The DOI matches its Crossref record; 223 of the 227 references it cites were found in a registry or an index; 119 of the 231 sources its claims cite were checked for support.
Ketamine in neuropsychiatric disorders: an update
Open accessAbstract
The discovery of ketamine as a rapid-acting antidepressant led to a new era in the development of neuropsychiatric therapeutics, one characterized by an antidepressant response that occurred within hours or days rather than weeks or months. Considerable clinical research supports the use of-or further research with-subanesthetic-dose ketamine and its (S)-enantiomer esketamine in multiple neuropsychiatric disorders including depression, bipolar disorder, anxiety spectrum disorders, substance use disorders, and eating disorders, as well as for the management of chronic pain. In addition, ketamine often effectively targets symptom domains associated with multiple disorders, such as anxiety, anhedonia, and suicidal ideation. This manuscript: 1) reviews the literature on the pharmacology and hypothesized mechanisms of subanesthetic-dose ketamine in clinical research; 2) describes similarities and differences in the mechanism of action and antidepressant efficacy between racemic ketamine, its (S) and (R) enantiomers, and its hydroxynorketamine (HNK) metabolite; 3) discusses the day-to-day use of ketamine in the clinical setting; 4) provides an overview of ketamine use in other psychiatric disorders and depression-related comorbidities (e.g., suicidal ideation); and 5) provides insights into the mechanisms of ketamine and therapeutic response gleaned from the study of other novel therapeutics and neuroimaging modalities.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This narrative review updates the evidence for subanesthetic ketamine and esketamine across neuropsychiatric disorders, emphasizing rapid antidepressant and transdiagnostic effects alongside mechanistic and clinical-practice issues. It concludes that efficacy is broad but often supported by small or preliminary studies, with long-term safety and misuse data still limited.
Key findings
- Subanesthetic ketamine/esketamine can produce rapid effects in depression and bipolar disorder, often within hours, peaking near 24 h and declining over 10–12 days; intranasal esketamine received FDA approval for treatment-resistant depression in 2019 and for major depression with acute suicidal ideation or behavior in 2020.
- Real-world effectiveness estimates include a meta-analytic mean response rate of 55.3% and remission rate of 28.9%, community-practice response/remission of roughly 50%/30%, and 6-month intranasal esketamine response/remission of 47.8%/37%; a telehealth sublingual ketamine trial (n = 1247) reported PHQ-9 remission of 32.6% and GAD-7 remission of 31.3%.
- For suicidal ideation, meta-analyses show reductions from one day up to six weeks, partly independent of mood effects; one crossover trial (n = 37) found 69% complete remission after six infusions maintained with weekly maintenance, and an emergency-department RCT (n = 18) reported 88% remission between 90 and 180 min after treatment.
- Evidence in other conditions is mixed: a multicenter PTSD trial (n = 158) found no effect on PTSD symptoms despite reduced depressive symptoms; OCD trials are mostly positive but one open-label study (n = 10) found no OCD effect; alcohol-use trials suggest increased abstinence, while cocaine self-administration fell by 67% at 24 h but the effect faded; (R)-ketamine did not separate from placebo at 24 h in a Phase 2a trial (n = 102).
Methods
- Narrative review synthesizing pharmacology, hypothesized mechanisms, clinical use, and recent clinical findings (2019–2023) across psychiatric disorders, with Table 1 summarizing selected studies.
- Draws on preclinical work, meta-analyses, randomized controlled trials, open-label pilots, case series, and neuroimaging modalities including EEG, MEG, MRS, fMRI, and PET; neurological conditions such as Alzheimer’s, Huntington’s, and Parkinson’s disease are excluded.
- No primary data collection or formal systematic meta-analysis is reported.
Limitations
- The authors state that many trials are pilot studies or case series, often uncontrolled or with small samples, and that larger, more rigorous trials are needed; efficacy for several conditions rests on few trials and participants.
- The authors also note high placebo response rates in depression and suicidality research, outcome measures such as MADRS being designed for longer intervals than rapid-acting effects, and scarce long-term safety, relapse, and misuse-liability data.
- Evident from the text: as a narrative review without a systematic search or risk-of-bias assessment, study selection and synthesis may be non-exhaustive, and heterogeneity in dose, route, frequency, and formulation complicates comparisons.
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Claims the paper makes
86 No full text of the sources · 57 Partly supported · 40 Supported · 31 Own interpretation · 28 No basis given · 5 Sources not found · 4 Not checked yet · 2 Supported so far · 1 Not supported · 1 Couldn’t confirm · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“though there were only minor changes in ED-related symptomology [123]”
§ Ketamine in neuropsychiatric disorders: an update > Eating disorders
What the sources say
- Disputedcites [123] Schwartz T, Trunko ME, Feifel D, Lopez E, Peterson D, Frank GKW, et al. A longitudinal case series of IM ketamine for patients with severe and enduring eating disorders and comorbid treatment-resistant depression. Clin Case Rep. 2021;9:e03869. sourceExperimental — accuracy not yet measured
The Results describe mild or limited eating-disorder improvement in Cases 1 and 4, but the claim that changes were only minor across the case series conflicts with the Discussion (page unavailable). It reports robust, sustained improvements in relevant eating-disorder measures for Cases 1 and 2, and full remission of the eating disorder in Case 2. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
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.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Shortly thereafter, ketamine's robust antidepressant effects were confirmed in treatmentresistant depression (TRD) and bipolar disorder (BD) [5][6][7]”
§ Ketamine in neuropsychiatric disorders: an update > INTRODUCTION
What the sources say
- Supportedcites [5] Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, et al. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry. 2010;67:793–802. source
This paper supports the bipolar-disorder part of the multi-citation sentence. In Abstract > Results, ketamine significantly improved depressive symptoms compared with placebo within 40 minutes in patients with treatment-resistant bipolar depression, with 71% responding to ketamine versus 6% to placebo at some point during the trial. The treatment-resistant major-depression part is covered by other citations, not attributed to this paper here. (LLM, conf=0.92)
- Supportedcites [6] Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry. 2012;71:939–46. source
The Introduction reports rapid antidepressant effects in treatment-resistant major depressive disorder from earlier trials. This paper's Results and Discussion report a robust, rapid response to ketamine versus placebo in patients with bipolar depression, replicating an earlier finding. (LLM, conf=0.92)
- Partly supportedcites [7] Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63:856–64. sourceExperimental — accuracy not yet measured
The COMMENT section reports a robust antidepressant response to ketamine in treatment-resistant depression. The PATIENT SELECTION section says patients with bipolar disorder were excluded, so this paper does not support the bipolar-disorder part of the sentence. (LLM, conf=0.91)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Ketamine then creates an open-channel block that prevents ions from traveling through the channel [17].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Partly supportedcites [17] Huettner JE, Bean BP. Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc Natl Acad Sci. 1988;85:1307–11. sourceExperimental — accuracy not yet measured
The introduction (page unavailable) identifies ketamine as an antagonist of NMDA responses, and the Discussion says it competes for the MK-801 binding site. But the Discussion's open, nonconducting channel model is for MK-801; our copy does not establish that ketamine itself produces an open-channel block that prevents ion flow. (LLM, conf=0.82)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“For instance, one trial found that remission rates post-ketamine were inferior to those post-ECT [69]”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Supportedcites [69] Eckstrand J, Fattah C, Persson M, Cheng T, Nordanskog P, Åkeson J, et al. Racemic ketamine as an alternative to electroconvulsive therapy for unipolar depression. A randomized, open-label, non-inferiority trial (KetECT). Int J Neuropsychopharmacol. 2022;25:339–49. source
The Results section (Primary Outcome: Remission Rates) reports remission in 46% of ketamine-treated patients versus 63% of ECT-treated patients, a statistically significant difference (P = .026). The Conclusion explicitly states that ECT was superior in remission rates. (LLM, conf=0.95)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Both theories converge on a downstream increase in αamino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) transmission, which activates cellular signaling pathways proposed to be integral to ketamine's rapid-acting therapeutic effects such as increases in BDNF expression and mechanistic target of rapamycin complex 1 (mTORC1) activation [28].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Supportedcites [28] Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018;23:801–11. source
The Conclusions describe interneuron-mediated disinhibition and direct (2R,6R)-HNK action as routes to AMPAR activation, followed by neuroplasticity-related signaling regulated by BDNF and mTORC1. The review presents these as proposed mechanisms of ketamine’s antidepressant effects, consistent with the citing sentence’s qualification. (LLM, conf=0.90)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“With regard to esketamine in particular, clinical use was largely based on four positive Phase 3 efficacy studies [62][63][64][65] that informed the subsequent FDA approval of intranasal esketamine for TRD and suicidal ideation with intent, as described above.”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Partly supportedcites [62] Daly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019;76:893–903. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports that this esketamine nasal-spray trial significantly delayed relapse in patients with treatment-resistant depression, supporting its identification as a positive efficacy study. The Study Population section (page unavailable) says current or recent suicidal ideation or intent was an exclusion criterion. Our copy does not establish that four studies informed FDA approval or that this trial supported approval for suicidal ideation with intent. (LLM, conf=0.86)
- Partly supportedcites [63] Fu D-J, Ionescu DF, Li X, Lane R, Lim P, Sanacora G, et al. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent: double-blind, randomized study (ASPIRE I). J Clin Psychiatry. 2020;81:19m13191. sourceExperimental — accuracy not yet measured
The Abstract (page not available) identifies this paper as the phase 3 ASPIRE I study and reports significantly greater improvement in depressive symptoms with esketamine. It can therefore support its place among the cited efficacy studies, but it does not establish that four studies informed FDA approval. The Clinical Points and Conclusions (pages not available) say that no medication was then approved for emergency treatment of depression with active suicidal ideation and intent; the paper reports approval for treatment-resistant depression only. (LLM, conf=0.86)
- Supportedcites [64] Ionescu DF, Fu D-J, Qiu X, Lane R, Lim P, Kasper S, et al. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: results of a Phase 3, double-blind, randomized study (ASPIRE II). Int J Neuropsychopharmacol. 2021;24:22–31. source
The Introduction identifies ASPIRE II as one of two phase 3 studies that formed the basis for the 2020 US approval to treat depressive symptoms in adults with MDD and acute suicidal ideation or behavior; it also notes the earlier approval for treatment-resistant depression. The Discussion reports that ASPIRE II improved depressive symptoms and was pivotal to the approval. This citation supports ASPIRE II’s role as one of the cited efficacy studies, rather than establishing the four-study count by itself. (LLM, conf=0.88)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, an inverse relationship was observed between (2S,6S;2R,6R)-HNK concentration and antidepressant response at three and seven days post-infusion; lower rather than higher levels of (2S,6S;2R,6R)-HNK were associated with improved response [47].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Partly supportedcites [47] Grunebaum MF, Galfalvy HC, Choo TH, Parris MS, Burke AK, Suckow RF, et al. Ketamine metabolite pilot study in a suicidal depression trial. J Psychiatr Res. 2019;117:129–34. sourceExperimental — accuracy not yet measured
The Results (Associations with 24h Post-Infusion Ratings) report that higher (2R,6R)-HNK levels correlated with less improvement in depressive symptoms at 24 hours. The Results (Associations with Weeks 1–6 Follow-up Ratings) report similar associations for the separately measured HNK enantiomers at certain weekly follow-ups. They do not report an association for combined (2S,6S;2R,6R)-HNK at three and seven days post-infusion. (LLM, conf=0.88)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“recent research suggests that (R)-ketamine and the ketamine metabolite (2R,6R)-HNK may exert antidepressant-like effects by upregulating AMPAR transmission independent of NMDAR antagonism [30,31].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Not checked — no full text of the sourcecites [30] Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, et al. Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms. Pharm Rev. 2018;70:621–60. source
- Partly supportedcites [31] Lumsden EW, Troppoli TA, Myers SJ, Zanos P, Aracava Y, Kehr J, et al. Antidepressant-relevant concentrations of the ketamine metabolite (2R,6R)-hydroxynorketamine do not block NMDA receptor function. Proc Natl Acad Sci USA. 2019;116:5160–69. sourceExperimental — accuracy not yet measured
The Discussion reports that (2R,6R)-HNK potentiates AMPAR-mediated transmission and that its antidepressant-relevant effects do not depend on direct NMDAR inhibition. It does not establish the same NMDAR-independent mechanism for (R)-ketamine: its comparisons concern ketamine without specifying that enantiomer, and it reports NMDAR inhibition by ketamine at antidepressant-relevant concentrations. Page numbers are not available in our copy. (LLM, conf=0.86)
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.
