Trial of Psilocybin versus Escitalopram for Depression

Summary & key facts

Researchers ran a carefully controlled study that compared psilocybin with a common antidepressant, escitalopram, in 59 people who had moderate-to-severe depression for a long time. Each person got two doses three weeks apart and six weeks of daily pills; one group got full doses of psilocybin plus placebo pills, the other got tiny psilocybin doses plus daily escitalopram. The main measure after six weeks showed no clear advantage for psilocybin over escitalopram. Some secondary measures, including more people reaching remission, looked better with psilocybin, but those results are preliminary. Side effects were similar in both groups, and the authors say bigger and longer studies are needed.

Key facts:

• Fifty-nine people with long-standing, moderate-to-severe major depression took part in the trial and were put into two groups.
• One group received two full doses of psilocybin (25 mg) three weeks apart and six weeks of daily placebo pills; the other group received two very low psilocybin doses (1 mg) three weeks apart and six weeks of daily escitalopram.
• Neither the patients nor the staff knew who got which treatment while the study was running, which helps reduce bias.
• The main result was the change on a 16-question self-report depression scale after six weeks. Scores fell by about 8 points with psilocybin and by about 6 points with escitalopram. The 2-point difference was not large enough to count as a clear, statistically significant advantage.
• About 70% of people given full-dose psilocybin showed a strong response (more than half reduction in symptoms), compared with about 48% on escitalopram.
• About 57% of the psilocybin group reached remission (a low score on the depression scale) versus about 28% of the escitalopram group, but this finding comes from a secondary comparison that the authors say should be treated cautiously.
• Other secondary outcomes tended to favor psilocybin, but those analyses were not adjusted to account for the many comparisons and so could reflect chance.
• The rate of side effects was similar in both groups in this short, six-week trial.
• The authors conclude that this trial did not prove psilocybin is better than escitalopram on the main outcome, and that larger and longer studies are needed to know more.

Abstract

BACKGROUND: Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking. METHODS: In a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a selective serotonin-reuptake inhibitor, over a 6-week period. Patients were assigned in a 1:1 ratio to receive two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo (psilocybin group) or two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram (escitalopram group); all the patients received psychological support. The primary outcome was the change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16; scores range from 0 to 27, with higher scores indicating greater depression) at week 6. There were 16 secondary outcomes, including QIDS-SR-16 response (defined as a reduction in score of >50%) and QIDS-SR-16 remission (defined as a score of ≤5) at week 6. RESULTS: A total of 59 patients were enrolled; 30 were assigned to the psilocybin group and 29 to the escitalopram group. The mean scores on the QIDS-SR-16 at baseline were 14.5 in the psilocybin group and 16.4 in the escitalopram group. The mean (±SE) changes in the scores from baseline to week 6 were -8.0±1.0 points in the psilocybin group and -6.0±1.0 in the escitalopram group, for a between-group difference of 2.0 points (95% confidence interval [CI], -5.0 to 0.9) (P = 0.17). A QIDS-SR-16 response occurred in 70% of the patients in the psilocybin group and in 48% of those in the escitalopram group, for a between-group difference of 22 percentage points (95% CI, -3 to 48); QIDS-SR-16 remission occurred in 57% and 28%, respectively, for a between-group difference of 28 percentage points (95% CI, 2 to 54). Other secondary outcomes generally favored psilocybin over escitalopram, but the analyses were not corrected for multiple comparisons. The incidence of adverse events was similar in the trial groups. CONCLUSIONS: On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons. Larger and longer trials are required to compare psilocybin with established antidepressants. (Funded by the Alexander Mosley Charitable Trust and Imperial College London's Centre for Psychedelic Research; ClinicalTrials.gov number, NCT03429075.).

Topics

Forensic Toxicology and Drug Analysis Pain Management and Placebo Effect Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Antidepressant Anxiety Depression (economics) Economics Escitalopram Hallucinogen Macroeconomics Medicine Psilocybin Psychiatry Psychology

Substances

Psilocybin

Conditions & symptoms

Anxiety Depression Sadness or low mood