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Cited by 37Treatment of Major DepressionElectroconvulsive Therapy StudiesAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Addictive potential of novel treatments for refractory depression and anxiety

Open access
Kolar, Dusan·2018·Neuropsychiatric Disease and Treatment
DOI 10.2147/ndt.s167538PMC PMC6003533
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Abstract

Treatment-resistant mood disorders and anxiety disorders require intensive treatment, but treatment options should balance benefits and adverse effects or other potential detrimental effects on patients, including the risk of developing prescription medication addiction. Some of the newer treatment modalities for mood and anxiety disorders may have similar properties to benzodiazepines. The goal of this review was to identify the potential for developing dependence on the novel treatment approaches to treatment-resistant depression and refractory anxiety disorders. PubMed, MEDLINE, PsycINFO, Ovid, Cochrane Library, and Google Scholar were searched. Ketamine is effective in improving symptoms of major depressive disorder, but with no sustained benefits. Long-term use of oral or intranasal ketamine formulations may be associated with the risk of developing dependence. Augmentation of stimulant medication is usually effective for residual symptoms of depression, but the effects are usually short lasting and there is a potential for abuse. Synthetic cannabinoids and medicinal cannabis are increasingly being prescribed for a number of medical conditions, including anxiety disorders, without enough evidence about their efficacy and with the risk of patients developing dependence. In summary, benzodiazepines, ketamine, stimulant medications, and cannabinoids have some common characteristics, including short-lasting benefits and the risk of developing prescription medication addiction with longer use. All of these treatments may raise ethical dilemmas about the appropriateness of prescribing these medications in the long run for patients with depression and anxiety disorders.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review examines the dependence risk of newer treatments for refractory depression and anxiety—ketamine, stimulant augmentation, and synthetic cannabinoids/medicinal cannabis—and argues they share short-lived benefits and potential for prescription medication addiction, similar to benzodiazepines. It concludes that clinicians should avoid long-term off-label use of these agents until more efficacy and safety evidence is available.

Key findings

  • Ketamine has rapid antidepressant effects within 2–4 h, but benefits are sustained for only 4–7 days; in one RCT of 47 patients with treatment-resistant depression, only 21 still met response criteria at day 7 after stopping infusions, and about 89% relapsed on average 19 days after receiving 6 infusions. Long-term oral or intranasal ketamine may increase dependence risk, but there is no available research on its addictive potential in depression treatment.
  • In an Australian open study of 50 patients with unipolar or bipolar depression, stimulant augmentation was very effective for melancholic symptoms in 20%, “somewhat effective” in 50% of each group, and ineffective in 30%; benefits were not sustained after discontinuation, and long-term use may lead to dependence, particularly on amphetamines. Stimulant augmentation is a third-line, level 3 evidence option in CANMAT guidelines.
  • Among 20 million Americans who used marijuana in 2013, up to 9% may become dependent, rising to 17% if use starts during adolescence; a systematic review and meta-analysis found no evidence for efficacy of cannabis and cannabinoid drugs in treating anxiety. A nabilone RCT for PTSD-associated nightmares had a small sample of only 10 patients, and there have been no studies on nabilone’s addictive potential.
  • Benzodiazepines, ketamine, stimulant medications, and cannabinoids share short-lasting benefits and risk of developing prescription medication addiction with longer use; ketamine is not recommended for treatment-resistant depression in any treatment guidelines, and CANMAT emphasizes its psychotomimetic side effects and abuse potential.

Methods

  • Narrative literature review searching PubMed, MEDLINE, PsycINFO, Ovid, Cochrane Library, and Google Scholar for placebo-controlled randomized clinical trials, meta-analyses, non-randomized controlled studies, naturalistic studies, case reports, and treatment guidelines published in the past 10 years (2008 to 2017/2018).
  • Focused on potential for abuse and dependence of new and not well-investigated medications in refractory depression and refractory anxiety disorders; using DSM-5, PTSD and OCD were excluded from anxiety disorders except nabilone, which was included because off-label use for anxiety, insomnia, and depression followed PTSD nightmare studies.
  • Excluded other common augmentation strategies in treatment-resistant depression, such as atypical antipsychotics and pramipexole, because the focus was only medications with potential addictive potential.

