevot et al., 2019) in parallel with the identification of novel interesting subunit-specific target sites at the GABA-A receptor such as the α 6 subunit (Gonda et al., 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.1. Benzodiazepines
What the sources say
- Not checked yetcites Prevot et al., 2019
- Not checked yetcites Gonda et al., 2019 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Preclinical findings in animal models of anxiety predict anxiolytic efficacy in humans.
None of the sources cited for this claim have been checked yet.
In the paper
“In healthy humans, only TPA023 with α1 antagonistic properties, but not MRK-409 with weak α1 partial agonistic effects, causes sedation-free anxiolysis (de Haas et al., 2007), as well as in patients with GAD as shown in Phase 2 trials (Atack, 2009).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.1. Benzodiazepines
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Aloradine lacks affinity for the steroid hormone receptors, but binds with high affinity to the nasal chemosensory receptors in humans, a group of G-protein coupled receptors that mediate the detection of pheromone signals.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Liebowitz et al., 2016 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Glutamate is the principal excitatory neurotransmitter in the brain, and it exerts its various biological functions via the fast-acting ionotropic N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid receptor (AMPA) and kainate receptors, as well as the mGluR1-8 (Reiner & Levitz, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Reiner & Levitz, 2018
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“and indirectly by stimulating the biosynthesis of neurosteroids including 17-hydroxypregnenolone that potentiate GABA-A receptor activity (Mattei et al., 2019;Nuss, Ferreri, & Bourin, 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
What the sources say
- Not checked yetcites Mattei et al., 2019 source
- Not checked yetcites Nuss, Ferreri, & Bourin, 2019
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both BDNF and mTOR complex appear to be the key effectors for rapidly enhancing synaptic connectivity and increasing dendritic spines (Castren & Hen, 2013;Fortress, Smith, & Pang, 2018) and are proposed to underlie the persistent antidepressant effects of ketamine.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
- Not checked yetcites Castren & Hen, 2013 source
- Not checked yetcites Fortress, Smith, & Pang, 2018
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Ketamine was also shown to reduce anxiety symptoms in adults with treatment-refractory GAD (Glue et al., 2017) and with SAD, with reported increased social engagement on subsequent days (Taylor et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Forth, there is recent evidence that ketamine also causes increased stimulation of postsynaptic 5-HT1A receptors in the mPFC activating the phosphoinositide-3 kinase/Akt/mTOR complex pathway further downstream (Fukumoto, Iijima, Funakoshi, & Chaki, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
- Not checked yetcites Fukumoto, Iijima, Funakoshi, & Chaki, 2018
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“its safety has to be carefully evaluated when given at higher doses over a longer period of time as it elicits euphoric and dissociative effects and may increase the incidence of cardiovascular effects, hepatotoxicity and ulcerative cystitis (Cohen et al., 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
- Not checked yetcites Cohen et al., 2018
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similar to ketamine, the NMDA receptor antagonist AZD6765, or lanicemine (AstraZeneca), a blocking molecule that is trapped inside the NMDA channel pore, exerts rapid, but short-lived, antidepressant effects in clinical trials without evidence of eliciting psychotomimetic effects (Zarate Jr. et al., 2013).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
- Not checked yetcites Zarate Jr. et al., 2013 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although ketamine treatment was generally well tolerated in these clinical trials and S-ketamine (esketamine) has just been approved for the treatment of treatment-resistant depression by the FDA in form of a nasal spray (FDA, 2019; The Scientist, 2019), its safety has to be carefully evaluated when given at higher doses over a longer period of time as it elicits euphoric and dissociative effects”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.1. Ketamine
What the sources say
- Not checked yetcites FDA, 2019
- Not checked yetcites The Scientist, 2019
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Pharmacologically, it is a multi-target agent reducing excitatory neurotransmission by inhibition of the NMDA receptor (by competing with the co-agonist glycine at aromatic residues of the glycine binding site), AMPA-, nicotinic acetylcholine, 5-HT 3 receptors and HCN (hyperpolarization-activated cyclic nucleotide-gated) channels and causing neuronal hyperpolarization by activating potassium”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.2. Xenon gas (NBTX-001)
What the sources say
- Not checked yetcites Zhou, Liu, & Chen, 2012
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, treatment with xenon has been shown to decrease pro-inflammatory cytokine levels, including TNFα and IL1β, and to upregulate growth factors such as BDNF [for details and references, see (Dobrovolsky, Ichim, Ma, Kesari, & Bogin, 2017)].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.2. Xenon gas (NBTX-001)
