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

Abstract

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.

Pattern Breaking: A Complex Systems Approach to Psychedelic Medicine

“…Recent evidence suggests that psychedelic therapy may lead to significant and sustained antidepressant and anxiolytic effects, even for individuals with treatment-resistant depression (Fauvel, Strika-Bruneau and Piolino, 2021;Hesselgrave et al 2021;Muttoni, Ardissino and John, 2019;Carhart-Harris et al, 2018b;Stroud et al 2018). Good results have also been seen in cases with high suicidality and psychological distress linked to terminal illness (Schimmel et al 2021).…”

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“…The tables below show pharmacokinetic parameters for different doses of LSD based on compartmental modeling. …”