Every source the paper cites for this claim was checked and supports it.
In the paper
“This may be due to an increased incidence of adverse events in early-phase intranasal esketamine treatment; these decrease with subsequent treatments [39].”
§ Ketamine in neuropsychiatric disorders: an update > Depression and bipolar disorder
What the sources say
- Supportedcites [39] Williamson DJ, Gogate JP, Kern Sliwa JK, Manera LS, Preskorn SH, Winokur A, et al. Longitudinal course of adverse events with esketamine nasal spray: a post hoc analysis of pooled data from Phase 3 trials in patients with treatment-resistant depression. J Clin Psychiatry. 2022;83:21m14318. source
The Results report that the incidence of several adverse events was highest in week 1 and decreased thereafter. The Conclusions likewise state that adverse events generally become less frequent with ongoing treatment. The cited paper does not assess whether adverse events explain a greater number of treatments, but that explanation is the citing authors’ framing rather than the point directly attached to the citation. (LLM, conf=0.93)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Norketamine has also been investigated to a lesser extent [48] but, to date, no clinical trials have assessed its effects in MDD or BD.”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Partly supportedcites [48] Hashimoto K, Yang C. Is (S)-norketamine an alternative antidepressant for esketamine? Eur Arch Psychiatry Clin Neurosci. 2019;269:867–68. sourceExperimental — accuracy not yet measured
The main text (page unavailable) describes (S)-norketamine findings in rodent models and discusses its potential use in humans, supporting the point that clinical evidence remains limited. It does not explicitly state that no clinical trials have assessed norketamine in major depressive disorder or bipolar disorder. (LLM, conf=0.78)
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.
- Partly supported
- It may state two separate claims as one. 76
- Probably not a substantial claim. 29
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Ketamine is metabolized within minutes after administration by nitrogen-mediated demethylation to norketamine, mediated primarily by cytochrome P450 liver enzymes [18,19].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Partly supportedcites [18] Desta Z, Moaddel R, Ogburn ET, Xu C, Ramamoorthy A, Venkata SL, et al. Stereoselective and regiospecific hydroxylation of ketamine and norketamine. Xenobiotica. 2012;42:1076–87. sourceExperimental — accuracy not yet measured
The Introduction identifies N-demethylation to norketamine as a major ketamine metabolic pathway, and the Results identify CYP2B6 as its primary mediator in human liver microsomes. The cited passages do not establish that this conversion occurs within minutes after administration; the clinical observations concern later sampling times. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [19] Rao LK, Flaker AM, Friedel CC, Kharasch ED. Role of cytochrome P4502B6 polymorphisms in ketamine metabolism and clearance. Anesthesiology. 2016;125:1103–12. 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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“While dependence rates are relatively low amongst recreational users, long-term unregulated use has been reported to lead to issues such as ulcerative cystitis and memory impairment [11].”
§ Ketamine in neuropsychiatric disorders: an update > INTRODUCTION
What the sources say
- Supportedcites [11] Sassano-Higgins S, Baron D, Juarez G, Esmaili N, Gold M. A review of ketamine abuse and diversion. Depress Anxiety. 2016;33:718–27. source
The Global Use Patterns section says ketamine addiction appears low overall, consistent with the claim about relatively low dependence among recreational users. The Toxicity to the Urinary System section reports ulcerative cystitis in chronic users, and Long-Term Effects of Ketamine Use reports memory impairment. The copy provides no page numbers for these passages. (LLM, conf=0.88)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ketamine has been found to be effective for traditionally treatment-refractory symptoms such as suicidality, anxiety, and anhedonia, and to impact functional circuitries related to motivation [8,9].”
§ Ketamine in neuropsychiatric disorders: an update > INTRODUCTION
What the sources say
- Partly supportedcites [8] Monteggia LM, Zarate CAJ. Antidepressant actions of ketamine: from molecular mechanisms to clinical practice. Curr Opin Neurobiol. 2015;30:139–43. sourceExperimental — accuracy not yet measured
The Introduction (page not supplied) reports a rapid antidepressant response in treatment-resistant depression and rapid antisuicidal effects. It does not report efficacy for anxiety or anhedonia, or an effect on motivation-related functional circuits. (LLM, conf=0.86)
- Partly supportedcites [9] Mkrtchian A, Evans JW, Kraus C, Yuan P, Kadriu B, Nugent AC, et al. Ketamine modulates fronto-striatal circuitry in depressed and healthy individuals. Mol Psychiatry. 2021;26:3292–301. sourceExperimental — accuracy not yet measured
The Introduction describes anhedonia as a treatment-resistant depressive symptom that ketamine can improve. The Discussion reports improved anhedonia and altered fronto-striatal connectivity after ketamine in participants with treatment-resistant depression. Our copy does not establish ketamine’s effectiveness for suicidality or anxiety, so those parts of the attributed claim are unsupported. (LLM, conf=0.88)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The antidepressant effects of an acute dose of ketamine are typically thought to occur within hours, peak around 24 h then gradually decline over a period of 10-12 days [10].”
§ Ketamine in neuropsychiatric disorders: an update > INTRODUCTION
What the sources say
- Supportedcites [10] Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, et al. Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychol Med. 2016;46:1459–72. source
The Results (‘Change in depressive symptoms’; page not provided) report that a single ketamine infusion reduced depressive symptoms versus placebo within 40–60 minutes, peaked at day 1, and was no longer significantly superior by days 10–12. This supports the cited summary of the time course, though the reported findings concern patients with unipolar or bipolar depression in the pooled trials. (LLM, conf=0.91)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A large, randomized, controlled trial of 154 participants with TRD found that those who received an acute dose of ketamine (0.5 mg/kg) in conjunction with “automated selfassociation training” (ASAT) over four days had significantly reduced depression scores over a 30-day period; in contrast, the scores of those who received ketamine and a sham ASAT steadily increased over 30 days [56].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Supportedcites [56] Price RB, Spotts C, Panny B, Griffo A, Degutis M, Cruz N, et al. A novel, brief, fully automated intervention to extend the antidepressant effect of a single ketamine infusion: a randomized clinical trial. Am J Psychiatry. 2022;179:959–68. source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirectn = 154- 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“a recent, large, open-label effectiveness trial (n = 1247) found that sublingual ketamine monitored over telehealth applications was safe and effective for treating the symptoms of anxiety and depression [66]; 32.6% and 31.3% of participants were classified as remitted on the Patient Health Questionnaire 9 (PHQ-9) and the Generalized Anxiety Disorder 7-item Checklist (GAD-7), respectively.”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Partly supportedcites [66] Hull TD, Malgaroli M, Gazzaley A, Akiki TJ, Madan A, Vando L, et al. At-home, sublingual ketamine telehealth is a safe and effective treatment for moderate to severe anxiety and depression: findings from a large, prospective, open-label effectiveness trial. J Affect Disord. 2022;314:59–67. sourceExperimental — accuracy not yet measured
The Patients section reports 1,247 participants with sufficient follow-up data, and Table 2 reports remission rates of 32.6% on PHQ-9 and 31.3% on GAD-7 at session 4. The table calculates those rates from the participants with available session-4 scores (553 and 501, respectively), not from all 1,247 participants as the citing sentence could imply. The Background and Discussion describe the telehealth treatment and report low adverse-event rates. (LLM, conf=0.85)
plaindirectn = 1,247- 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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“One meta-analysis found that racemic ketamine elicited a greater overall antidepressant response and had fewer dropouts across studies than esketamine [36].”