What the sources say
- Not checked yetcites Dobrovolsky, Ichim, Ma, Kesari, & Bogin, 2017
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CB1 is densely expressed in brain areas relevant to anxiety and is the main eCB receptor to which AEA and 2-AG bind, mediating the many behavioural and brain functions of eCB (Patel et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2. Endocannabinoid system
What the sources say
- Not checked yetcites Patel et al., 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a recently published open-label study involving 80 patients with diagnosed PD, the sub-chronic inhalation of sub-anaesthetic concentrations of a xenon-oxygen mixture immediately and progressively reduced the occurrence of panic attacks as well as of anxiety in general, and this reduction lasted up to 6 months after treatment (Dobrovolsky et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.1.2. Xenon gas (NBTX-001)
What the sources say
- Not checked yetcites Dobrovolsky et al., 2017 source
plaindirectn = 80- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It acts as negative allosteric modulator at the CB 1 receptor -explaining the lack of CB1-associated psychotropic effects -and as a partial agonist at the 5HT1A receptor which seem to be important for its anxiolytic and anti-panic effects.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.1. Cannabis
What the sources say
- Not checked yetcites Crippa, Guimaraes, Campos, & Zuardi, 2018
- Not checked yetcites Soares & Campos, 2017
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Enhanced eCB signallingfor example, induced by blocking the serine hydrolase enzyme FAAHreduces stress and anxiety responses and promotes fear-extinction learning (Gunduz-Cinar, Hill, McEwen, & Holmes, 2013;Lisboa et al., 2019;Mayo et al., 2019;Patel et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2. Endocannabinoid system
What the sources say
- Not checked yetcites Gunduz-Cinar, Hill, McEwen, & Holmes, 2013
- Not checked yetcites Lisboa et al., 2019 source
- Not checked yetcites Mayo et al., 2019
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, cannabis use itself can increase the risk for the onset of anxiety disorders, with greater symptom severity and with poorer treatment outcome [ (Grunberg, Cordova, Bidwell, & Ito, 2015;Mammen et al., 2018;Zvolensky et al., 2006), but see (Feingold, Rehm, Factor, Redler, & Lev-Ran, 2018)].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.1. Cannabis
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This is an important question as low doses of THC are anxiolytic and high doses of THC are arousing and anxiogenic, and CBD is able to block the anxiogenic effects of THC (Kamal, Kamal, & Lantela, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.1. Cannabis
What the sources say
- Not checked yetcites Kamal, Kamal, & Lantela, 2018
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CBD, which has anticonvulsant, antipsychotic and muscle-relaxant properties, but lacks the psychoactive and 'high-inducing' effects of THC, attenuates anxiety measures and autonomic arousal as well as the activation of the amygdala and the anterior cingulate cortex in response to fearful faces in healthy volunteers (Rabinak & Phan, 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.1. Cannabis
What the sources say
- Not checked yetcites Rabinak & Phan, 2014
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In treatment-naïve patients with generalised SAD a single dose of CBD was found to significantly reduce anxiety and associated anticipatory alert, as well as discomfort provoked during a public-speaking test (Bergamaschi et al., 2011;Crippa et al., 2011).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.1. Cannabis
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, a destabilising polymorphism in the FAAH gene causes increased AEA levels and is associated with lower indices of trait anxiety as well as with enhanced cortico-amygdala connectivity and reduced amygdala activation in response to threat stimuli (Patel et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.2. FAAH inhibitors
What the sources say
- Not checked yetcites Patel et al., 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, plasma vasopressin levels are elevated in patients with PTSD (de Kloet, Vermetten, Geuze, Wiegant, & Westenberg, 2008) and with OCD (Altemus, Cizza, & Gold, 1992).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.1. Vasopressin system: SRX246
What the sources say
- Not checked yetcites de Kloet, Vermetten, Geuze, Wiegant, & Westenberg, 2008
- Not checked yetcites Altemus, Cizza, & Gold, 1992
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Its central actions are mediated by binding to the two G-protein coupled V 1A and V 1B receptors which are distributed in many anxiety-and fear-related brain areas including in the lateral septum, cortex and hippocampus, with V 1A receptors being the predominant receptor (Landgraf, 2006).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.1. Vasopressin system: SRX246
What the sources say
- Not checked yetcites Landgraf, 2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, genetic and epigenetic variations in the OXT receptor gene have been associated with alterations in socio-emotionality and, in part, with increased stress responses (Naja & Aoun, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.2. Oxytocin system
