Psilocybin with psychological support for treatment-resistant depression: six-month follow-up.
Level 4 - case-series / case-control
Open-label, single-arm clinical trial with no control group.
PubMed 29119217 · doi:10.1007/s00213-017-4771-x
What was done
Twenty patients (six females) with mostly severe, unipolar, treatment-resistant major depression enrolled in an open-label trial. Participants received two oral doses of psilocybin (10 mg and 25 mg, spaced 7 days apart) in a supportive psychological setting. Depressive symptoms were evaluated from 1 week to 6 months post-treatment using the self-rated 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) as the primary outcome measure.
What was found
Treatment was reported to be well tolerated. Compared with baseline, depressive symptoms decreased markedly at week 1 (Cohen's d = 2.2, p < 0.001) and week 5 (Cohen's d = 2.3, p < 0.001). At week 5, nine patients achieved clinical response and four achieved remission, and no patients sought conventional antidepressants within the first 5 weeks. Symptom reductions remained statistically significant at 3 months (Cohen's d = 1.5, p < 0.001) and 6 months (Cohen's d = 1.4, p < 0.001). Reductions in symptoms at week 5 were predicted by the quality of the acute psychedelic experience.
Why it matters
This study provides early preliminary evidence that psilocybin combined with psychological support can produce rapid, large, and sustained antidepressant effects lasting up to 6 months in patients unresponsive to standard treatments.
Limits
The trial was open-label with a very small sample size (n = 20) and lacked a placebo or active comparator arm, making it impossible to rule out expectancy effects, placebo response, or natural disease fluctuation. Long-term follow-up lacked control for post-study interventions or confounding variables.
Cited by
- supports The first patient in the psilocybin trial who had previously failed numerous antidepressants achieved full remission and remained well.
- supports Robin Carhart-Harris conducted a clinical trial of psilocybin for treatment-resistant depression in 20 participants, some of whom had previously tried up to 14 antidepressant medications.