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.
Repeated intravenous ketamine infusions significantly reduced depression, suicidal thoughts, and anxiety in patients with treatment-resistant bipolar I/II depression, and improved functioning. In an observational study of 66 patients receiving four infusions over two weeks, depressive symptoms dropped by an average of 6.08 points on the QIDS-SR16 scale. Response rate was 35% and remission rate 20%. Hypomania occurred in only 4.5% of patients, with no mania or psychosis. The findings suggest real-world effectiveness and tolerability of IV ketamine for bipolar depression.
In a small sample of 31 individuals with treatment-resistant major depressive disorder or bipolar II disorder, those who reported more intense mystical experiences after their first dose of psilocybin-assisted psychotherapy showed greater reductions in depressive symptoms two weeks later. This link between mystical experiences and antidepressant benefit was not observed after the second or third psilocybin doses. The findings offer preliminary support for the idea that mystical-type experiences play a therapeutic role in psilocybin-assisted psychotherapy, extending prior work to a clinically complex population with treatment-resistant depression.