What the sources say
- Not checked yetcites Naja & Aoun, 2017
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“and attenuated amygdala activation in response to angry faces (Fig. 3) and vasopressin administration indicating a role of amygdalar V 1A receptors in the processing of aversive emotional information (Lee et al., 2013).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.1. Vasopressin system: SRX246
What the sources say
- Not checked yetcites Lee et al., 2013 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“As a result of these actions OXT treatment decreases amygdala activity in response to negative/ fearful emotions (Fig. 3) and increases the activity of cortical and subcortical regions, often in a sex-specific way (Gao et al., 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.2. Oxytocin system
What the sources say
- Not checked yetcites Gao et al., 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“NPY is the most abundant neuropeptide in the brain, acting via at least five different G-protein coupled receptors (Y 1 , Y 2 , Y 4-6 ) (Reichmann & Holzer, 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Reichmann & Holzer, 2016
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“From animal studies it is known that NPY mediates anxiolysis e.g. by inhibiting amygdalar activation and increasing calcineurin-induced synaptic remodelling in the basolateral amygdala (via the Y 1 receptor), counteracting the anxiogenic effect of CRH, reducing noradrenergic activity in the locus coeruleus and inhibiting excitatory neurotransmission in the dorsal periaqueductal grey (Kask et al.,”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Kask et al., 2002 source
- Not checked yetcites Reichmann & Holzer, 2016
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Elaborate preclinical studies showing that the overactivation of CRHR 1 by CRH drives the stress system and anxiety-related behaviours, have triggered the development of a number of non-peptidergic, orally available and brain-penetrating CRHR1 antagonists (Holsboer, 2001;Zorrilla & Koob, 2010).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Holsboer, 2001 source
- Not checked yetcites Zorrilla & Koob, 2010
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, since monotherapy with CRHR 1 receptor antagonists including verucerfont (GSK-561679, NBI-77860), R121919 (NBI-30775) and pexacerfont (BMS-562086) does not exhibit greater efficacy than placebo for the treatment of PTSD (Dunlop et al., 2017), GAD, SAD and major depressive disorder, despite good tolerability of these drugs in all of these clinical trials (Griebel & Holsboer, 2012),”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Dunlop et al., 2017 source
- Not checked yetcites Griebel & Holsboer, 2012
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, activation of the orexin system has been shown to be involved in the expression and consolidation of fear while it counteracts fear extinction (Flores et al., 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.3. Orexin system
What the sources say
- Not checked yetcites Flores et al., 2015 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Finally, NPS is a more recently characterized neuropeptide that exerts anxiolytic and arousal/activity promoting effects, and has been shown to enhance extinction learning-[for recent review, see (Grund & Neumann, 2019)].”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Grund & Neumann, 2019
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“After the latest disappointing clinical trials, verucerfont has disappeared from the product pipeline of Neurocrine Biosciences for PTSD, but remains a treatment for congenital adrenal hyperplasia (https://www.neurocrine.com/pipeline/ pipeline-overview/).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites https://www.neurocrine.com/pipeline/ pipeline-overview/
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“It is a voltagesensitive sodium channel blocker with high affinity for inactivated channels resulting in the inhibition of high-frequency neuronal firing.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.4. Voltage-gated ion channels 6.4.1. Riluzole and Troriluzole
What the sources say
- Not checked yetcites Bellingham, 2011 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“As a proposed main mechanism, riluzole reduces glutamatergic neurotransmission by blocking NMDA receptors, increasing synaptic AMPA receptor trafficking and the clearance of glutamate via glutamate transporters.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.4. Voltage-gated ion channels 6.4.1. Riluzole and Troriluzole
What the sources say
- Not checked yetcites Bellingham, 2011 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The potential of the NPS system as a novel anxiolytic target is supported by studies in humans showing that a polymorphism in the NPS receptor gene, resulting in an amino acid exchange of asparagine to isoleucine (A/T) at position 107 and a more functional variant, is associated with PD and distorted cortico-limbic activity during emotion processing in healthy adults and PD patients, as well as”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.3.4. Other neuropeptide systems
What the sources say
- Not checked yetcites Grund & Neumann, 2019