Limitations

  • Stated in the paper: research on the addictive potential of ketamine, stimulant medications, and nabilone is very limited and the literature is sparse; there is no available research on the addictive potential of ketamine used in depression, no studies on nabilone’s addictive potential, and evidence for cannabis in anxiety and mood disorders is limited to a few single-dose studies.
  • Stated in the paper: key studies have small sample sizes, including a nabilone RCT with only 10 patients, an esketamine follow-up phase with 22 participants of whom only 10 had improvements persisting up to 2 months, and a ketamine meta-analysis of 7 RCTs with small sample size.
  • Evident from the text: this is a narrative/critical review rather than a systematic review with formal quality appraisal; conclusions about long-term dependence are largely hypothetical or based on clinical opinion because long-term data are absent, and the search was restricted to 2008–2017/2018 while excluding some augmentation strategies and PTSD/OCD except nabilone.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.2147/ndt.s167538

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 27 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    There is no research evidence for patients being dependent on prescription stimulant medications in the context of long-term treatment.

    “However, there is no research evidence for patients being dependent on prescription stimulant medications in the context of long-term treatment.”
    Quote in the paperNot a substantial claim
  • Findingreasoning

    There is little research evidence about the potential for addiction of stimulant medications.

    “There is little research evidence about the potential for addiction of stimulant medications, probably because these medications are mostly used in the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents, and the prevailing hypothesis in child psychiatry is that treating ADHD will prevent the development of substance use disorder.”
    Quote in the paperNot a substantial claim
  • Findingnone given

    There have been no studies on the addictive potential of nabilone.

    “There have been no studies on the addictive potential of nabilone.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    In an RCT of 47 patients with treatment-resistant depression, at day 7 after stopping ketamine infusions, only 21 patients still met criteria for response.

    “Another study which failed to demonstrate any long-lasting effects of ketamine was an RCT which included 47 patients with treatment-resistant depression. At day 7 after stopping ketamine infusions, only 21 patients still met the criteria for response.10”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Murrough JW Iosifescu DV Chang LC Antidepressant efficacy of ketamine in treatment resistant major depression: a two-site randomized controlled trial Am J Psychiatry 2013 170 10 1134 1142 23982301 PMC3992936

      Not checked in the free run.

  • Interpretationcitation

    The small sample size in the follow-up phase and small percentage of participants maintaining benefits do not provide convincing evidence of sustained therapeutic benefits of ketamine.

    “This small sample size in the follow-up phase and a small percentage of participants maintaining benefits do not provide convincing evidence of sustained therapeutic benefits of ketamine.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 8
  • May combine two claims. 23

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    There is no available research on the addictive potential of ketamine used in the treatment of depression.

    “There is no available research on the addictive potential of ketamine used in the treatment of depression.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    There is no research evidence on long-term use of stimulant medications in treatment-resistant depression, but in clinical practice there are patients with depression receiving stimulants for a few years or longer.

    “There is no research evidence on long-term use of stimulant medications in treatment-resistant depression, but in clinical practice there are patients with depression receiving stimulants for a few years or longer.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    About 89% of patients relapsed, on average 19 days after receiving 6 infusions of ketamine.

    “About 89% of patients relapsed, on average 19 days after receiving 6 infusions of ketamine.11”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] aan het Rot M Collins KA Murrough JW Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression Biol Psychiatry 2010 67 2 139 145 19897179

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ketamine produces a rapid but transient antidepressant effect, accompanied by brief psychomimetic and dissociative effects.

    “A total of 7 trials with 147 ketamine-treated participants showed that ketamine produced a rapid but transient antidepressant effect, accompanied by brief psychomimetic and dissociative effects.6”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Newport DJ Carpenter LL McDonald WM Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression Am J Psychiatry 2015 172 10 950 966 26423481

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a 4-week placebo-controlled study, a single intravenous dose of ketamine as augmentation of escitalopram in major depressive disorder was safe and effective in speeding up oral antidepressant efficacy, with effects lasting 2 weeks.

    “In a 4 week placebo-controlled study, the efficacy and safety of an intravenous single dose of ketamine as augmentation of escitalopram in major depressive disorder were examined.13 This augmentation strategy was safe and effective in speeding up oral antidepressant efficacy. Effects lasted for 2 weeks, but this study does not provide evidence of sustained benefits as continuous therapy with escit”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Hu YD Xiang YT Fang JX Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study Psychol Med 2016 46 3 623 635 26478208

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    As the benefits of ketamine are short lasting, ongoing treatment with ketamine would be needed for a long time.

    “As the benefits of ketamine are short lasting, ongoing treatment with ketamine would be needed for a long time, similarly to selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and other antidepressants.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Ketamine is effective in the rapid treatment of unipolar and bipolar depression, both as monotherapy and in combination with other medications.

