UK: Researchers in a recent study found no significant difference in antidepressant effects between psilocybin and escitalopram.
According to the study, published in the New England Journal of Medicine, psychedelic compound psilocybin did not differ significantly from the antidepressant escitalopram in its effects on severe depression symptoms.
Psychedelic compounds exhibit their action through serotonin receptor (5-HT2A) agonism -- a pathway linked to depression. Psilocybin may have antidepressant properties, but there is a lack of direct comparisons between psilocybin and established treatments for depression. To determine the same, Robin Carhart-Harris, Imperial College London, London, United Kingdom, and colleagues conducted a phase 2, double-blind, randomized, controlled trial involving 59 patients with long-standing, moderate-to-severe major depressive disorder.
The researchers compared psilocybin with escitalopram, a selective serotonin reuptake inhibitor, over a 6-week period. Patients were assigned in a ratio of 1:1 to receive two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo (psilocybin group; n=30) or two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram (escitalopram group; n=29); 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.
Key findings of the study include:
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.
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; QIDS-SR-16 remission occurred in 57% and 28%, respectively, for a between-group difference of 28 percentage points.
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.
"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," wrote the authors.
"Larger and longer trials are required to compare psilocybin with established antidepressants," they concluded.
Reference:
The study titled, "Trial of Psilocybin versus Escitalopram for Depression," is published in the New England Journal of Medicine.
DOI: https://www.nejm.org/doi/full/10.1056/NEJMoa2032994