Depression is the most common and disabling mood state in bipolar disorder, yet few effective treatments exist. This review covers emerging therapies, including new atypical antipsychotics lumateperone and cariprazine, which have shown efficacy in large placebo-controlled trials. Non-racemic amisulpride showed potential in one trial needing replication. Intravenous ketamine demonstrated rapid antidepressant and anti-suicidal effects after a single infusion in three small trials. Anti-inflammatory and mitochondrial modulators have inconsistent evidence. Zuranolone, psilocybin, and cannabidiol lack adequately powered trials. While novel agents are on the horizon, further validation and study of patient subgroups are needed.
A living systematic review with meta-analysis examined the efficacy, safety, and all-cause discontinuation of serotonergic psychedelics and MDMA for treating mental disorders. The review found that these substances show promise in reducing symptoms of conditions such as depression, anxiety, and post-traumatic stress disorder, with some evidence supporting their therapeutic potential. However, the authors note that the overall quality of evidence is limited by small sample sizes, short follow-up periods, and methodological concerns. Safety profiles varied, with most adverse events being mild to moderate, though serious adverse events were reported in some studies. The review emphasizes the need for larger, more rigorous trials to confirm these findings.