    “Ketamine is effective in the rapid treatment of unipolar and bipolar depression, both as monotherapy and in combination with other medications.7,8”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Fond G Loundou A Rabu C Ketamine administration in depressive disorders: a systematic review and meta-analysis Psychopharmacology (Berl) 2014 231 18 3663 3676 25038867

      Not checked in the free run.

    • cites [8] McGirr A Berlim M Bond D Fleck M Yatham L Lam R A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes Psychol Med 2015 45 4 693 704 25010396

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Treating depression with oral or intranasal ketamine formulations may increase the risk of developing dependence over an extended period, despite the use of much lower doses.

    “As ketamine is a well-known recreational drug that can lead to ketamine dependence, treating depression with oral or intranasal ketamine formulations may increase the risk of developing dependence over an extended period, despite the use of much lower doses.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Ketamine is a well-known recreational drug that can lead to ketamine dependence.

  • May combine two claims.

    Premisecitation

    Ketamine is effective in improving symptoms of major depressive disorder, but its benefits are not sustained.

    “Ketamine is effective in improving symptoms of major depressive disorder, but with no sustained benefits.”
    • Also stated in: § Discussion · plain
      “Ketamine has rapid antidepressant effects, but these effects are short lived and usually last from only a few days to a maximum of 7 days.5”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Williams NR Schatzberg AF NMDA antagonist treatment of depression Curr Opin Neurobiol 2015 36 112 117 26687375

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The only study demonstrating some sustained benefits of intranasal esketamine is an RCT by Janssen; among 22 participants in follow-up, only 10 had improvements in depressive symptoms persisting up to 2 months after stopping esketamine.

    “The only study demonstrating some sustained benefits of intranasal esketamine is an RCT published by the Janssen Research and Development team.14 This study included 67 patients with treatment-resistant depression. Among 22 participants in the follow-up phase, only 10 had improvements in depressive symptoms that persisted up to 2 months after stopping esketamine.14”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Daly EJ Singh JB Fedgchin M Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial JAMA Psychiatry 2018 75 2 139 148 29282469 PMC5838571

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Corp and colleagues concluded that modafinil and armodafinil are effective treatments for treatment-resistant unipolar and bipolar depression.

    “Corp and colleagues carried out a literature review on using stimulants and stimulant alternatives in treating depression and concluded that modafinil and armodafinil are effective treatments for treatment-resistant unipolar and bipolar depression.23”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Corp SA Gitlin MJ Altshuler LL A review of the use of stimulants and stimulant alternatives in treating bipolar depression and major depressive disorder J Clin Psychiatry 2014 75 9 1010 1018 25295426

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Data from randomized clinical trials on methylphenidate and amphetamines are too limited to support the use of stimulants as a first-line augmenting strategy for depression, with the exception of one RCT demonstrating the effects of lisdexamfetamine.

    “Data from randomized clinical trials on methylphenidate and amphetamines are too limited to support the use of stimulants as a first-line augmenting strategy for depression, with the exception of one RCT demonstrating the effects of lisdexamfetamine.23”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Corp SA Gitlin MJ Altshuler LL A review of the use of stimulants and stimulant alternatives in treating bipolar depression and major depressive disorder J Clin Psychiatry 2014 75 9 1010 1018 25295426

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A significant number of ketamine abusers developed dependence after regular use for 1 year, and 53.5% of these abusers reported withdrawal symptoms including fatigue, excessive yawning, aggressive or hostile behavior, anger, irritability, and depression.

    “A significant number of ketamine abusers developed dependence after regular use for 1 year, and 53.5% of these abusers reported withdrawal symptoms including fatigue, excessive yawning, aggressive or hostile behavior, anger, irritability, and depression.18”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Li JH Vicknasingam B Cheung YW To use or not to use: an update on licit and illicit ketamine use Subst Abuse Rehabil 2011 2 11 20 24474851 PMC3846302

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    CANMAT guidelines emphasize that ketamine is associated with psychotomimetic side effects and the potential for abuse, and that there are very limited data on its safety and efficacy with longer term use.

