Psilocybin with psychological support for treatment-resistant depression: six-month follow-up.

In an open-label trial, twenty patients with severe, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, one week apart) in a supportive setting. Depressive symptoms dropped markedly within the first five weeks, with large effect sizes (Cohen's d = 2.2 at week 1 and 2.3 at week 5). Nine patients responded and four achieved remission at week 5. Improvements remained significant at three and six months (Cohen's d = 1.5 and 1.4). No one sought conventional antidepressants within five weeks. The quality of the acute psychedelic experience predicted symptom reductions at five weeks. Tolerability was good, and psilocybin appears promising for unresponsive depression, though double-blind trials are needed.

Study at a glance

Abstract

RATIONALE: Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. OBJECTIVES: Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. METHODS: Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure. RESULTS: Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. CONCLUSIONS: Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.