Psilocybin-assisted psychotherapy (PAP) is feasible for patients with complex, treatment-resistant depression, including those with bipolar II disorder and baseline suicidality. In a randomized trial with 30 adults, those receiving immediate PAP showed greater reductions in depression severity (MADRS) compared to a waitlist control, with a large effect size (Hedge's g = 1.07). Adverse events were transient and no serious adverse events occurred. Repeated doses over six months were associated with further improvement. The findings suggest PAP can be safely delivered to this population and warrants further study.
In a small subgroup analysis of four adults with treatment-resistant depression associated with bipolar II disorder, two 25 mg doses of psilocybin combined with psychotherapy were associated with reductions in depressive symptoms. The average depression score on the Montgomery–Åsberg Depression Rating Scale dropped from 32.5 at baseline to 20.3 two weeks after the first dose, and to 19 two weeks after the second dose; at six months the average score was 21.3. Mania ratings remained stable, and no mania, hypomania, or psychosis occurred. The authors suggest psilocybin may improve depressive symptoms in bipolar II disorder but call for larger studies to confirm the findings.
Both models of psychological intervention in psilocybin-assisted therapy (PAP) may have clinical relevance for treating depression. Future research should standardize reporting of psychological interventions in PAP and use comparative study designs to better evaluate non-specific and specific treatment models, which could inform clinical guidelines.