Ketamine and its enantiomer esketamine show promise for quickly relieving suicidal thoughts in unipolar and bipolar depression, but the evidence is weak. An overview of 26 systematic reviews and 44 randomized controlled trials involving 3,316 subjects found the intervention effective and well-tolerated, but the quality of the included reviews and original studies is poor, resulting in low certainty of evidence. Insufficient data prevent differentiation between effects in unipolar versus bipolar depression. Enhanced methodological rigor in future research is needed to inform treatment guidelines.
This protocol describes an upcoming overview of reviews that will analyze existing systematic reviews and meta-analyses of randomized clinical trials on psilocybin therapy. The goal is to evaluate the therapeutic effects, safety profiles, and adverse effects of psilocybin across various psychiatric conditions diagnosed according to ICD-10 or DSM-5-TR criteria. The study will compare psilocybin therapy against placebo, no treatment, or standard drug therapies. The authors note the need to consolidate scattered evidence from the growing body of psilocybin research, which could inform future clinical applications and policy.