§ Ketamine in neuropsychiatric disorders: an update > Depression and bipolar disorder
What the sources say
- Supportedcites [36] Bahji A, Vazquez GH. Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis. J Affect Disord. 2021;278:542–55. source
The Results (Moderator analyses; page not available) report greater overall antidepressant response with intravenous racemic ketamine than with intranasal esketamine, alongside fewer dropouts due to adverse events. This supports the cited summary, with the qualification that the Results specify adverse-event-related dropouts. (LLM, conf=0.92)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In addition to glutamatergic modulation, ketamine is also an opioid (mu, kappa, delta) and dopamine receptor agonist, inhibits monoamine reuptake, and antagonizes muscarinic receptors [32].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Partly supportedcites [32] Matveychuk D, Thomas RK, Swainson J, Khullar A, MacKay M-A, Baker GB, et al. Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers. Ther Adv Psychopharmacol. 2020;10:2045125320916657. sourceExperimental — accuracy not yet measured
The ‘Antidepressant mechanisms of ketamine and potential biochemical biomarkers’ section (page unavailable) lists opioid (mu, delta and kappa), monoaminergic, and muscarinic receptors or transporters as possible binding targets. It does not establish that ketamine is an opioid or dopamine receptor agonist, inhibits monoamine reuptake, or antagonizes muscarinic receptors; it describes the opioid system’s role as unclear and controversial. (LLM, conf=0.88)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, two studies (n = 134 and n = 157, respectively) found that intermittent low-dose ketamine (0.3 mg/kg, administered before each ECT treatment) improved cognitive functioning and reduced psychiatric complications after ECT [50,51].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not checked — no full text of the sourcecites [50] Dong J, Min S, Qiu H, Chen Q, Ren L. Intermittent administration of low dose ketamine can shorten the course of electroconvulsive therapy for depression and reduce complications: a randomized controlled trial. Psychiatry Res. 2019;281:112573. source
- Partly supportedcites [51] Zou W, Min S, Chen Q, Li X, Ren L. Subanesthetic dose of ketamine for the antidepressant effects and the associated cognitive impairments of electroconvulsive therapy in elderly patients—a randomized, double‐blind, controlled clinical study. Brain Behav. 2021;11:e01775. sourceExperimental — accuracy not yet measured
The Abstract Methods describe 157 enrolled elderly patients receiving 0.3 mg/kg ketamine with each ECT treatment. The Results (Cognitive impairments) report less cognitive impairment in the ketamine group during treatment, but no difference in MMSE scores at the end of ECT. The Results (Adverse events) report no significant reduction in psychiatric adverse events, so the claim about reduced psychiatric complications is unsupported. (LLM, conf=0.90)
plaindirectn = 134- 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 cited sources support only part of this claim — read each source’s verdict below.
In the paper
“research suggests that synaptic NMDAR transmission promotes cell survival and that extra-synaptic NMDARs promote cell death through p38MAPK inhibition and activation, respectively [25].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Partly supportedcites [25] Hardingham GE, Bading H. Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci. 2010;11:682–96. sourceExperimental — accuracy not yet measured
The ‘NMDAR paradox’ section says synaptic NMDAR signalling promotes neuronal survival whereas extrasynaptic signalling promotes death. ‘Calpain activation and STEP cleavage’ identifies p38 activation as an extrasynaptic pro-death pathway, but does not support synaptic p38 inhibition as the survival mechanism; it notes that neuroprotective synaptic activity can also activate p38. Page numbers were not available in our copy. (LLM, conf=0.88)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Preclinical research first suggested that metabolism to (2S,6S;2R,6R)-HNK was essential for ketamine's antidepressantlike effects and that (2R,6R)-HNK could exert its own antidepressant effects in mice [45,46].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Partly supportedcites [45] Zanos P, Highland JN, Liu X, Troppoli TA, Georgiou P, Lovett J, et al. (R)-Ketamine exerts antidepressant actions partly via conversion to (2R,6R)-hydroxynorketamine, while causing adverse effects at sub-anaesthetic doses. Br J Pharm. 2019;176:2573–92. sourceExperimental — accuracy not yet measured
The Introduction reports earlier preclinical evidence that conversion to (2S,6S;2R,6R)-HNK was necessary for ketamine’s full antidepressant-relevant effects in mice, and that (2R,6R)-HNK had antidepressant-like effects in animal tests. But “essential” overstates the first point: the Discussion concludes that conversion increases (R)-ketamine’s potency, while also describing effects independent of the metabolite. (LLM, conf=0.88)
- Supportedcites [46] Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016;533:481–6. source
In “Antidepressant actions of HNK” (Fig. 2i–l), the paper reports that hindering conversion to (2S,6S;2R,6R)-HNK eliminated ketamine’s sustained antidepressant-like effects in mouse tests, while administered (2R,6R)-HNK produced antidepressant-like effects on its own. The claim accurately presents these as a preclinical suggestion, though the conversion experiment specifically tested sustained effects at 24 hours. (LLM, conf=0.92)
hedgeddirect- 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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“recent research demonstrating that ketamine significantly improved full remission rates for those presenting with severe acute suicidal ideation, though this effect differed based on primary diagnosis [76].”
§ Ketamine in neuropsychiatric disorders: an update > Suicidal ideation
What the sources say
- Supportedcites [76] Abbar M, Demattei C, El-Hage W, Llorca P-M, Samalin L, Demaricourt P, et al. Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. BMJ. 2022;376:e067194. source
The Results report significantly higher full remission of suicidal ideas at day 3 with ketamine than placebo (63.0% versus 31.6%; P<0.001). They also report a significant interaction with diagnosis (P=0.02); the Discussion’s Principal findings describe a strong effect in bipolar disorder but non-significant effects in the other diagnostic groups. (LLM, conf=0.94)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Multiple meta-analyses and systematic reviews have demonstrated that ketamine significantly reduces suicidal ideation within one day and up to six weeks, an effect that appears to be at least partially independent of its effects on mood [72][73][74][75].”
§ Ketamine in neuropsychiatric disorders: an update > Suicidal ideation
What the sources say
- Partly supportedcites [72] Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry. 2018;175:150–58. sourceExperimental — accuracy not yet measured
The Abstract Conclusions report reduced suicidal thoughts within one day and for up to one week, with effects partially independent of mood effects. They do not support the claimed duration of up to six weeks; the Discussion says effects beyond one week had not been thoroughly investigated. Page numbers are not provided in our copy. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [73] Hochschild A, Grunebaum MF, Mann JJ. The rapid anti-suicidal ideation effect of ketamine: a systematic review. Prev Med. 2021;152:106524. source
- Partly supportedcites [74] Witt K, Potts J, Hubers A, Grunebaum MF, Murrough JW, Loo C, et al. Ketamine for suicidal ideation in adults with psychiatric disorders: a systematic review and meta-analysis of treatment trials. Aust N Z J Psychiatry. 2020;54:29–45. sourceExperimental — accuracy not yet measured
The Results (p. 13) report a significant reduction in suicidal ideation within one day and through 72 hours, but no significant effect after 72 hours; the claimed benefit up to six weeks is not supported. The Discussion (p. 15) says the effects on suicidality and depression may not be completely correlated, supporting the cautious suggestion of partial independence. (LLM, conf=0.88)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“One double-blind, crossover trial (n = 37) found that 69% of participants had complete remission of suicidal ideation after six ketamine infusions, an effect maintained with weekly maintenance infusions [83].”
§ Ketamine in neuropsychiatric disorders: an update > Suicidal ideation
What the sources say
- Partly supportedcites [83] Phillips JL, Norris S, Talbot J, Hatchard T, Ortiz A, Birmingham M, et al. Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression. Neuropsychopharmacology. 2020;45:606–12. sourceExperimental — accuracy not yet measured
The Abstract and ‘Maintenance ketamine infusions’ section report 37 participants and that 24 participants (69%) had no suicidal ideation after six repeated infusions. However, the double-blind crossover applied only to the initial single-infusion phase; the six-infusion and weekly maintenance phases were open-label. The Discussion says weekly infusions sustained reductions in suicidal ideation among responders, not that the 69% complete-alleviation rate was maintained. (LLM, conf=0.88)
plaindirectn = 37- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, it should be noted that a recent systematic review found that intranasal esketamine did not perform better than placebo at reducing suicidal ideation [90], though this finding may have been confounded by the high placebo response rate that exists when assessing suicidal ideation [91].”