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, it has been shown to improve anxiety symptoms in patients with diagnosed major depressive disorder when given alone or in combination with standard antidepressant treatment (Sanacora, Kendell, Fenton, Coric, & Krystal, 2004), although the newest study was not able to reproduce this effect (Mathew, Gueorguieva, Brandt, Fava, & Sanacora, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.4. Voltage-gated ion channels 6.4.1. Riluzole and Troriluzole
What the sources say
- Not checked yetcites Sanacora, Kendell, Fenton, Coric, & Krystal, 2004
- Not checked yetcites Mathew, Gueorguieva, Brandt, Fava, & Sanacora, 2017
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Of these, kavain and dihydrokavain have the strongest anxiolytic potential, thought to be mediated via the positive allosteric modulation of BDZ-sensitive and -insensitive forms of GABA-A receptors (Chua et al., 2016).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7.1. Kava
What the sources say
- Not checked yetcites Chua et al., 2016 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In rodents, a single dose of riluzole produces clear anxiolytic effects in a dose-dependent manner (Sugiyama et al., 2012) without evidence of oversedation, amnesia or coordinative problems as seen with BDZs.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.4. Voltage-gated ion channels 6.4.1. Riluzole and Troriluzole
What the sources say
- Not checked yetcites Sugiyama et al., 2012 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Kava does not elicit acute anxiolysis comparable to a BDZ, but reduces anxiety measures within a week of treatment (Gastpar & Klimm, 2003;Volz & Kieser, 1997).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7.1. Kava
What the sources say
- Not checked yetcites Gastpar & Klimm, 2003
- Not checked yetcites Volz & Kieser, 1997
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“While several classes of phytochemicals are already considered in cases of mild anxiety or as supplements to conventional anxiolytic therapies, the anxiolytic effects of phytochemicals have been demonstrated predominantly in studies involving animal models (Fedotova et al., 2017), and the structure-activity relationships, metabolism, absorption and neuropharmacological mechanisms are not clear in”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7. Phytochemicals
What the sources say
- Not checked yetcites Fedotova et al., 2017 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Nevertheless, a recent meta-analysis revealed that the current evidence is promising, but still insufficient to support claims of superior effectiveness of kava over placebo in GAD (Ooi, Henderson, & Pak, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7.1. Kava
What the sources say
- Not checked yetcites Ooi, Henderson, & Pak, 2018
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“So far, a systematic review supports the use of kava for the short-term treatment (up to eight weeks) of anxiety, but points out that it is not a replacement for prolonged anti-anxiety drug use (Smith & Leiras, 2018).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7.1. Kava
What the sources say
- Not checked yetcites Smith & Leiras, 2018
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This approach, however, does not seem to provide consistently superior benefits across anxiety disorders, but may be useful for those patient groups that do not adequately respond to CBT alone (Etkin et al., 2019;Tolin, 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8. Pharmacological augmentation of psychotherapy
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Psychotherapeutic programmes are often insufficiently available, time-consuming and require extensive training of the therapist.
None of the sources cited for this claim have been checked yet.
In the paper
“It was reported that the standardised extract containing 0.374 mg of Galphimine-B per dose demonstrated similar efficacy in reducing anxiety, but better tolerability after four and 10 weeks of treatment as compared with the active comparators lorazepam and alprazolam (Herrera-Arellano et al., 2007;Romero-Cerecero et al., 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7.2. Other plants in clinical development
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It was found that chamomile was safe and efficacious in reducing anxiety symptoms in moderate GAD cases, but did not affect the rate of relapse.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 7.2. Other plants in clinical development
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While DCS is not anxiolytic per se, it has been shown to facilitate fear extinction in rodents although fear recovery was still seen under certain conditions following cycloserine-promoted extinction (Richardson, Ledgerwood, & Cranney, 2004;Walker, Ressler, Lu, & Davis, 2002).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.1. Facilitating fear-extinction mechanisms
What the sources say
- Not checked yetcites Richardson, Ledgerwood, & Cranney, 2004
- Not checked yetcites Walker, Ressler, Lu, & Davis, 2002
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, CBT is not efficacious or acceptable for all patients, as demonstrated by considerable rates of partial or non-response (the mean rate is 35-54% in meta-analyses) as well as of non-adherence (Loerinc et al., 2015;Taylor et al., 2012).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8. Pharmacological augmentation of psychotherapy
What the sources say
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Psychotherapeutic programmes are often insufficiently available, time-consuming and require extensive training of the therapist.
