Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.
Level 4 - case-series / case-control
Open-label single-arm feasibility study without a control group (case series)
PubMed 27210031 · doi:10.1016/S2215-0366(16)30065-7
What was done
In an open-label feasibility trial, 12 patients (6 men, 6 women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after dosing. The primary feasibility measure was patient-reported intensity of psilocybin effects, alongside adverse reaction monitoring. Depressive symptoms were assessed from 1 week to 3 months post-treatment using the 16-item Quick Inventory of Depressive Symptoms (QIDS) as the primary efficacy outcome.
What was found
Psilocybin acute effects peaked at 2–3 hours and subsided by 6 hours. Mean self-rated intensity (0–1 scale) was 0.51 (SD 0.36) for 10 mg and 0.75 (SD 0.27) for 25 mg. No serious or unexpected adverse events occurred; observed adverse effects included transient anxiety during onset (12/12), transient confusion or thought disorder (9/12), mild transient nausea (4/12), and transient headache (4/12). Relative to baseline, depressive symptoms decreased at 1 week (mean QIDS difference -11.8, 95% CI -9.15 to -14.35, p=0.002, Hedges' g=3.1) and at 3 months (mean difference -9.2, 95% CI -5.69 to -12.71, p=0.003, Hedges' g=2). Improvements in anxiety and anhedonia were also reported without numerical values.
Why it matters
This study provides initial evidence of safety and potential efficacy for psilocybin assisted by psychological support in treatment-resistant depression, laying groundwork for randomized trials.
Limits
The study was open-label without a control group and had a very small sample size (n=12), preventing definitive separation of drug effects from psychological support, placebo responses, or natural recovery. Follow-up was limited to 3 months.
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.