§ Ketamine in neuropsychiatric disorders: an update > Suicidal ideation
What the sources say
- Supportedcites [90] Jollant F, Colle R, Nguyen TML, Corruble E, Gardier AM, Walter M, et al. Ketamine and esketamine in suicidal thoughts and behaviors: a systematic review. Ther Adv Psychopharmacol. 2023;13:20451253231151327. source
The Results report that three trials of intranasal esketamine versus placebo found no significant reduction in suicidal ideation relative to the control arm. The Conclusion likewise states that intranasal esketamine did not differ from placebo. The high-placebo-response explanation is attached to a different citation [91], so it is not part of the claim assessed against this source. (LLM, conf=0.94)
- Partly supportedcites [91] Bloomfield-Clagett B, Ballard ED, Greenstein DK, Wilkinson ST, Grunebaum MF, Murrough JW, et al. A participant-level integrative data analysis of differential placebo response for suicidal ideation and nonsuicidal depressive symptoms in clinical trials of intravenous racemic ketamine. Int J Neuropsychopharmacol. 2022;25:827–38. sourceExperimental — accuracy not yet measured
Citation [91] supports the placebo-response caveat, not the preceding systematic-review finding attributed to [90]. The Discussion reports preliminary evidence of a greater placebo response for suicidal ideation and suggests this may contribute to modest findings in IV ketamine trials. The paper says intranasal esketamine was not the subject of its analysis, so it does not establish that placebo response confounded the esketamine finding. (LLM, conf=0.84)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Only two pharmacotherapies are currently approved for PTSD-sertraline and paroxetine-and both have high relapse rates [100]”
§ Ketamine in neuropsychiatric disorders: an update > Anxiety-related disorders
What the sources say
- Partly supportedcites [100] Hoskins M, Pearce J, Bethell A, Dankova L, Barbui C, Tol WA, et al. Pharmacotherapy for post-traumatic stress disorder: systematic review and meta-analysis. Br J Psychiatry. 2015;206:93–100. sourceExperimental — accuracy not yet measured
The discussion of individual drugs (section labelled SKB627 E; page unavailable) treats sertraline and paroxetine as pharmacotherapies for PTSD. The paper does not establish that they are the only approved drugs or report high relapse rates for both; its stated outcome measures are symptom severity and early withdrawal. (LLM, conf=0.75)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Minimal clinical research supports these findings, suggesting that risks of dependency are extremely low when ketamine is administered in a medical setting [158-160]”
§ Ketamine in neuropsychiatric disorders: an update > Substance and alcohol misuse
What the sources say
- Partly supportedcites [158] Acevedo-Diaz EE, Cavanaugh GW, Greenstein D, Kraus C, Kadriu B, Zarate CAJ, et al. Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression. J Affect Disord. 2020;263:568–75. sourceExperimental — accuracy not yet measured
The Results (Cravings/Addiction behaviors; page unavailable) report no observed cravings or addiction behavior during inpatient follow-up of up to three months after a single ketamine infusion. But the Discussion (Strengths and limitations; page unavailable) says dependence was not formally measured and the findings do not cover repeated dosing or other routes. The paper therefore does not establish that dependency risk is “extremely low” across medical settings. (LLM, conf=0.88)
- Supportedcites [159] Feifel D, Dadiomov D, Lee KC. Safety of repeated administration of parenteral ketamine for depression. Pharmaceuticals. 2020;13:151. source
The Discussion reports no identified cases of addiction attributable to parenteral ketamine for depression in the authors’ survey or literature review, and suggests that monitored administration may help explain this finding. The Introduction notes that evidence on long-term outcomes remains limited. The finding concerns supervised parenteral treatment for depression, rather than every form of ketamine administered medically. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [160] Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, et al. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015;76:247–52. source
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Although it does not act as rapidly as ketamine, Auvelity demonstrated a significant difference from placebo at one week and up until six weeks (n = 327) [186]”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
What the sources say
- Partly supportedcites [186] Iosifescu DV, Jones M, O’Gorman C, Streicher C, Feliz S, Fava M, et al. Efficacy and safety of AXS-05 (dextromethorphan-bupropion) in patients with major depressive disorder: A phase 3 randomized clinical trial (GEMINI). J Clin Psychiatry. 2022;83:21m14345. sourceExperimental — accuracy not yet measured
The Discussion reports significantly greater reductions in MADRS scores with AXS-05 than with placebo starting at week 1 and continuing through week 6. Patient Characteristics reports 327 participants randomized, although the efficacy analysis included 318. The paper does not compare how rapidly AXS-05 and ketamine act, so that part of the sentence is unsupported by this source. (LLM, conf=0.88)
boosteddirectn = 327- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Metabotropic glutamate receptors (mGluRs) have repeatedly been implicated in the pathophysiology of depression, and mGluRs2/3 are known to mediate levels of glutamate and synaptic plasticity [189]”
§ Ketamine in neuropsychiatric disorders: an update > mGluR2/3 antagonists
What the sources say
- Partly supportedcites [189] Machado-Vieira R, Manji HK, Zarate CA. The role of the tripartite glutamatergic synapse in the pathophysiology and therapeutics of mood disorders. Neuroscientist. 2009;15:525–39. sourceExperimental — accuracy not yet measured
Section II.E links mGluRs to depression through animal-model findings, but says data linking mGluR dysfunction to mood disorders are sparse; this qualifies the claim that they have repeatedly been implicated. The Introduction says metabotropic receptors modulate synaptic plasticity, but our copy does not establish specifically that mGluR2/3 mediate glutamate levels and synaptic plasticity. Page numbers were not available in the indexed passages. (LLM, conf=0.86)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“placebo response rates are high in depression and suicidality research, as well in trials with rapid-acting antidepressants [104]”
§ Ketamine in neuropsychiatric disorders: an update > Pitfalls in current research
What the sources say
- Partly supportedcites [104] Abdallah CG, Roache JD, Gueorguieva R, Averill LA, Young-McCaughan S, Shiroma PR, et al. Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial. Neuropsychopharmacology. 2022;47:1574–81. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports an unexpectedly large placebo effect in this ketamine trial and says high placebo response is not uncommon in the field. The trial studied PTSD symptoms in veterans and active-duty military personnel; these passages do not establish high placebo response rates specifically in depression or suicidality research, or across rapid-acting antidepressant trials generally. (LLM, conf=0.86)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Auvelity is hypothesized to work via the NMDAR antagonism of dextromethorphan, which is prolonged by bupropion, a norepinephrine-dopamine reuptake inhibitor [187]”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
What the sources say
- Supportedcites [187] Stahl SM. Dextromethorphan/bupropion: a novel oral NMDA (N-methyl-d-aspartate) receptor antagonist with multimodal activity. CNS Spectr. 2019;24:461–66. source
The Introduction identifies dextromethorphan as an NMDA receptor antagonist and bupropion as a norepinephrine-dopamine reuptake inhibitor. It also explains that bupropion inhibits CYP2D6, increasing dextromethorphan exposure; Figure 1 describes this as inhibiting its metabolism and maintaining therapeutic concentrations. (LLM, conf=0.93)
hedgedconditional- 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“and in a small cohort (n = 3) of participants with PTSD [178]”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
What the sources say
- Partly supportedcites [178] Varias A, van Roessel P, Parsiani M, Filippou-Frye M, Neylan TC, Nagele P, et al. Does nitrous oxide help veterans with post-traumatic stress disorder (PTSD)? A case series. J Clin Psychiatry. 2020;81:20I13393. sourceExperimental — accuracy not yet measured
The Method section describes three participants with PTSD inhaling 50% nitrous oxide. The Results report rapid improvement in PTSD symptoms in two participants, but do not report antidepressant outcomes or a statistically significant effect; the authors also caution that this was an uncontrolled case series. Page numbers are unavailable in our copy. (LLM, conf=0.88)
plaindirectn = 3- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Preclinically, (R)-ketamine does not induce conditioned place preference, deficits in prepulse inhibition, or hyperlocomotion [155-157]”
§ Ketamine in neuropsychiatric disorders: an update > Substance and alcohol misuse
What the sources say
- Partly supportedcites [155] Bonaventura J, Lam S, Carlton M, Boehm MA, Gomez JL, Solis O, et al. Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability. Mol Psychiatry. 2021;26:6704–22. sourceExperimental — accuracy not yet measured
The Results section reports no conditioned place preference with (R)-ketamine in male mice. It does not report a prepulse-inhibition test. Contrary to the hyperlocomotion claim, the Results state that 20 mg/kg (R)-ketamine increased locomotor activity; the finding absent for (R)-ketamine was locomotor sensitization over days (page not specified in our copy). (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [156] Chang LC, Zhang K, Pu Y, Qu Y, Wang S-M, Xiong Z, et al. Comparison of antidepressant and side effects in mice after intranasal administration of (R,S)-ketamine, (R)-ketamine, and (S)-ketamine. Pharm Biochem Behav. 2019;181:53–59. source
- Supportedcites [157] Yang C, Shirayama Y, Zhang JC, Ren Q, Yao W, Ma M, et al. R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Transl Psychiatry. 2015;5:e632. source
The Results section (“Behavioral side effects of R-ketamine and S-ketamine”) reports that R-ketamine had no effect on locomotion or prepulse inhibition in mice at the tested doses. It also reports no effect on conditioned place preference scores, supporting all three parts of the preclinical claim. (LLM, conf=0.94)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“More recent research is investigating adjunctive D-cycloserine for indications such as OCD, PTSD, and MDD [172-174]”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
What the sources say
- Supportedcites [172] Cole J, Sohn MN, Harris AD, Bray SL, Patten SB, McGirr A. Efficacy of adjunctive D-cycloserine to intermittent theta-burst stimulation for major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2022;79:1153–61. source
The Introduction states that the authors tested adjunctive D-cycloserine to improve intermittent theta-burst stimulation outcomes in MDD. This source supports the MDD example in the multi-citation sentence; it need not establish the OCD or PTSD examples. (LLM, conf=0.94)
- Partly supportedcites [173] Farrell LJ, Waters AM, Tiralongo E, Mathieu S, McKenzie M, Garbharran V, et al. Efficacy of D-cycloserine augmented brief intensive cognitive-behavioural therapy for paediatric obsessive-compulsive disorder: a randomised clinical trial. Depress Anxiety. 2022;39:461–73. sourceExperimental — accuracy not yet measured
The Discussion describes this paper as a randomized trial of D-cycloserine–augmented CBT for pediatric OCD, supporting the OCD example. The References list a review covering PTSD, but this paper does not investigate PTSD, and no passage found addresses D-cycloserine for MDD. Pages are not specified in our copy. (LLM, conf=0.88)
- Supportedcites [174] Inslicht SS, Niles AN, Metzler TJ, Lipshitz SAL, Otte C, Milad MR, et al. Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD. Neuropsychopharmacology. 2022;47:1945–52. source
The Discussion reports clinical trials investigating D-cycloserine in PTSD patients, including its use with exposure treatment. In this multi-citation sentence, the source supports the PTSD example; it is not being relied on for the OCD or MDD examples. (LLM, conf=0.91)
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.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Auvelity has also received a fast-track designation from the FDA to treat Alzheimer's disease”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
What the sources say
- Could not verifycites [188] Lepkowsky CM. Auvelity as a potential treatment for Alzheimer’s disease. Med Res Arch. 2022;10. https://doi.org/10.18103/mra.v10i10.3206. sourceExperimental — accuracy not yet measured
The 'Auvelity: A Novel Antidepressant' section reports FDA approval for major depressive disorder, while the Discussion and Conclusion describes treatment of Alzheimer’s disease as hypothetical. Neither section reports an FDA fast-track designation for Alzheimer’s disease; the absence of approval for that indication does not settle whether a fast-track designation was granted. Searches for 'fast-track designation' and 'fast track FDA designation' found no passage addressing it. (LLM, conf=0.75)
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.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Broadly, these agents demonstrated no significant antidepressant efficacy and an adverse events profile that led to the early terminations of some clinical trials in indications such as MDD, TRD, and Parkinson's disease [169,170]”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
What the sources say
- Partly supportedcites [169] Nutt JG, Gunzler SA, Kirchhoff T, Hogarth P, Weaver JL, Krams M, et al. Effects of a NR2B selective NMDA glutamate antagonist, CP‐101,606, on dyskinesia and parkinsonism. Mov Disord. 2008;23:1860–66. sourceExperimental — accuracy not yet measured
The Results (Adverse Events; page unavailable) report abnormal thinking, depersonalization, and amnesia in patients with Parkinson’s disease receiving CP-101,606. The paper does not report antidepressant efficacy in MDD or TRD, or say that adverse events led to early termination of a trial. (LLM, conf=0.84)
- Partly supportedcites [170] Kadriu B, Musazzi L, Henter ID, Graves M, Popoli M, Zarate CA Jr. Glutamatergic neurotransmission: pathway to developing novel rapid-acting antidepressant treatments. Int J Neuropsychopharmacol. 2019;22:119–35. sourceExperimental — accuracy not yet measured
The MK-0657 (CERC-301) and JNJ40411813/ADX71149 sections report trials without significant antidepressant efficacy. The CP-101,606/Traxoprodil section reports adverse effects and discontinuation of that compound’s development, but it also reports significant antidepressant effects; it does not say a clinical trial ended early. The passages do not substantiate early trial terminations across MDD, TRD, and Parkinson’s disease. (LLM, conf=0.85)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“These findings were not replicated with other NMDAR antagonists or with 6,6-d2-(R,S)-ketamine [193]”
§ Ketamine in neuropsychiatric disorders: an update > mGluR2/3 antagonists
What the sources say
- Supportedcites [193] Zanos P, Highland JN, Stewart BW, Georgiou P, Jenne CE, Lovett J, et al. (2R,6R)-hydroxynorketamine exerts mGlu2 receptor-dependent antidepressant actions. Proc Natl Acad Sci USA. 2019;116:6441–50. source
The Results report that three other NMDAR antagonists did not prevent mGlu2/3 receptor agonist-induced hyperthermia. They also report that 6,6-dideuteroketamine did not prevent it, in contrast to ketamine. The claim is supported for this specific finding. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Co-administration of ketamine and an mGluR2/3 antagonist also sustained antidepressant-like responses in another animal model [197], which further supports mGluR2/3 antagonists as effective adjunctive therapies.”
