OPEN Foundation

R. Schoevers

Is ketamine an appropriate alternative to ECT for patients with treatment resistant depression? A systematic review

January 21, 2022 / Depression, Ketamine, Papers, Psychiatry / Leave a Comment / By / , , , ,

Abstract

Objective: Ketamine has repeatedly shown to have rapid and robust antidepressant effects in patients with treatment resistant depression (TRD). An important question is whether ketamine is as effective and safe as the current gold standard electroconvulsive therapy (ECT).

Methods: The literature was searched for trials comparing ketamine treatment with ECT for depression in the Pubmed/MEDLINE database and Cochrane Trials Library.

Results: A total of 137 manuscripts were identified, 6 articles were included in this review. Overall quality of the included studies was diverse with relevant risk of bias for some of the studies. Results suggest that ketamine treatment might give faster but perhaps less durable antidepressant effects. Side effects differed from ECT, in particular less cognitive impairment was apparent in ketamine treatment.

Limitations: The included studies have limited sample sizes, use different treatment protocols and in most trials, longer term follow up is lacking. Furthermore, allocation bias appears likely in the non-randomized trials.

Conclusions: Current available literature does not yet provide convincing evidence to consider ketamine as an equally effective treatment alternative to ECT in patients with TRD. There are indications for a more favourable short term cognitive side effect profile after ketamine treatment. Methodologically well-designed studies with larger sample sizes and longer follow up duration are warranted.

Veraart, J., Smith-Apeldoorn, S. Y., Spaans, H. P., Kamphuis, J., & Schoevers, R. A. (2021). Is ketamine an appropriate alternative to ECT for patients with treatment resistant depression? A systematic review. Journal of affective disorders, 281, 82–89. https://doi.org/10.1016/j.jad.2020.11.123

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Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

August 17, 2020 / Addiction, Anxiety disorders / PTSD, Ayahuasca, Depression, HPPD, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , ,

Abstract

Introduction: Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. Processes that may affect therapeutic change are not yet fully understood. Qualitative research methods are increasingly used to examine patient accounts; however, currently, no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders.

Objective: To provide an overview of salient themes in patient experiences of psychedelic treatments for mental disorders, presenting both common and diverging elements in patients’ accounts, and elucidating how these affect the treatment process.

Methods: We systematically searched the PubMed, MEDLINE, PsycINFO, and Embase databases for English-language qualitative literature without time limitations. Inclusion criteria were qualitative research design; peer-reviewed studies; based on verbalized patient utterances; and a level of abstraction or analysis of the results. Thematic synthesis was used to analyze and synthesize results across studies. A critical appraisal of study quality and methodological rigor was conducted using the Critical Appraisal Skills Programme (CASP).

Results: Fifteen research articles, comprising 178 patient experiences, were included. Studies exhibited a broad heterogeneity in terms of substance, mental disorder, treatment context, and qualitative methodology. Substances included psilocybin, lysergic acid diethylamide (LSD), ibogaine, ayahuasca, ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Disorders included anxiety, depression, eating disorders, post-traumatic stress disorder, and substance use disorders. While the included compounds were heterogeneous in pharmacology and treatment contexts, patients reported largely comparable experiences across disorders, which included phenomenological analogous effects, perspectives on the intervention, therapeutic processes and treatment outcomes. Comparable therapeutic processes included insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum, which patients reported contributed to clinically and personally relevant responses.

Conclusions: This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances, and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders.

Breeksema, J. J., Niemeijer, A. R., Krediet, E., Vermetten, E., & Schoevers, R. A. (2020). Psychedelic treatments for psychiatric disorders: a systematic review and thematic synthesis of patient experiences in qualitative studies. CNS drugs, 1-22; 10.1007/s40263-020-00748-y

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[Psychedelics in the treatment of substance use disorders and psychosis]

August 1, 2020 / Addiction, Anxiety disorders / PTSD, Depression, Ketamine, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Psychotherapy, Publications / By / , , ,

Abstract

After psychedelics were banned in 1968, the flourishing research on the use of psychedelics in patients with a mental disorder stopped abruptly. Recently, we see a renaissance of this research.<br/> AIM: To present an overview of what is known about the treatment of addiction and psychosis with psychedelics.<br/> METHOD: Literature study based on Medline en PubMed publications till December 2019.<br/> RESULTS: Studies on the effectiveness of psychedelics in the treatment of addiction and psychosis is still very limited in size and methodological quality. Nevertheless, most studies show positive effects of both classical and atypical psychedelics in a variety of addictions on motivation, craving, reduced consumption, and abstinence often following a single dose and with long-lasting benefits (3-24 months). Use of ketamine in patients with a psychosis stabilized on an antipsychotic might reduce negative symptoms.<br/> CONCLUSION: Before psychedelics can be used in standard clinical practice for the treatment of patients with an addiction or a psychosis, larger and methodologically better studies are needed. The use of psychedelics also creates an opportunity to better understand the shared underlying pathology of many different mental disorders.
van den Brink, W., Breeksema, J. J., Vermetten, E., & Schoevers, R. A. (2020). Psychedelics in the treatment of substance use disorders and psychosis. Tijdschrift Voor Psychiatrie, 62(8), 650-658., https://pubmed.ncbi.nlm.nih.gov/32816293/
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[Psychedelics for existential distress in terminally ill patients]