    “The Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of adults with major depressive disorder emphasize that ketamine is associated with psychotomimetic side effects and the potential for abuse, and that there are very limited data on its safety and efficacy with longer term use.19”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Kennedy SH Lam RW McIntyre RS Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments Can J Psychiatry 2016 61 9 540 560 27486148 PMC4994790

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In an Australian open study, stimulants including methylphenidate and dextroamphetamine administered as augmentation were very effective in treating melancholic symptoms for 20% of 50 patients with unipolar or bipolar depression; for 50% of patients in each group, stimulants were somewhat effective and for 30% ineffective.

    “Stimulants, including methylphenidate and dextroamphetamine administered as augmentation, were very effective in treating melancholic symptoms for 20% of patients among the group of 50 patients with unipolar or bipolar depression. For 50% of patients in each group, stimulants were “somewhat effective” and for 30% ineffective.22”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Parker G Brotchie H McClure G Fletcher K Psychostimulants for managing unipolar and bipolar treatment-resistant melancholic depression: a medium-term evaluation of cost benefits J Affect Disord 2013 151 360 364 23810360

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Stimulant medications could address certain residual depressive symptoms, including decreased energy, lack of concentration, decreased alertness, and daytime sleepiness, but these benefits are not sustained and patients lose all of these positive effects after medications are discontinued.

    “Stimulant medications could address certain residual depressive symptoms, including decreased energy, lack of concentration, decreased alertness, and daytime sleepiness, but unfortunately these benefits are not sustained and patients lose all of these positive effects of stimulants after medications are discontinued.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A group of authors from France emphasized that the risk factor for dependence on methylphenidate in children who receive normal doses is the duration of treatment.

    “A group of authors from France emphasized that the risk factor for dependence on methylphenidate in children who receive normal doses is the duration of treatment.31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Chéron-Blumel A Victorri-Vigneau C Hardouin J Methylphenidate prescription: important recommendations to mitigate dependence Neuropsychiatrie de l’Enfance et de l’Adolescence 2012 60 5 S254

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The evidence to support using cannabis in the treatment of anxiety disorders and mood disorders is very limited and includes a few single-dose studies.

    “The evidence to support using cannabis in the treatment of anxiety disorders and mood disorders is very limited and includes a few single-dose studies.36”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Turna J Patterson B Van Amerigan M Is cannabis treatment for anxiety, mood, and related disorders ready for prime time? Depress Anxiety 2017 34 11 1006 1017 28636769

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    These types of withdrawal symptoms provide the best evidence of dependence on stimulants.

    “These types of withdrawal symptoms provide the best evidence of dependence on stimulants.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Cannabis is associated with adverse effects including increased anxiety, psychosis, cognitive impairment, and addiction, which pose significant limitations to using cannabis as a treatment in psychiatry.

    “On the other hand, cannabis is associated with adverse effects including increased anxiety, psychosis, cognitive impairment, and addiction, which pose significant limitations to using cannabis as a treatment in psychiatry.36”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Turna J Patterson B Van Amerigan M Is cannabis treatment for anxiety, mood, and related disorders ready for prime time? Depress Anxiety 2017 34 11 1006 1017 28636769

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In 2015, a group of Canadian military psychiatrists published a randomized placebo-controlled study on the efficacy of nabilone in the treatment of PTSD-associated nightmares; they found a significant reduction in nightmares in the population of military patients with PTSD, with the major limitation of a small sample size of only 10 patients.

    “In 2015, a group of Canadian military psychiatrists published a randomized placebo-controlled study on the efficacy of nabilone in the treatment of PTSD-associated nightmares. They found a significant reduction in nightmares in the population of military patients with PTSD. The major limitation of this study is the small sample size of only 10 patients.41”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Jelty R Heber A Fraser G Boisvert D The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: a preliminary randomized, double-blind, placebo-controlled cross-over design study Psychoneuroendocrinology 2015 51 585 588 25467221

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Among the 20 million Americans who used marijuana in 2013, up to 9% of users may become dependent and this number goes up to 17% if marijuana use is started during adolescence.

    “Among the 20 million Americans who used marijuana in 2013, it was found that up to 9% of users may become dependent and this number goes up to 17% if marijuana use is started during adolescence.34”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Shuman J Hill J Saxon AJ Levin FR Controversies in marijuana legalization: taking the high road MD Conference Express 2015 15 11 12 14

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Frequent cannabis users have a higher prevalence of anxiety disorders, but there is not enough evidence of increased risk for developing long-lasting anxiety disorders in cannabis users.