§ Ketamine in neuropsychiatric disorders: an update > mGluR2/3 antagonists
What the sources say
- Supportedcites [197] Rafało-Ulińska A, Brański P, Pałucha-Poniewiera A. Combined administration of (R)-ketamine and the mGlu2/3 receptor antagonist LY341495 induces rapid and sustained effects in the CUMS model of depression via a TrkB/BDNF-dependent mechanism. Pharmaceuticals. 2022;15:125. source
The Results (§2.4; page unavailable) report anti-apathetic and anti-anhedonic effects three days after (R)-ketamine and LY341495 were coadministered in the mouse CUMS model. The Discussion (§3; page unavailable) describes the combination as a potential treatment for experimental trials, consistent with the citing authors’ adjunctive-therapy interpretation. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“RO4995819 (decoglurant), an mGluR2/3 NAM, has also completed Phase 1 clinical trials and a Phase 2 trial in partially refractory MDD, but no significant differences were observed between decoglurant and placebo [195]”
§ Ketamine in neuropsychiatric disorders: an update > mGluR2/3 antagonists
What the sources say
- Supportedcites [195] Umbricht D, Niggli M, Sanwald-Ducray P, Deptula D, Moore R, Grünbauer W, et al. Randomized, double-blind, placebo-controlled trial of the mGlu2/3 negative allosteric modulator decoglurant in partially refractory major depressive disorder. J Clin Psychiatry. 2020;81:18m12470. source
The Abstract (page not available) identifies decoglurant as an mGlu2/3 negative allosteric modulator, describes earlier safety studies in healthy volunteers, and identifies the current study as a phase 2 trial in partially refractory MDD. It reports no significant differences between decoglurant and placebo on the primary depression outcome. The earlier studies are not explicitly labeled phase 1 in our copy, but the description is consistent with the citing sentence. (LLM, conf=0.88)
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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It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“While AMPAR PAMs appeared to be well-tolerated in earlyphase clinical trials, failures to improve cognition and mood have consistently been observed [201,202]”
§ Ketamine in neuropsychiatric disorders: an update > AMPAR modulators
What the sources say
- Not checked — no full text of the sourcecites [201] Chappell AS, Gonzales C, Williams J, Witte MM, Mohs RC, Sperling R. AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Neurology. 2007;68:1008–12. source
- Partly supportedcites [202] Trzepacz PT, Cummings J, Konechnik T, Forrester TD, Chang C, Dennehy EB, et al. Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer’s disease. Int Psychogeriatr. 2013;25:707–19. sourceExperimental — accuracy not yet measured
The Results (Safety evaluation; page not provided) say mibampator was well tolerated. The Results (Efficacy; page not provided) report no treatment-group advantage on the cognitive measure or depression scale, although apathy improved significantly with mibampator. This trial of one AMPA receptor potentiator does not establish that failures to improve cognition and mood were consistently observed across AMPAR PAMs. (LLM, conf=0.86)
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Another restingstate fMRI study found that ketamine increased frontostriatal connectivity in participants with TRD, an effect that was disrupted when ketamine was administered to healthy volunteers [9]”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
What the sources say
- Supportedcites [9] Mkrtchian A, Evans JW, Kraus C, Yuan P, Kadriu B, Nugent AC, et al. Ketamine modulates fronto-striatal circuitry in depressed and healthy individuals. Mol Psychiatry. 2021;26:3292–301. source
The Results (Fig. 1) report increased fronto-striatal functional connectivity after ketamine in participants with TRD and reduced connectivity in healthy volunteers, measured by resting-state fMRI. The Discussion describes this as normalization in TRD participants but disruption in healthy volunteers. (LLM, conf=0.94)
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.
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It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“PET imaging studies found that increased 5-HT 1B receptor binding was associated with ketamine response in participants with TRD and correlated with depression symptom ratings at baseline [207]”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
What the sources say
- Partly supportedcites [207] Tiger M, Veldman ER, Ekman C-J, Halldin C, Svenningsson P, Lundberg J. A randomized placebo-controlled PET study of ketamine´ s effect on serotonin1B receptor binding in patients with SSRI-resistant depression. Transl Psychiatry. 2020;10:159. sourceExperimental — accuracy not yet measured
The Discussion reports that baseline ventral-striatal 5-HT1B receptor binding correlated with both ketamine-related symptom change and pretreatment depression ratings. But it says larger treatment effects occurred in patients with lower—not increased—pretreatment binding. The reported increase in hippocampal binding after ketamine was a separate finding, not an association with response. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“another study found similar baseline differences between healthy volunteers and individuals with MDD but did not replicate differences in global brain connectivity after ketamine versus placebo [210]”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
What the sources say
- Supportedcites [210] Kraus C, Mkrtchian A, Kadriu B, Nugent AC, Zarate CA Jr, Evans JW. Evaluating global brain connectivity as an imaging marker for depression: influence of preprocessing strategies and placebo-controlled ketamine treatment. Neuropsychopharmacology. 2020;45:982–89. source
The Discussion reports baseline global brain connectivity differences between participants with MDD and healthy controls, while noting that these differences were detected only with global signal regression. It also states that the study found no ketamine-versus-placebo effect on global brain connectivity. The scans were obtained 48–72 hours after infusion. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“TS-161, an mGluR2/3 antagonist, completed a Phase 1 evaluation of its safety profile, tolerability, and pharmacokinetics and was found to be safe and well-tolerated with high rates of conversion to its active metabolite and sufficient CSF penetration for pharmacological effects [194]”
§ Ketamine in neuropsychiatric disorders: an update > mGluR2/3 antagonists
What the sources say
- Supportedcites [194] Watanabe M, Marcy B, Hiroki A, Watase H, Kinoshita K, Iijima M, et al. Evaluation of the safety, tolerability, and pharmacokinetic profiles of TP0473292 (TS-161), a prodrug of a novel orthosteric mGlu2/3 receptor antagonist TP0178894, in healthy subjects and its antidepressant-like effects in rodents. Neuropsychopharmacology. 2022;25:106–17. source
The Abstract (Methods) identifies a first-in-human Phase 1 study in healthy subjects. The Abstract (Conclusions) reports that TS-161 was safe and well tolerated, was extensively converted to its active metabolite, and achieved CSF penetration predicted to be sufficient for pharmacological effects. The Discussion specifies that tolerability was established within the tested dose ranges. (LLM, conf=0.94)
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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It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“this pattern mirrored measurements from healthy volunteers after a placebo infusion [212], suggesting that ketamine normalized function.”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
What the sources say
- Supportedcites [212] Reed JL, Nugent AC, Furey ML, Szczepanik JE, Evans JW, Zarate CA Jr. Effects of ketamine on brain activity during emotional processing: diferential findings in depressed versus healthy control participants. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019;4:610–18. source
The Discussion states that brain activity in participants with major depressive disorder after ketamine became more similar to that in healthy controls after placebo, suggesting that ketamine may normalize BOLD activation. The claim preserves that interpretation. (LLM, conf=0.94)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“an mGluR2/3 agonistinduced hypothermic assay demonstrated that racemic ketamine and (2R,6R)-HNK prevented the increases in body temperature induced by an mGluR2/3 orthostatic agonist (LY379628), implicating mGluR2/3 antagonism in ketamine's antidepressant effects [193]”
§ Ketamine in neuropsychiatric disorders: an update > mGluR2/3 antagonists
What the sources say
- Partly supportedcites [193] Zanos P, Highland JN, Stewart BW, Georgiou P, Jenne CE, Lovett J, et al. (2R,6R)-hydroxynorketamine exerts mGlu2 receptor-dependent antidepressant actions. Proc Natl Acad Sci USA. 2019;116:6441–50. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A key area of interest for elucidating ketamine's underlying mechanisms of action has been measuring changes in gamma oscillations, as they are closely regulated by GABA A modulation and AMPAR-mediated depolarization, making them a valuable measure of excitatory/inhibitory balance [204]”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
What the sources say
- Partly supportedcites [204] Gandal MJ, Sisti J, Klook K, Ortinski PI, Leitman V, Liang Y, et al. GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction. Transl Psychiatry. 2012;2:e142. sourceExperimental — accuracy not yet measured
The Introduction and Results (‘Reduced gamma signal-to-noise ratio’; page unavailable) link gamma activity to excitatory–inhibitory balance and describe gamma abnormalities as a potential biomarker. The Discussion (‘Baclofen mechanism of action’; page unavailable) links GABA release and GABAA-mediated spike timing to gamma synchrony. Our copy does not establish the claimed role of AMPAR-mediated depolarization. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
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
“few studies have yet examined drug-drug interactions between ketamine and monoaminergic-based therapeutics.”
