Psychedelics for the treatment of depression, anxiety, and existential distress in patients with a terminal illness: a systematic review

Background Terminally ill patients may experience existential distress, depression, or anxiety, limiting quality of life in the final stage. Existing psychotherapeutic or pharmacological interventions have (time) limited efficacy. Psychedelic treatment may be a safe and effective alternative treatme...

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Bibliographic Details
Published in:	Psychopharmacology 2022, Vol.239 (1), p.15-33
Main Authors:	Schimmers, Nina, Breeksema, Joost J., Smith-Apeldoorn, Sanne Y., Veraart, Jolien, van den Brink, Wim, Schoevers, Robert A.
Format:	Article
Language:	eng
Subjects:	Anxiety Anxiety - drug therapy Biomedical and Life Sciences Biomedicine Care and treatment Clinical trials Complications and side effects Critically ill Depression - drug therapy Depression, Mental Drug therapy Hallucinogenic drugs Hallucinogens - therapeutic use Humans Ketamine Lysergide MDMA Mental depression Neurosciences Patient outcomes Patients Pharmacology/Toxicology Psilocybin Psilocybin - therapeutic use Psychedelic drugs Psychiatry Psychological aspects Psychotherapy Quality of Life Review Systematic review Terminal illnesses
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Summary:	Background Terminally ill patients may experience existential distress, depression, or anxiety, limiting quality of life in the final stage. Existing psychotherapeutic or pharmacological interventions have (time) limited efficacy. Psychedelic treatment may be a safe and effective alternative treatment option. Aim Systematically review studies on psychedelic treatment with and without psychotherapy for existential distress, depression, and anxiety in terminally ill patients. Methods Medline, PsycINFO, and Embase were searched for original-data studies on the treatment of depression, anxiety, and existential distress with classical or a-typical psychedelics in patients with a terminal illness, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results A total of 1850 records were screened, and 33 articles were included in this review: 14 studies on classical psychedelics (DPT, LSD, and psilocybin) and 19 studies on atypical psychedelics (MDMA and ketamine). Results of early pre-post studies are promising but have serious methodological flaws. Recent (controlled) trials with LSD, psilocybin, ketamine, and MDMA are of higher methodological quality and indicate positive effects on existential and spiritual well-being, quality of life, acceptance, and reduction of anxiety and depression with few adverse and no serious adverse effects. Conclusions Both classical and a-typical psychedelics are promising treatment options in patients with terminal illness. To draw final conclusions on effectiveness and safety of psychedelics, we need larger high-quality studies for classical psychedelics and MDMA. Ketamine studies should pay more attention to existential dimensions of well-being and the psychotherapeutic context of the treatment.
ISSN:	0033-3158 1432-2072