In the paper
“Mounting preclinical data demonstrate that activation of the eCB system using FAAH and MAG-L inhibitors or CB 1 receptor agonists enhances fear extinction while its pharmacological or genetic inactivation impairs fear extinction (Patel et al., 2017).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.1. Facilitating fear-extinction mechanisms
What the sources say
- Not checked yetcites Patel et al., 2017 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, boosting dopamine signalling with systemic administration of the dopamine bioprecursor L-3,4dihydroxyphenylalanine (L-DOPA) accelerates fear extinction and reduces fear relapse in humans (Gerlicher, Tuscher, & Kalisch, 2018;Haaker et al., 2013), in particular in conditions when low fear is displayed at the end of the extinction session (Gerlicher, Tuscher, & Kalisch, 2019).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.1. Facilitating fear-extinction mechanisms
What the sources say
- Not checked yetcites Gerlicher, Tuscher, & Kalisch, 2018
- Not checked yetcites Haaker et al., 2013
- Not checked yetcites Gerlicher, Tuscher, & Kalisch, 2019
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Both drugs are agonists at 5-HT 1A , 5-HT 2A and 5-HT 2C receptors with varying affinities, whereby the full or partial agonism at the 5-HT 2A receptor is likely to be the necessary site of action for eliciting an altered state consciousness including prosocial and pro-cognitive effects.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Liechti, 2017 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Beneficial effects of combining propranolol with trauma reactivation have been reported in a recent small randomised controlled trial (Brunet et al., 2018) as well as in three earlier pilot studies (Brunet et al., 2008;Pitman et al., 2002;Vaiva et al., 2003); however, negative outcomes have also been reported (Hoge et al., 2012;Wood et al., 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.2. Targeting fear-memory-(re)consolidation mechanisms
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the use of a single dose of either LSD or psilocybin in a controlled clinical setting can considerably improve the quality of life of patients in parallel with relatively few side effects and a low prevalence of abuse”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Likewise, modest to high doses of psilocybin have been shown to rapidly reduce clinical signs of anxiety and depression in cancer patients (Griffiths et al., 2016;Ross et al., 2016) and in patients with treatment-resistant depression (Carhart-Harris et al., 2016) receiving psychotherapeutic support for up to six months.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Propranolol is the most widely studied compound in regard to both the potential blocking of memory consolidation following trauma (Amos, Stein, & Ipser, 2014) and the interference with reconsolidation mechanisms.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.2. Targeting fear-memory-(re)consolidation mechanisms
What the sources say
- Not checked yetcites Amos, Stein, & Ipser, 2014
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, pharmacological strategies for interfering with fear reconsolidation appear to be viable, but data are insufficient and variable, and thus do not support their clinical application at present.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.2. Targeting fear-memory-(re)consolidation mechanisms
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It should be noted that the mechanism(s) of the acute anxiolytic effects of LSD, psilocybin and MDMA are not clear, but are thought to involve common changes in the functional connectivity of key substrates of the anxiety/fear neurocircuitries (Carhart-Harris & Nutt, 2017) and attenuated reactivity of the amygdala (Grimm, Kraehenmann, Preller, Seifritz, & Vollenweider, 2018;Kraehenmann et al., 201”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 8.3. Improving adherence to psychotherapy
What the sources say
- Not checked yetcites Carhart-Harris & Nutt, 2017
- Not checked yetcites Grimm, Kraehenmann, Preller, Seifritz, & Vollenweider, 2018
- Not checked yetcites Kraehenmann et al., 2015 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Such promising novel candidates include ketamine, riluzole and xenon, all modulating glutamatergic neurotransmission.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“While ketamine and xenon inhibit NMDA receptors, riluzole and its prodrug troriluzole increase the clearance of glutamate and decrease glutamate release.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Among those drugs, DCS is the most studied and is an example of successful research from bench to bedside, with promising outcomes in some clinical studies and specific anxiety disorders, but also negative results in others.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Conclusions derived from these studies have retrospectively helped to refine DCS-assisted EBT and are guiding the development of other candidates to facilitate fear-inhibitory learning, such as MDMA and L-DOPA.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Many of these new treatments have not been yet sufficiently clinically investigated in terms of their long-term safety, and there are concerns about the risk of dependence with the above-mentioned psychedelics, but also with the use of ketamine, MDMA, medicinal cannabis/marijuana and synthetic cannabinoids.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Drug-induced relief in anxiety-related symptoms can be immediate (acute) or delayed requiring repeated treatment.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.3. Drug discovery process refinements
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“polypharmacy, that is widely used in the clinical/outpatient setting with the risk of more and/or more severe side effects due to drug-drug interactions.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“multi-target drugs address several biological targets and may either treat two aspects of the disease (e.g.propranolol reduces somatic symptoms and interferes with fear re-consolidation in PTSD patients, see Section 8) or produce additive and even synergistic effects.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“polymorphisms in the 5-HT transporter, as well as in the 5-HT 1A , 5-HT 2A and 5-HT 3 receptors, have been reported in different anxiety disorders, likely influencing the efficacy of 5-HT-based pharmacotherapy (Helton & Lohoff, 2015).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.1. Biomarkers and personalized treatment
What the sources say
- Not checked yetcites Helton & Lohoff, 2015
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The shift in drug discovery to multi-target approaches is also increasingly being promoted in other CNS research areas, such as neurodegenerative disorders (Anighoro, Bajorath, & Rastelli, 2014;Ramsay, Popovic-Nikolic, Nikolic, Uliassi, & Bolognesi, 2018;Zheng, Fridkin, & Youdim, 2014).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
What the sources say
- Not checked yetcites Anighoro, Bajorath, & Rastelli, 2014
- Not checked yetcites Ramsay, Popovic-Nikolic, Nikolic, Uliassi, & Bolognesi, 2018
- Not checked yetcites Zheng, Fridkin, & Youdim, 2014
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“anxiety patients display changes in processing of information in relevant neuronal pathways and networks which will be further characterized using novel methods (see e.g.(Yang et al., 2019) and show sensitivity to existing anxiolytic treatments.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.2. Circuit level approaches
What the sources say
- Not checked yetcites Yang et al., 2019
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“anxiety disorders are polygenetic and associated with disturbances in multiple complex neuronal systems (Bandelow et al., 2016;Millan, 2003).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
What the sources say
- Not checked yetcites Bandelow et al., 2016
- Not checked yetcites Millan, 2003
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The onset of therapeutic action of antidepressants is delayed for 2-3 weeks or more.