§ Ketamine in neuropsychiatric disorders: an update > FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no 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
“many of the involved neurobiological mechanisms remain unclear”
§ Ketamine in neuropsychiatric disorders: an update > FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist with rapid-acting therapeutic effects, has created a paradigm shift in the field of neuropsychopharmacology.”
§ Ketamine in neuropsychiatric disorders: an update > INTRODUCTION
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“As a phencyclidine derivative, ketamine is a highly water-and lipid-soluble agent that can rapidly cross the blood-brain barrier [15].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Not checked — no full text of the sourcecites [15] Herd DW, Anderson BJ, Keene NA, Holford NH. Investigating the pharmacodynamics of ketamine in children. Paediatr Anaesth. 2008;18:36–42. 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.
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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
“Based on significant clinical evidence, the Food and Drug Administration (FDA) approved the use of intranasal esketamine (Spravato TM )-the (S+) enantiomer of ketamine-for adults with TRD in 2019; in 2020, it was approved to treat adults with major depression and acute suicidal ideation or behavior.”
§ Ketamine in neuropsychiatric disorders: an update > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
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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
“Although subanesthetic-dose ketamine was first studied for its antidepressant effects, its varied pharmacological actions suggested that it could also be effective in other neuropsychiatric disorders.”
§ Ketamine in neuropsychiatric disorders: an update > INTRODUCTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- 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.
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 addition to its known clinical side effects-including sedation, dizziness, dissociation, and psychotomimetic symptoms -ketamine also has a relatively long history of recreational substance misuse.”
§ Ketamine in neuropsychiatric disorders: an update > INTRODUCTION
boosted- 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
“Like phencyclidine, ketamine binds to a site located deep within the NMDAR channel, necessitating the removal of the magnesium block before binding [16].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Not checked — no full text of the sourcecites [16] MacDonald JF, Miljkovic Z, Pennefather P. Use-dependent block of excitatory amino acid currents in cultured neurons by ketamine. J Neurophysiol. 1987;58:251–66. 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.
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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
“Although a direct comparison between racemic ketamine and (R)-ketamine has yet to be conducted”
§ Ketamine in neuropsychiatric disorders: an update > Depression and bipolar disorder
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.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The elimination rate of ketamine is nearly equal to that of liver blood flow, with a half-life of approximately two to three hours [20,21].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Not checked — no full text of the sourcecites [20] Domino EF, Domino SE, Smith RE, Domino LE, Goulet JR, Domino KE, et al. Ketamine kinetics in unmedicated and diazepam-premedicated subjects. Clin Pharm Ther. 1984;36:645–53. source
- Not checked — no full text of the sourcecites [21] Schüttler J, Stanski DR, White PF, Trevor A, Horai Y, Verotta D, et al. Pharmacodynamic modeling of the EEG effects of ketamine and its enantiomers in man. J Pharmacokinet Biopharm. 1987;15:241–53. 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
“Another study found that ketamine significantly decreased depressive symptoms in 53 older adults, with a 27% remission rate after four infusions, but was associated with transient increases in hypertension [60].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not checked — no full text of the sourcecites [60] Lipsitz O, Di Vincenzo JD, Rodrigues NB, Cha DS, Lee Y, Greenberg D, et al. Safety, tolerability, and real-world effectiveness of intravenous ketamine in older adults with treatment-resistant depression: a case series. Am J Geriatr Psychiatry. 2021;29:899–913. source
plaindirectn = 53- 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
“Notable differences in metabolism exist between the two enantiomers: (S)-ketamine has a higher demethylation and clearance rate, as well as a wider distribution pattern than either (R)-ketamine or racemic (R,S)-ketamine [22].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Not checked — no full text of the sourcecites [22] Geisslinger G, Menzel-Soglowek S, Kamp HD, Brune K. Stereoselective high-performance liquid chromatographic determination of the enantiomers of ketamine and norketamine in plasma. J Chromatogr. 1991;568:165–76. 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.
In the paper
“Another recent, small, controlled trial (n = 10) obtained similar results [44], suggesting that larger clinical trials are needed to elucidate (R)-ketamine's antidepressant potential.”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not checked — no full text of the sourcecites [44] Leal GC, Souza-Marques B, Mello RP, Bandeira ID, Caliman-Fontes AT, Carneiro BA, et al. Arketamine as adjunctive therapy for treatment-resistant depression: a placebo-controlled pilot study. J Affect Disord. 2023;330:7–15. source
hedgedn = 10- 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
“Subsequent metabolism of norketamine to dehydronorketamine (DHNK) and hydroxynorketamine (HNK) also occurs rapidly, potentially contributing to its therapeutic effects (described below).”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
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 addition, no decreases in therapeutic efficacy were observed with repeated doses, suggesting that chronic ketamine administration could be useful in maintaining antidepressant effects.”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not checked — no full text of the sourcecites [59] Alnefeesi Y, Chen-Li D, Krane E, Jawad MY, Rodgrigues NB, Ceban F, et al. Real-world effectiveness of ketamine in treatment-resistant depression: a systematic review & meta-analysis. J Psychiatr Res. 2022;151:693–709. 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.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“This suggests that low-dose concentrations of ketamine may reduce complications in patients also receiving ECT, though mixed results from meta-analyses of anesthetic-dose ketamine suggest that cautious interpretation is warranted [49,52,53].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not checked — no full text of the sourcecites [49] Zheng W, Li X-H, Zhu X-M, Cai D-B, Yang X-H, Ungvari GS, et al. Adjunctive ketamine and electroconvulsive therapy for major depressive disorder: a meta-analysis of randomized controlled trials. J Affect Disord. 2019;250:123–31. source
- Not checked — no full text of the sourcecites [52] Li D-J, Wang F-C, Chu C-S, Chen T-Y, Tang C-H, Yang W-C, et al. Significant treatment effect of add-on ketamine anesthesia in electroconvulsive therapy in depressive patients: a meta-analysis. Eur Neuropsychopharmacol. 2017;27:29–41. source
- Not checked — no full text of the sourcecites [53] McGirr A, Berlim MT, Bond DJ, Neufeld NH, Chan PY, Yatham LN, et al. A systematic review and meta-analysis of randomized controlled trials of adjunctive ketamine in electroconvulsive therapy: efficacy and tolerability. J Psychiatr Res. 2015;62:23–30. 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.
In the paper
“Clinically, an initial open-label pilot trial found that (R)-ketamine exerted significant antidepressant effects in seven individuals with TRD and, furthermore, was associated with few dissociative symptoms [42].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not checked — no full text of the sourcecites [42] Leal GC, Bandeira ID, Correia-Melo FS, Telles M, Mello RP, Vieira F, et al. Intravenous arketamine for treatment-resistant depression: open-label pilot study. Eur Arch Psychiatr Clin Neurosci. 2021;271:577–82. source
plaindirectn = 7- 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
“However, the necessity of NMDAR inhibition for ketamine's antidepressant effects remains unknown.”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
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
“Another study comparing intranasal esketamine with intravenous racemic ketamine (n = 62) also found no significant differences in rates of response and remission, though the number of treatments needed to achieve remission was significantly higher for intranasal esketamine [38].”
§ Ketamine in neuropsychiatric disorders: an update > Depression and bipolar disorder
What the sources say
- Not checked — no full text of the sourcecites [38] Singh B, Kung S, Pazdernik V, Schak KM, Geske J, Schulte PJ, et al. Comparative effectiveness of intravenous ketamine and intranasal esketamine in clinical practice among patients with treatment-refractory depression: an observational study. J Clin Psychiatry. 2023;84:22m14548. source
plainn = 62- 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
“Interestingly, one study found that adjunctive ketamine performed worse on measures of suicidality than ketamine monotherapy, though no differences were observed on other measures of depression, anxiety, or functional impairment (n = 220) [54].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not checked — no full text of the sourcecites [54] Di Vincenzo JD, Lipsitz O, Rodrigues NB, Lee Y, Gill H, Kratiuk K, et al. Ketamine monotherapy versus adjunctive ketamine in adults with treatment-resistant depression: results from the Canadian Rapid Treatment Centre of Excellence. J Psychiatr Res. 2021;143:209–14. source
plaindirectn = 220- 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 addition, steady-state concentrations of metabolites such as HNK are also impacted in a stereoselective manner, which could contribute to enantiomer-specific therapeutic effects [23].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Not checked — no full text of the sourcecites [23] Weiss M, Siegmund W. Pharmacokinetic modeling of ketamine enantiomers and their metabolites after administration of prolonged‐release ketamine with emphasis on 2, 6‐hydroxynorketamines. Clin Pharm Drug Dev. 2022;11:194–206. 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
“Another recent comparison of intravenous esketamine (0.25 mg/kg) (n = 34) and racemic ketamine (0.5 mg/kg) (n = 29) found no significant differences in remission rates or safety profile at 24 h after an acute infusion, though there was a slight trend towards decreased MADRS scores and increased response rates in those who received racemic ketamine at 72 h and seven days [37].”
§ Ketamine in neuropsychiatric disorders: an update > Depression and bipolar disorder
What the sources say
- Not checked — no full text of the sourcecites [37] Correia-Melo FS, Leal GC, Vieira F, Jesus-Nunes AP, Mello RP, Magnavita G, et al. Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study. J Affect Disord. 2020;264:527–34. source
plainn = 34- 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
“Multiple studies have now tested the effects of adjunctive ketamine on ECT outcomes and found that ketamine most effectively improves ECT outcomes when it is administered together with another anesthetic; no significant effects were found with ketamine administration alone [49].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not checked — no full text of the sourcecites [49] Zheng W, Li X-H, Zhu X-M, Cai D-B, Yang X-H, Ungvari GS, et al. Adjunctive ketamine and electroconvulsive therapy for major depressive disorder: a meta-analysis of randomized controlled trials. J Affect Disord. 2019;250:123–31. 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
“Ketamine also inhibits NMDAR-dependent bursting activity of lateral habenula neurons, reversing the increases in bursts and thetaband synchronization observed in depression [29].”
