Psilocybin combined with therapy efficacious for depression
Psilocybin combined with therapy was efficacious in treating major depressive disorder, according to results of a randomized clinical trial published in JAMA Psychiatry.
“The combined serotonergic and glutamatergic action of psilocybin (a classic hallucinogen) and the preliminary evidence of the antidepressant effects of psilocybin-assisted therapy (among patients with life-threatening cancer or patients with treatment-resistant depression) indicate the potential of psilocybin-assisted therapy as a novel antidepressant intervention,” Alan K. Davis, PhD, of the department of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, and colleagues wrote. “Moreover, psilocybin has lower addiction liability and toxic effects compared with ketamine and is generally not associated with long-term perceptual, cognitive or neurological dysfunction.”
At a single research center, the investigators conducted the current trial to assess the effect of psilocybin therapy among 24 individuals with MDD aged 21 to 75 years. Participants were not currently using antidepressant medications and had no histories of psychotic disorder, serious suicide attempt or hospitalization. Davis and colleagues randomly assigned participants to either an immediate treatment condition group or delayed treatment condition group. Participants received psilocybin via two sessions in the context of supportive psychotherapy.
Depression severity served as the primary outcome and was assessed via GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline, as well as at weeks 5 and 8 after enrollment for the delayed treatment group, which aligned with weeks 1 and 4 after the intervention for the immediate treatment group. The Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR) served as a secondary outcome.
Results showed a mean baseline GRID-HAMD score of 22.8 among participants who completed the intervention and the week 1 and week 4 post-session assessments. Those in the weeks 1 and 4 immediate treatment group had statistically significantly lower GRID-HAMD scores compared with the scores at the comparable time points of weeks 5 and 8 among the delayed treatment group. Weeks 5 and 8 showed large effect sizes. Results of the QIDS-SR demonstrated a rapid decrease in mean depression score from baseline to the first day after session one. This decrease remained statistically significant through the week 4 follow-up. A total of 16 participants in the overall sample at weeks 1 and 17 and at week 4 exhibited a clinically significant intervention response of a 50% reduction in GRID-HAMD score, and 14 participants at week 1 and 13 participants at week 4 were in remission.
“These data expand the findings of previous studies involving patients with cancer and depression as well as patients with treatment-resistant depression by suggesting that psilocybin may be effective in the much larger population of MDD,” Davis and colleagues wrote. “Further studies are needed with active treatment or placebo controls and in larger and more diverse populations.”
In a related editorial, Charles F. Reynolds III, MD, of the University of Pittsburgh School of Medicine, pointed to several areas of questioning that this research raises, including the role of expectancy effects associated with the extensive psychotherapeutic support and education, as well as whether a double-blind experimental design would produce different results.
“I raise these questions not as criticisms of Davis [and colleagues], but rather to remind clinicians and consumers that panaceas for depression do not exist,” Reynolds wrote. “Instead, I suggest that interventions for depression prevention and treatment must be placed within a staging model across the life cycle, to prevent and treat both early or incident episodes (particularly in the early decades of life) and recurrent episodes (particularly in the middle and later decades of life).”