    “Frequent cannabis users have a higher prevalence of anxiety disorders, but there is not enough evidence of increased risk for developing long-lasting anxiety disorders in cannabis users.38”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Crippa JA Zuardi AW Martín-Santos R Cannabis and anxiety: a critical review of the evidence Hum Psychopharm Clin 2009 24 515 523 19693792

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Long-term and regular use of cannabis for medical conditions could be associated with an even higher rate of cannabis dependence and this medical use is particularly problematic in psychiatric conditions such as anxiety disorders.

    “Long-term and regular use of cannabis for medical conditions could be associated with an even higher rate of cannabis dependence and this medical use is particularly problematic in psychiatric conditions such as anxiety disorders.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    All of these treatments may raise ethical dilemmas about the appropriateness of prescribing these medications in the long run for patients with depression and anxiety disorders.

    “All of these treatments may raise ethical dilemmas about the appropriateness of prescribing these medications in the long run for patients with depression and anxiety disorders.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    There is only one study, published in 2010, saying that reports of nabilone abuse are rare, but the authors recommended a follow-up of patients, including assessment of tolerance and dependence.

    “There is only one study, published in 2010, saying that reports of nabilone abuse are rare, but the authors recommended a follow-up of patients, including assessment of tolerance and dependence.42”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [42] Ware MA Arnaud-Tempe E St The abuse potential of the synthetic cannabinoid nabilone Addiction 2010 105 3 494 503 20402993

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These agents could alleviate patients' suffering in the short run, but their longer use may have undesirable effects, including the possibility of developing tolerance and dependence, and the potential for toxicity with long-term administration.

    “These agents could alleviate patients’ suffering in the short run, but their longer use may have undesirable effects, including the possibility of developing tolerance and dependence, and the potential for toxicity with long-term administration.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    There is a tendency for nabilone or even medicinal cannabis to be prescribed for patients with anxiety, insomnia, and depression, without research evidence of therapeutic effects and with unknown long-term consequences.

    “There is a tendency for nabilone or even medicinal cannabis to be prescribed for patients with anxiety, insomnia, and depression, without research evidence of therapeutic effects and with unknown long-term consequences.37”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Kolar D Kolar MV Critical review of available treatment options for refractory depression and anxiety – clinical and ethical dilemmas Med Pregl 2016 69 5–6 171 176 29693845

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    The risk of dependence with regular use of oral or intranasal ketamine, long-term use of stimulant medication, and synthetic cannabinoids and medicinal cannabis is significant.

    “The risk of dependence with regular use of oral or intranasal ketamine, long-term use of stimulant medication, and synthetic cannabinoids and medicinal cannabis is significant.”
    Quote in the paperNot a substantial claim
29 of 29

  • The paper relies on this without support.

    Benzodiazepines are addictive.

    “It is well known that benzodiazepines are addictive, but we should not forget that these medications were prescribed for decades as a main treatment option for patients with anxiety disorder.”

  • The paper relies on this without support.

    Ketamine is a well-known recreational drug that can lead to ketamine dependence.

    “As ketamine is a well-known recreational drug that can lead to ketamine dependence, treating depression with oral or intranasal ketamine formulations may increase the risk of developing dependence over an extended period, despite the use of much lower doses.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The trend towards off-label prescription of medicinal cannabis/marijuana or nabilone for anxiety disorders may reflect a considerable lag in developing really new and effective evidence-based treatments in anxiety and psychiatry.

    “The noted trend towards the off-label prescription of medicinal cannabis/marijuana or nabilone for patients with anxiety disorders may reflect the fact that there has been a considerable lag in developing really new and effective evidence-based treatments in this field, and in psychiatry in general (Kolar, 2018).”

    From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Kolar, 2018

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Related

Authors
Kolar, D.
ORCID
Kolar, Dusan
Venue
Neuropsychiatric Disease and Treatment
Publisher
Informa UK Limited
Published
2018-06
Volume
Volume 14
Pages
1513-1519
ISSN
  • 1176-6328 (ISSN-L)
  • 1178-2021
DOI
10.2147/ndt.s167538
PMC
PMC6003533
OpenAlex
W2807915416
Semantic Scholar
4f67f499fa4877ea9aef83ede18e9b659aa48437
Cited by
37
References
41
Citations by year
2026: 1 · 2025: 1 · 2024: 6 · 2023: 1 · 2022: 8 · 2021: 4 · 2020: 3 · 2019: 10 · 2018: 3
FWCI
0.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropsychiatric Disease and Treatment (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
treatment-resistant depression, ketamine, synthetic cannabinoids, medical cannabis, benzodiazepine-like effects, major depressive disorder

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