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
What the sources say
- Not checked — no full text of the sourcecites [29] Yang Y, Cui Y, Sang K, Dong Y, Ni Z, Ma S, et al. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature. 2018;554:317–22. 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
“the first large-scale, Phase 2a, proof-of-concept clinical trial (n = 102) (NCT05414422) found that (R)-ketamine (PCN-101) had no significant effect on baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores at 24 h postadministration, though it had a generally positive safety profile [43].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not matchedcites [43] Atai Life Sciences. atai Life Sciences announces results from Phase 2a trial of PCN-101 (R-ketamine) for treatment-resistant depression. 2023. https://www.globenewswire.com/news-release/2023/01/06/2584334/0/en/atai-Life-Sciences-Announces-Results-from-Phase-2a-Trial-of-PCN-101-R-ketamine-for-Treatment-Resistant-Depression.html.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainn = 102- 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.
- Not matched
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
“Ketamine has repeatedly been shown to effectively reduce the symptoms of major depressive disorder (MDD) and BD.”
§ Ketamine in neuropsychiatric disorders: an update > Depression and bipolar disorder
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
“A recent meta-analysis [59] found that ketamine had substantial real-world effectiveness, with a mean response rate of 55.3% and a remission rate of 28.9%, but differences in remission rates varied across patient groups.”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not checked — no full text of the sourcecites [59] Alnefeesi Y, Chen-Li D, Krane E, Jawad MY, Rodgrigues NB, Ceban F, et al. Real-world effectiveness of ketamine in treatment-resistant depression: a systematic review & meta-analysis. J Psychiatr Res. 2022;151:693–709. 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
“Although a different study found that repeated ketamine infusions had no effect on severity of depressive symptoms or suicidal ideation, the 26 participants in that study had severe MDD with chronic suicidal ideation, suggesting that a higher ketamine dose or an increased number of infusions may have been necessary to see an effect [87].”
§ Ketamine in neuropsychiatric disorders: an update > Suicidal ideation
What the sources say
- Not checked — no full text of the sourcecites [87] Ionescu DF, Bentley KH, Eikermann M, Taylor N, Johnson-Akeju O, Swee MB, et al. Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: a randomized, double blind, placebo controlled trial. J Affect Disord. 2019;243:516–24. source
hedgedn = 26- 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
“However, a network meta-analysis found that ketamine was superior to other pharmacological treatments at two weeks after treatment initiation; at four, six, and eight weeks, quetiapine and risperidone augmentation were found to be the best and second best treatments, respectively [71].”
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
What the sources say
- Not checked — no full text of the sourcecites [71] Papadimitropoulou K, Vossen C, Karabis A, Donatti C, Kubitz N. Comparative efficacy and tolerability of pharmacological and somatic interventions in adult patients with treatment-resistant depression: a systematic review and network meta-analysis. Curr Med Res Opin. 2017;33:701–11. 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
“work in mice found no drug-induced sensitization or drug-evoked synaptic plasticity for ketamine, suggesting lower misuse liablity than the comparative substance, cocaine [68]”
§ Ketamine in neuropsychiatric disorders: an update > Substance and alcohol misuse
What the sources say
- Not checked — no full text of the sourcecites [68] Simmler LD, Li Y, Hadjas LC, Hiver A, van Zessen R, Lüscher C. Dual action of ketamine confines addiction liability. Nature. 2022;608:368–73. source
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
“a recent systematic review supported ketamine use for the treatment of OCD, though results appeared to vary across studies and require further investigation [117]”
§ Ketamine in neuropsychiatric disorders: an update > Anxiety-related disorders
What the sources say
- Not checked — no full text of the sourcecites [117] Bandeira ID, Lins-Silva DH, Cavenaghi VB, Dorea-Bandeira I, Faria-Guimarães D, Barouh JL, et al. Ketamine in the treatment of obsessive-compulsive disorder: a systematic review. Harv Rev Psychiatry. 2022;30:135–45. 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
“Strategies to mitigate placebo response include increasing study duration, randomizing the run-in period, and addressing functional blinding in rapid-acting antidepressant trials [162]”
§ Ketamine in neuropsychiatric disorders: an update > Pitfalls in current research
What the sources say
- Not checked — no full text of the sourcecites [162] Fava M, Evins AE, Dorer DJ, Schoenfeld DA. The problem of the placebo response in clinical trials for psychiatric disorders: culprits, possible remedies, and a novel study design approach. Psychother Psychosom. 2003;72:115–27. 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. It may state two separate claims as one.
In the paper
“baseline cerebral blood flow predicted MADRS reductions at 24 h postnitrous oxide administration, a finding not observed in control groups [179]”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
What the sources say
- Not checked — no full text of the sourcecites [179] Kim WSH, Dimick MK, Omrin D, Mitchell RHB, Riegart D, Levitt A, et al. Proof‐of‐concept randomized controlled trial of single‐session nitrous oxide for refractory bipolar depression: focus on cerebrovascular target engagement. Bipolar Disord. 2022;25:221–32. 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
“the recent development and/or repurposing of other neuropsychopharmacological interventions provides important insight into how different aspects of ketamine's unique pharmacology, such as NMDAR antagonism and AMPAR modulation, may contribute to symptom alleviation.”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM OTHER NOVEL THERAPEUTICS
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.
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
“Dextromethorphan is also a sigma-1 agonist, implicating a novel mechanism of action in rapid-acting antidepressant effects.”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
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
“This might be due to patients' expectations of benefits in clinical trials with novel substances, behavioral conditioning in research settings, or the striking overlap in neuroanatomical substrates between affected brain regions in MDD and placebo response [161]”
§ Ketamine in neuropsychiatric disorders: an update > Pitfalls in current research
What the sources say
- Not checked — no full text of the sourcecites [161] Enck P, Bingel U, Schedlowski M, Rief W. The placebo response in medicine: minimize, maximize or personalize? Nat Rev Drug Discov. 2013;12:191–204. 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.
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, despite early failures in the development of other NMDAR modulators as rapidacting antidepressants, several promising agents are currently under investigation.”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
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
“more data are currently available for ketamine/ esketamine than for other rapid-acting agents (e.g., serotonergic psychedelics)”
§ Ketamine in neuropsychiatric disorders: an update > Pitfalls in current research
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no 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 ketamine evidently has great clinical utility, its direct therapeutic mechanisms are still unclear.”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM OTHER NOVEL THERAPEUTICS
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: 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.
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 success of therapeutics with well-defined mechanisms of action can provide insight into how ketamine may target each neuropsychiatric disorder discussed above.”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM OTHER NOVEL THERAPEUTICS
plainconditional- 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: fails — The paper may give no 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. The paper may give no 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
“MIJ-821 is an NR2B negative allosteric modulator that binds to and inhibits the activity of NMDARs, thereby inhibiting abnormal neurotransmission.”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
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
“REL-1017 (esmethadone, d-methadone) is an NMDAR channel blocker that has demonstrated significant promise as a therapeutic.”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
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.
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
“Neuroimaging studies can provide a strong foundation to bridge preclinical and clinical research, allowing a non-invasive way to study changes in brain function.”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
boosteddirect- 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Techniques such as electroencephalography (EEG), magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), fMRI, and/or positron emission tomography (PET) allow for a macroscopic viewpoint of neurophysiological function.”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
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
“the study was conducted in healthy volunteers, and the results implicated a distinct time course for neural responses to ketamine that should be explored in future research [213].”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
What the sources say
- Not checked — no full text of the sourcecites [213] McMillan R, Forsyth A, Campbell D, Malpas G, Maxwell E, Dukart J, et al. Temporal dynamics of the pharmacological MRI response to subanaesthetic ketamine in healthy volunteers: a simultaneous EEG/fMRI study. J Psychopharmacol. 2019;33:219–29. source
hedgedcorrelational- 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.
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
“initial research has suggested that adverse events occur less freqently with maintenance treatments of intranasal esketamine”
§ Ketamine in neuropsychiatric disorders: an update > FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS
hedgedconditional- 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no 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
“variance in the dose used, the frequency of administration, and the duration of treatment can significantly impact results”
§ Ketamine in neuropsychiatric disorders: an update > FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS
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.
Probably not a substantial claim.
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 unique structure and function of AMPARs allow for multiple approaches to mediate glutamatergic activity and could still hold great promise for developing novel therapeutics.”
§ Ketamine in neuropsychiatric disorders: an update > AMPAR modulators
hedgedconditional- 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
“Deficits in global brain connectivity have also been repeatedly implicated in MDD and can be assessed using resting-state fMRI.”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
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
“This increased probability of glutamate release activates downstream mechanisms that activate mTORC1 signaling, leading to upregulation of synaptic density, PSD-95, and GluA1containing AMPAR surface insertion.”
§ Ketamine in neuropsychiatric disorders: an update > FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS
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
“a novel approach of combining EEG with fMRI suggested that increases in the subgenual anterior cingulate cortex after subanesthetic ketamine administration may be due to physiological noise; however, the study was conducted in healthy volunteers”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
hedgedconditional- 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
“ketamine has repeatedly been shown to increase AMPAR activity and throughput, suggesting that increasing AMPAR signaling itself may facilitate rapid-acting therapeutic effects.”
§ Ketamine in neuropsychiatric disorders: an update > AMPAR modulators
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.
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
“more potent NMDAR antagonism (associated with ketamine's dissociative and psychotomimetic effects) or other mechanisms may be necessary for rapid-acting antidepressant effects.”
§ Ketamine in neuropsychiatric disorders: an update > FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS
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.
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
“increasing evidence has suggested that ketamine is a promising treatment for BD, suicidal ideation, anxiety spectrum disorders, eating disorders, chronic pain, migraines, and substance use disorders.”
§ Ketamine in neuropsychiatric disorders: an update > FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS
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
“One of the hallmarks of most neuropsychiatric disorders is dysregulated neuroplasticity, which interrupts most facets of normal functioning, including normal cognitive, learning, and memory processes [203]”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
What the sources say
- Not checked — no full text of the sourcecites [203] Kays JL, Hurley RA, Taber KH. The dynamic brain: neuroplasticity and mental health. J Neuropsychiatry Clin Neurosci. 2012;24:118–24. 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.