“The onset of therapeutic action is delayed for 2-3 weeks or more, therefore antidepressants cannot be used as an acute anxiolytic intervention.”
The paper relies on this without support.
Duloxetine and pregabalin were approved by FDA and/or EMA for GAD in 2006/07.
“In 2006/07, the two latest anxiolytic drugs, duloxetine and pregabalin, were approved by the Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA) for the treatment of GAD (Fig. 1).”
The paper relies on this without support.
Anxiety symptoms are typically core features of all anxiety-related disorders and they have in part overlapping neurobiological mechanisms.
“Considering that anxiety symptoms are typically core features of all of these disorders and they have in part overlapping neurobiological mechanisms, the drug development for anxiety disorders, PTSD and OCD is discussed jointly in this review and the used term anxiety and related disorders includes all of these disorders.”
The paper relies on this without support.
Anxiety disorders are multifactorial in cause, involving an interaction between multiple genetic and environmental factors.
“Family and twin studies have indicated that anxiety disorders are multifactorial in cause, involving an interaction between multiple genetic and environmental factors.”
The paper relies on this without support.
Current approaches such as antidepressants or CBT produce plastic changes after chronic treatment only.
“Current approaches such as antidepressants or CBT produce plastic changes after chronic treatment only.”
The paper relies on this without support.
Levels of inborn anxiety-related behaviour and sensitivity to anxiolytics can differ greatly between mouse strains, but this fact is scarcely taken into consideration in preclinical studies exploring the anxiolytic properties of novel drugs.
“Moreover, although levels of inborn anxiety-related behaviour and sensitivity to anxiolytics can differ greatly between mouse strains, this fact is scarcely taken into consideration in preclinical studies exploring the anxiolytic properties of novel drugs.”
The paper relies on this without support.
Some brain areas such as BNST, amygdala, and PFC are partitioned into subregions that can mediate distinct and sometimes even opposite functions.
“Some of the brain areas such as the BNST, amygdala, and PFC are partitioned into subregions that can mediate distinct and sometimes even opposite functions (e.g.anxiogenic vs. anxiolytic).”
The paper relies on this without support.
Preclinical findings in animal models of anxiety predict anxiolytic efficacy in humans.
“preclinical evidence of anxiolytic and antidepressant properties has stimulated further investigation for its use in GAD and major depression as well as for schizophrenia and multiple sclerosis (Ivachtchenko, Lavrovsky, & Okun, 2016).”
The paper relies on this without support.
Findings and treatments for one anxiety disorder generalize to other anxiety disorders.
“it is likely to be particularly useful for anxiety patient populations with sleep-related symptoms including also PTSD and OCD (De Berardis et al., 2015).”
The paper relies on this without support.
TSPO promotes endogenous neurosteroidogenesis by supplying cholesterol to the cytochrome P450 enzyme for conversion into pregnenolone.
“Ligands targeting the translocator protein (TSPO), which promotes the endogenous neurosteroidogenesis by supplying cholesterol to the cytochrome P450 enzyme for conversion into pregnenolone, have received particular interest.”
The paper relies on this without support.
Preclinical anxiolytic-like effects in animals predict clinical anxiolytic efficacy in humans.
“There is strong preclinical evidence that drugs reducing glutamatergic neurotransmission cause fast antidepressant and anxiolytic effects in animals and humans (Williams & Sanacora, 2015).”
The paper relies on this without support.
Mimicking or enhancing endogenous anxiety-reducing neuropeptide systems will produce clinical anxiolysis with fewer side effects than traditional anxiety medications.
“Specifically, neuropeptides such as neuropeptide S (NPS), neuropeptide Y (NPY), oxytocin (OXT) and others can act as natural anxiety-reducing molecules, and therefore mimicking their effect or enhancing their endogenous action would potentially produce anxiolysis with fewer side effects than traditional anxiety medications.”
The paper relies on this without support.
Aloradine has so far shown a side-effect profile similar to placebo.
“Given that aloradine, so far, has shown a side-effect profile similar to placebo, the follow-up multi-centre Phase 3 trial launched by VistaGen in 2019 will be of considerable interest.”
The paper relies on this without support.
In animal studies, substance P modulates anxiety-related behaviour via its three neurokinin receptors.
“In animal studies, substance P modulates anxiety-related behaviour via its three neurokinin receptors.”
The paper relies on this without support.
