Ketamine is a rapid and effective treatment for adults with treatment-resistant depression, but different formulations and routes of delivery vary in effect size. A meta-analysis of studies found that intranasal ketamine or esketamine had a large effect on depression symptoms at 24 hours and again at 7-20 days. Intravenous ketamine or esketamine showed a large but not statistically significant effect at 2-6 days. Oral ketamine had a moderate effect at 21-28 days. No conclusions about which formulation or route is best could be drawn because direct comparisons are lacking. More studies with larger samples are needed, especially for oral ketamine.
Psychedelics like psilocybin and MDMA show promise as a new type of therapy for mental health disorders. Evidence suggests they may work with just one dose, produce rapid effects, and be effective for treatment-resistant conditions, possibly serving as a standalone treatment. More clinical trials are needed to test their safety, tolerability, and effectiveness in real-world patient populations.
A review of preclinical and clinical studies indicates that dextromethorphan (DXM) is well tolerated and shows clinically significant antidepressant effects; DXM combined with bupropion has demonstrated replicated and relatively rapid onset efficacy in adults with major depressive disorder (MDD). Preliminary reports also suggest efficacy in adults with bipolar depression. The combination represents a pharmacokinetic and pharmacodynamic synergy that may account for its rapid action. The authors consider DXM/bupropion a safe, well tolerated, and efficacious treatment option for adults with MDD, and highlight the relevance of glutamate as a treatment target. Priority questions include whether it is uniquely effective across discrete domains of psychopathology and whether it can improve patient-reported outcomes.