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
“Preclinical PET imaging also provides a valuable tool for translating scientific results, allowing for high-throughput hypothesis testing before recruiting human participants.”
§ Ketamine in neuropsychiatric disorders: an update > INSIGHTS FROM NEUROIMAGING
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
“Other AMPAR PAMs, such as S18986, LY392098, and mibampator, which are thought to function by reducing desensitization of the ion channel [199]”
§ Ketamine in neuropsychiatric disorders: an update > AMPAR modulators
What the sources say
- Not checked — no full text of the sourcecites [199] Ornstein PL, Zimmerman DM, Arnold MB, Bleisch TJ, Cantrell B, Simon R, et al. Biarylpropylsulfonamides as novel, potent potentiators of 2-amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)-propanoic acid (AMPA) receptors. J Med Chem. 2000;43:4354–58. source
hedgedconditional- 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.
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 sideeffect profiles of ketamine and esketamine as prototypes for rapidacting substances are now well established”
§ Ketamine in neuropsychiatric disorders: an update > FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS
boosted- 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper relies on this without support.
Alcohol and substance misuse are highly prevalent, and current treatments have long-term relapse rates, so novel therapeutic approaches are needed.
“Alcohol and substance misuse are highly prevalent, and current treatments have long-term relapse rates, necessitating novel therapeutic approaches.”
The paper relies on this without support.
Substance use disorders are often resistant to traditional pharmacotherapy and behavioral interventions.
“Substance use disorders are often resistant to traditional pharmacotherapy and behavioral interventions.”
The paper relies on this without support.
Glutamatergic dysregulation is implicated across multiple substance use disorders.
“Glutamatergic dysregulation has been implicated across multiple substance use disorders, leading to interest in the putative therapeutic impact of ketamine.”
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
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
“However, two studies (n = 134 and n = 157, respectively) found that intermittent low-dose ketamine (0.3 mg/kg, administered before each ECT treatment) improved cognitive functioning and reduced psychiatric complications after ECT [50,51].”
§ Ketamine in neuropsychiatric disorders: an update > Depression and bipolar disorder
“Repeated/intermittent racemic ketamine (0.3 mg/kg) + ECT RCT (n = 157) No significant differences in remission rates, and greater cognitive impairment with ketamine-assisted ECT after ECT course was finished [51].”
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
§ Ketamine in neuropsychiatric disorders: an update > Eating disorders
“In an openlabel pilot study, repeated ketamine infusions were used in conjunction with a ketogenic diet in five individuals who had recovered from anorexia nervosa but still had persistent EDrelated thoughts and behaviors.Significant improvements were found across multiple measures on the Eating Disorder Examination Questionnaire and Clinical Impairment Assessment; importantly, these were found to last for up to six months [121].”
§ Ketamine in neuropsychiatric disorders: an update > FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS
“| Anorexia Nervosa | Repeated racemic ketamine (0.5 mg/kg), | Pilot study (n = 5) | Significant improvements in ED-related | | | intravenous + ketogenic diet | | thoughts and behaviors after 24 h [122]. |”
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
§ Ketamine in neuropsychiatric disorders: an update > Anxiety spectrum disorders
“Ketamine significantly reduced social anxiety up to two weeks after infusion [98].”
§ Ketamine in neuropsychiatric disorders: an update > Anxiety-related disorders
“ketamine effectively decreased ratings of anxiety within three hours, an effect that was maintained for up to two days postinfusion [98].”
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
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
“the FDA approved Auvelity (AXS-05), an extended-release oral tablet containing dextromethorphan and buprenorphine for the treatment of MDD in adults.”
§ Ketamine in neuropsychiatric disorders: an update > NMDAR modulators
“Auvelity is hypothesized to work via the NMDAR antagonism of dextromethorphan, which is prolonged by bupropion, a norepinephrine-dopamine reuptake inhibitor [187].”
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
§ Ketamine in neuropsychiatric disorders: an update > KETAMINE'S MECHANISM OF ACTION
“ketamine is also an opioid (mu, kappa, delta) and dopamine receptor agonist, inhibits monoamine reuptake, and antagonizes muscarinic receptors [32].”
§ Ketamine in neuropsychiatric disorders: an update > Substance and alcohol misuse
“its unique pharmacological profile that can reduce opioid withdrawal symptoms without direct mu-opioid receptor binding [150].”
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
§ Ketamine in neuropsychiatric disorders: an update > Racemic ketamine, varying dose and route of administration
“Repeated racemic ketamine (0.5 mg/kg), intravenous Retrospective analysis (n = 113)”
§ Ketamine in neuropsychiatric disorders: an update > Anxiety-related disorders
“One study found that repeat-dose ketamine rapidly improved anxiety, irritability, and agitation in 201 individuals with MDD or BD, and that participants with baseline anxiety, irritability, and agitation experienced a greater reduction in depressive symptoms and anxiety [94].”
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
§ Ketamine in neuropsychiatric disorders: an update > FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS
“| PTSD + chronic pain | Acute racemic ketamine (0.5 mg/kg), | RCT (n = 41) | Significant improvement of PTSD and |”
§ Ketamine in neuropsychiatric disorders: an update > Anxiety-related disorders
“one randomized, controlled trial (n = 40) found that ketamine successfully decreased symptoms of both chronic pain and PTSD, an effect that lasted seven days post-infusion [107].”
Citations
Cites
Items 201–223 of 223
Surjan, J., Grossi, J. D., Del Porto, J. A., Delfino, R. S., de Oliveira Cerqueira, R., Lucchese, A. C., Magalhães, E., Del Sant, L. C., Tuena, M. A., Nakahira, C., et al. (2022) · Clinical Drug Investigation · doi:10.1007/s40261-022-01193-z · Cited by 19
Extensive Underreported Exposure to Ketamine Among Electronic Dance Music Party Attendees
Palamar, J. J., Salomone, A., Rutherford, C. G., & Keyes, K. M. (2020) · Journal of General Internal Medicine · doi:10.1007/s11606-020-05672-x · Cited by 18
(Es)Ketamine for Suicidal Ideation and Behavior: Clinical Efficacy
Alario, A. A., & Niciu, M. J. (2022) · Chronic Stress · doi:10.1177/24705470221128017 · Cited by 17
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Subdissociative‐dose Ketamine Is Effective for Treating Acute Exacerbations of Chronic Pain
Lumanauw, D. D., Youn, S., Horeczko, T., Yadav, K., & Tanen, D. A. (2019) · Academic Emergency Medicine · doi:10.1111/acem.13755 · Cited by 14
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Intranasal Ketamine for Abortive Migraine Therapy in Pediatric Patients: A Single-Center Review
Turner, A. L., Shandley, S., Miller, E., Perry, M. S., & Ryals, B. (2020) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2019.10.007 · Cited by 11
Abdallah, C. G., Roache, J. D., Gueorguieva, R. V., et al. (2021) · medRxiv · doi:10.1101/2021.04.30.21256273 · Cited by 9
Ketamine Augmentation of Exposure Response Prevention Therapy for Obsessive Compulsive Disorder
Bottemanne, H., & Arnould, A. (2021) · Unpublished · doi:10.13140/rg.2.2.33281.48485 · Cited by 8
Bloomfield-Clagett, B., Ballard, E. D., Greenstein, D. K., Wilkinson, S. T., Grunebaum, M. F., Murrough, J. W., Mathew, S. J., Phillips, J. L., Fava, M., Sanacora, G., et al. (2022) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyac055 · Cited by 8
Self-citationShivanekar, S., Gopalan, P., Pizon, A., Spotts, C., Cruz, N., Lightfoot, M., Rohac, R., Baumeister, A., Griffo, A., Panny, B., et al. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph192113792 · Cited by 8
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Auvelity as a Potential Treatment for Alzheimer’s Disease
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Real-world study of intranasal ketamine for use in patients with refractory chronic migraine
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538. Cognitive Control Predicts Alleviation of OCD Symptoms by Ketamine
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Cited by
Sorted by citations
Nicosia, N., Giovenzana, M., Misztak, P., Mingardi, J., & Musazzi, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126521 · Cited by 135
“Other glutamatergic drugs still under preclinical/early clinical development include the following: R-ketamine, hydroxynorketamine, modulators of metabotropic receptors (especially mGluR2/3 antagonists), dextromethorphan, dextromethadone, and nitrous oxide [177,179–181].”
BackgroundMechanisms of SSRI Therapy and Discontinuation
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“9 10–15 Unlike traditional anti-depressants, which may take weeks to exert effects, ketamine can induce significant improvements in depression and suicidal ideation within hours of administration.”
Rodolico, A., Cutrufelli, P., Francesco, A. D., Aguglia, A., Catania, G., Concerto, C., Cuomo, A., Fagiolini, A. M., Lanza, G., Mineo, L., et al. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1325399 · Cited by 40
Li, M., Yang, X., Yang, J., Li, T., Cui, C., Peng, X., Lei, J., Ren, K., Ming, J., Zhang, P., et al. (2024) · Neuron · doi:10.1016/j.neuron.2024.06.026 · Cited by 34
Metadata
- Authors
- Johnston, J. N., Kadriu, B., Kraus, C., Henter, I. D., & Zarate, C. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Johnston, Jenessa N.
- Venue
- Neuropsychopharmacology
- Published
- 2023-06-20
- Volume
- 49
- Issue
- 1
- Pages
- 23-40
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC10700638
- OpenAlex
- W4381334012
- Cited by
- 108
- References
- 227
- Citations by year
- 2026: 28 · 2025: 41 · 2024: 36 · 2023: 3
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (ZIAMH002857)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- ketamine, esketamine, subanesthetic ketamine, rapid-acting antidepressants, depression, bipolar disorder, anxiety disorders, substance use disorders, eating disorders, chronic pain, hydroxynorketamine, enantiomers, suicidal ideation, anhedonia, mechanism of action, neuroimaging
- MeSH terms
- Antidepressive Agents, Anxiety Disorders, Bipolar Disorder, Depression, Humans, Ketamine, Anhedonia
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