Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis

Meta-analysis (n=436, from 7 of 9 nine included studies) showed a significantly greater efficacy of psilocybin compared with comparator treatment among patients with secondary depression (Hedges’ g=1.64, 95% CI 0.55-2.73, p<0.001) based on change in depression scores.

SPS commentary:

Researchers note that since the early 2000s, the naturally occurring serotonergic hallucinogen psilocybin, found in several species of mushrooms, has been widely discussed as a potential treatment for depression. Its mechanism of action differs from that of classic SSRIs and it is suggested it might improve treatment response rate, decrease time to improvement of symptoms, and prevent relapse post-remission. It has also been claimed that more recent assessments of harm have consistently reported that psilocybin generally has low addictive potential and toxicity and can be administered safely under clinical supervision.

An editorial points out variability between studies was considerable (I2=89.7%) and not meaningfully lower in any of the subgroup analyses, and despite a lenient assessment of risk of bias and quality of evidence, the certainty supporting a strong antidepressant effect of psilocybin was judged to be low. It also notes that the meta-analysis could not answer several questions:

  1. it could not provide evidence for effectiveness in depression (performance under real world conditions) until more information about potential effect modifiers is gathered.
  2. there is still ongoing debate about whether psychedelics can express antidepressant activity on their own rather than by assisting specific forms of psychotherapy.
  3. little information existed about long term (>8 weeks) benefits of psilocybin in people with depression.
  4. It could not differentiate between those individuals most likely to benefit from psilocybin and those who might experience adverse events.

It adds that conversely, suggestions that psychedelics such as psilocybin cause only negligible side effects contrast with concerning reports of confusional states, substance misuse, intentional self-harm, suicidal behaviour, and psychotic symptoms, especially in people with pre-existing vulnerability.

It concludes these promising findings support a prudent approach in both scholarly and public settings, because more and better evidence is needed before any clinical recommendation can be made about therapeutic use of psilocybin.

British Medical Journal

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Editorial