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

Both classical psychedelics (DPT, LSD, psilocybin) and atypical psychedelics (MDMA, ketamine) show promise for reducing anxiety, depression, and existential distress in terminally ill patients, with recent controlled trials indicating positive effects on existential and spiritual well-being, quality of life, and acceptance while causing few adverse and no serious adverse effects. Early studies had serious methodological flaws, but newer trials are of higher quality. Larger high-quality studies are still needed for classical psychedelics and MDMA, and ketamine research should better address existential well-being and psychotherapeutic context.

Study at a glance

Abstract

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. Systematically review studies on psychedelic treatment with and without psychotherapy for existential distress, depression, and anxiety in terminally ill patients. 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. 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. 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.