For patients with treatment-resistant depression, is a single dose of psilocybin effective at improving symptoms?
At 3 weeks, a single 25-mg dose of psilocybin provided a clinically meaningful benefit for patients with treatment-resistant depression (NNT for remission = 5). However, the benefit was not well sustained at 12 weeks. Further study is needed to establish the optimal dose and frequency of treatment.
Plan de l'etude:
Randomized controlled trial (double-blinded)
Psilocybin, a psychedelic compound found in some mushrooms, has been synthesized into a pharmaceutical-grade compound. These researchers identified adults who were experiencing an episode of treatment-resistant depression based on failure to respond to 2 to 4 adequate trials of antidepressants. At baseline, their mean age was 40 years, 52% were women, 92% were White, 86% had been experiencing their current episode for longer than 1 year, and all had moderate to severe depression based on the Hamilton Depression Scale. Groups were balanced at baseline and analysis was by modified intention to treat that included all patients with at least one outcome assessment. The 233 patients were randomized to receive either 1 mg, 10 mg, or 25 mg psilocybin in a single dose. The 1-mg group was considered unlikely to report any effect and was used as the control. The primary outcome was the change in the Montgomery–Åsberg Depression Rating Scale (MADRS), a 60-point scale where an improvement of at least 6 points would be considered clinically significant. At 3 weeks, the improvement in the MADRS score was 12 points in the 25-mg group, 7.9 points in the 10-mg group, and 5.4 points in the 1-mg group. The difference between the 25-mg group and the 1-mg group was clinically and statistically significant (-6.6 points; 95% CI -2.9 to -10.2). Remission, defined as a 50% reduction in the MADRS score, also occurred significantly more often in the 25-mg group than the 1-mg group at 3 weeks (37% vs 18%; odds ratio [OR] 2.9; 1.2 - 6.6; number needed to treat [NNT] = 5). At 12 weeks, a sustained response was not seen significantly more often in the 25-mg group than in the 1-mg group (20% vs 10%; OR 2.2; 0.9 - 5.4). There were no statistically or clinically significant benefits seen in the 10-mg group compared with the 1-mg group. There were no important differences in severe adverse events among the groups, although nonsevere headache and nausea were more common in the 25-mg group.
Mark H. Ebell, MD, MS
University of Georgia