Psychotherapeutic programmes are often insufficiently available, time-consuming and require extensive training of the therapist.
“The disadvantage of psychotherapeutic programmes is that apart from the fact that they are often insufficiently available, they are time-consuming and require extensive training of the therapist.”
The paper relies on this without support.
Safety concerns around long-term consumption of kava remain.
“Although the ban by some European countries at the beginning of the 21st century on kava products for human consumption due to cases of hepatotoxicity has subsequently been lifted, e.g. in Germany, safety concerns around long-term consumption of kava remain.”
The paper relies on this without support.
After pregabalin and duloxetine were last approved for GAD in 2006 and 2007, no other drug was successful in completing clinical development for anxiety and related disorders.
“After pregabalin and duloxetine were last approved for the treatment of GAD in 2006 and 2007, respectively, no other drug was successful in completing clinical development for the treatment of anxiety and related disorders.”
The paper relies on this without support.
Anxiety and related disorders are the most prevalent mental disorders.
“the most prevalent mental disorders”
The paper relies on this without support.
Current first-line treatments are ineffective for a considerable proportion of patients.
“The finding that current first line treatments proved ineffective for a considerable proportion of patients indicates the need to change treatment strategies”
The paper relies on this without support.
Heterogeneity within anxiety disorders and inaccurate subgroup stratification tools have hampered development of novel anxiolytic drugs with improved treatment outcome.
“Problems associated with the heterogeneity within a given anxiety disorder as classified presently, together with inaccurate subgroup stratification tools have likely hampered the development of novel anxiolytic drugs with improved treatment outcome.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“As pharmacology-based and psychotherapy-based interventions are independently capable of modulating circuit-level neural activity, pharmacologically-enhanced psychotherapy would seem an obvious opportunity to target specific circuits more effectively and potentially reduce the need for chronic pharmacological therapy [58].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [58]
In the citing paper
“Promising results have been obtained by enhancing psychotherapy with methylenedioxymethamphetamine (MDMA; phase three clinical trial NCT03537014 is currently assessing MDMA-assisted psychotherapy for PTSD), oxytocin [59], L-DOPA [60], and other compounds (for review, see [58]).”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [58]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
“Regarding the cannabinoid system, randomised clinical trials, although limited in number, have revealed promising evidence of rapidly reducing anxiety symptoms through CB 1 receptor activation by natural or synthetic cannabinoids or the use of FAAH inhibitors including JNJ-42165279.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.2. FAAH inhibitors
“while a Phase 2 randomised clinical trial investigating its efficacy in patients with SAD (NCT02432703) was completed in October 2018, though no results are available yet.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 9. Summary and conclusion
“The rapid-acting synthetic neurosteroid aloradine is an example of a refined agent targeting GABAergic mechanisms via the GABA-A receptor and represents a novel drug for on-demand treatment of SAD.”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 5.2.2. Neurosteroids
“Aloradine does not bind to monoaminergic, glutamatergic, peptidergic, opioid, glucocorticoid or sex-hormone receptors (Liebowitz et al., 2016) and it is not clear whether it targets the GABA-A receptor.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.3. Drug discovery process refinements
“| Gepirone ER | Travivo® | Fabre-Kramer | 5-HT 1A PAG | | 3 | GAD | https://www.fabrekramer. | |”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.3. Drug discovery process refinements
“| GAD | Cannabidiol | AVN-101 | | | | Troriluzole | FKW00GA | | | | Vilazodone | Gepirone ER | |”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.3. Drug discovery process refinements
“| Brexpiprazole | | Otsuka | PAG: 5-HT 1A , D 2 , 3 , ANTG: 5-HT 2A , 7, α 1B,2C N | MDD, schizophrenia | 2 | PTSD | NCT03033069 | Completed in |”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.3. Drug discovery process refinements
“| PTSD | Brexpiprazole | Cannabidiol | Lanicemine |”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 6.2.1. Cannabis
“The first clinical trials evaluating the effects of nabilone (Phase 1) or marijuana (Phase 2) in OCD are currently ongoing (Table 2).”
§ Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders > 10.3. Drug discovery process refinements
“| | | Nabilone | |”
Citations
Cites
1 retracted
Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., Hamilton, S., Yazar-Klosinski, B., Emerson, A., & Doblin, R. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05249-5 · Cited by 359
RetractedKyu, H. H., Abate, D., Abate, K. H., Abay, S. M., Abbafati, C., Abbasi, N., Abbastabar, H., Abd-Allah, F., Abdela, J., Abdelalim, A., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)32335-3 · Cited by 4,192
Etkin, A., & Wager, T. D. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07030504 · Cited by 3,391
Maximizing exposure therapy: An inhibitory learning approach
Craske, M. G., Treanor, M., Conway, C. C., Zbozinek, T., & Vervliet, B. (2014) · Behaviour Research and Therapy · doi:10.1016/j.brat.2014.04.006 · Cited by 2,339
Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., & Klinedinst, M. A. (2016) · Journal of Psychopharmacology · doi:10.1177/0269881116675513 · Cited by 2,201
Cannabinoids for Medical Use: A Systematic Review and Meta-analysis
Whiting, P. F., Wolff, R. F., Deshpande, S., Di Nisio, M., Duffy, S., Hernandez, A. V., Keurentjes, J. C., Lang, S., Misso, K., Ryder, S., et al. (2015) · JAMA · doi:10.1001/jama.2015.6358 · Cited by 2,169
A Historical Overview of Natural Products in Drug Discovery
Dias, D. A., Urban, S., & Roessner, U. (2012) · Metabolites · doi:10.3390/metabo2020303 · Cited by 2,106
The Neurocircuitry of Fear, Stress, and Anxiety Disorders
Shin, L. M., & Liberzon, I. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.83 · Cited by 2,083
Epidemiology of anxiety disorders in the 21st century
Bandelow, B., & Michaelis, S. (2015) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2015.17.3/bbandelow · Cited by 2,079
Neuronal circuits for fear and anxiety
Tovote, P., Fadok, J. P., & Lüthi, A. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3945 · Cited by 1,786
Research works printed but not linked: 3
- Anonymous, 2018, Drug and device news, Pharmacy Therapeutics, 43, 74
- Pittler, 2003, Kava extract for treating anxiety, Cochrane Database of Systematic Reviews, CD003383
- Sullivan, 2018, Time since trauma in PTSD: Phase 3 multi-center, double-blind, placebo-controlled trial of TNX-102 SL, a sublingual formualtion of cyclopbenzaprine, in military-RElated PTSD (study TNX-CY-P301), Innoations in Clincial Neuroscience, 15, S10
Cited by
Sorted by citations
Epidemiology of anxiety disorders: global burden and sociodemographic associations
Javaid, S. F., Hashim, I. J., Hashim, M. J., Stip, É., Samad, A., & Ahbabi, A. A. (2023) · Middle East Current Psychiatry · doi:10.1186/s43045-023-00315-3 · Cited by 565
“In recent decades, there has been increased knowledge of the causes of anxiety disorders, enhanced preventive measures, and greater access to proactive mental health care services [9, 13, 24].”
BackgroundPharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options
Garakani, A., Murrough, J. W., Freire, R. C., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.595584 · Cited by 440
“The European Union has similar indications for the use of SSRIs and SNRIs for the treatment of anxiety disorders as the FDA but with broader indications of SSRIs (12).”
BackgroundCimino, C., Maurel, O. M., Musumeci, T., Bonaccorso, A., Drago, F., Souto, E. B., Pignatello, R., & Carbone, C. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13030327 · Cited by 343
Chugh, V., Krishna, K. V., & Pandit, A. S. (2021) · ACS Nano · doi:10.1021/acsnano.1c03800 · Cited by 219
Bandelow, B., Allgulander, C., Baldwin, D. S., Costa, D. L. D. C., Denys, D., Dilbaz, N., Domschke, K., Eriksson, E., Fineberg, N. A., Hättenschwiler, J., et al. (2023) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2022.2086295 · Cited by 158
“glutamate receptor agonists and antagonists, neuropeptide Y agonists, CRH receptor antagonists, GABA-A sub-unit selective ligands, natriuretic peptide, cannabinoids, and nitroflavanoids (Sartori and Singewald 2019; Bandelow 2020).”
Background
Metadata
- Authors
- Sartori, S. B., & Singewald, N.
- Affiliations
- Universität Innsbruck (AT)
- Corresponding author
- Singewald, Nicolas
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 204
- Pages
- 107402
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W2970453706
- Semantic Scholar
- 4797d7c796f1e05cba4c8ad314f35e67a58995c0
- Cited by
- 236
- References
- 460
- Citations by year
- 2026: 10 · 2025: 29 · 2024: 65 · 2023: 41 · 2022: 33 · 2021: 38 · 2020: 18 · 2019: 2
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Pharmacology & Therapeutics (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund (DK W-1206, SFB F4410, I2433-B26)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- anxiety disorders, anxiolytic drug development, therapeutic target, fear extinction, glutamatergic neurotransmission, ketamine, riluzole, xenon, neurosteroids, D-cycloserine, MDMA, L-DOPA, cannabinoids, endocannabinoid system, neuropeptides, ion channels, phytochemicals, benzodiazepines, serotonergic system, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder
- MeSH terms
- Animals, Anxiety Disorders, Humans, Anti-Anxiety Agents, Molecular Targeted Therapy
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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