August 1, 2020 / Anxiety disorders / PTSD, Depression, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , ,

Abstract

Existential distress in patients with a terminal illness is often associated with (symptoms of) anxiety and depression. Psychotherapeutic interventions seem effective but effects are short-lived. There are no proven effective pharmacological interventions.<br/> AIM: To present an overview of literature on psychedelic treatment of existential distress in patients with terminal illness.<br/> METHOD: Literature research in PubMed/Medline databases, supplemented with cross-references.<br/> RESULTS: 14 clinical studies have been conducted: 6 with classic psychedelics between 1960 and 1980, and 8 with classic psychedelics and ketamine after 2000. Results of early pre-post studies are promising but have serious methodological limitations. Recent clinical research with LSD, psilocybin and ketamine are also promising although limited in terms of research design and generalizability. Overall, studies show a positive effect on existential and spiritual well-being, quality of life, acceptance and (symptoms of) anxiety and depression. Mystical experiences are correlated with positive outcomes. Few adverse effects are reported.<br/> CONCLUSION: Treatment of existential distress using classical psychedelics or ketamine in patients with terminal illness seems auspicious. Larger clinical studies in a more diverse patient population with fewer methodological limitations are needed to draw conclusions about efficacy and generalizability.
Schimmel, N., Breeksema, J. J., Veraart, J. K. E., van den Brink, W., & Schoevers, R. A. (2020). Psychedelics for existential distress in terminally ill patients. Tijdschrift Voor Psychiatrie, 62(8), 659-668., https://europepmc.org/article/med/32816294
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[Psychedelics in the treatment of PTSD]

August 1, 2020 / Anxiety disorders / PTSD, Depression, Ketamine, LSD, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , ,

Abstract

Posttraumatic stress disorder (PTSD) is often a chronic condition, despite the availability of various evidence-based treatment options. Psychedelics offer new treatment opportunities.<br/> AIM: An overview of the current evidence, therapeutic context, and possible mechanisms of action of different types of psychedelics in the treatment of PTSD.<br/> METHOD: A scoping review of the available literature.<br/> RESULTS: MDMA-assisted psychotherapy has shown to produce lasting reductions in PTSD symptoms in multiple RCTs. Based on a small number of studies, ketamine administration appears to lead to temporary symptom relief. Current studies are investigating whether the use of ketamine in combination with psychotherapy can lead to lasting reductions in PTSD symptoms. Classical psychedelics (such as psilocybin and LSD) induce psychoactive effects (on behavior or experience) that could contribute to the psychotherapeutic treatment of PTSD but have not yet been investigated in controlled studies. Reported positive effects extend beyond PTSD symptoms only.<br/> CONCLUSION: Psychedelics may have potential to serve as a catalyst for the psychotherapeutic treatment of PTSD. Most evidence exists for MDMA-supported psychotherapy; relatively little research is available on ketamine and classical psychedelics. Future research needs to show whether the use of psychedelics can be integrated into available treatment options for PTSD.
Vermetten, E., Krediet, E., Bostoen, T., Breeksema, J. J., Schoevers, R. A., & van den Brink, W. (2020). Psychedelics in the treatment of PTSD. Tijdschrift Voor Psychiatrie, 62(8), 640-649., https://pubmed.ncbi.nlm.nih.gov/32816292/

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Oral ketamine for the treatment of pain and treatment-resistant depression

February 1, 2016 / Depression, Ketamine, Papers, Psychiatry, Psychology, Publications / By / , , , ,

Abstract

Background

Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications.

Aims

To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain.

Method

Searches in PubMed with the terms ‘oral ketamine’, ‘depression’, ‘chronic pain’, ‘neuropathic pain’, ‘intravenous ketamine’, ‘intranasal ketamine’ and ‘subcutaneous ketamine’ yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality.

Results

Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects.

Conclusions

Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials.

Schoevers, R. A., Chaves, T. V., Balukova, S. M., aan het Rot, M., & Kortekaas, R. (2016). Oral ketamine for the treatment of pain and treatment-resistant depression. The British Journal of Psychiatry, 208(2), 108-113. http://dx.doi.org/10.1192/bjp.bp.115.165498

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30 April - Q&A with Rick Strassman

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