In a clinical setting, ketamine infusions for severe, treatment-resistant mood disorders showed lower response and remission rates than those in research protocols. Of 44 patients starting a four-infusion protocol, 45.5% responded and 27.3% remitted by the fourth infusion. A small long-term subsample (n=14) received 12 to 45 total treatments over 14 to 126 weeks with no observed cognitive decline, increased delusions, or cystitis symptoms. The treatment was generally well tolerated, but the small maintenance group limits conclusions about long-term safety.
Ketamine, originally used as an anesthetic, shows promise as a rapid-acting treatment for severe depression, including treatment-refractory cases. A single dose provides short-lived relief, but multiple infusions may offer sustained effects. Its quick onset could help prevent hospital stays, treat acute suicidal ideation, and facilitate medication changes. Combining ketamine with psychotherapy may enhance response and duration. Despite growing use for various psychiatric disorders, there is inadequate data on true clinical efficacy, safety, and mechanisms of action. This article reviews ketamine's history as an antidepressant, current hypotheses on its mechanisms, and existing evidence on safety and efficacy for clinicians.
For severe treatment-resistant depression, both electroconvulsive therapy (ECT) and ketamine are effective, but it remains unclear which is superior. Two noninferiority trials and three meta-analyses show efficacy for both treatments yet report contradictory findings about which works better. Discrepancies may stem from differences in patient selection, outcome measures, treatment delivery, and site experience. Each treatment has unique risks and benefits that should be weighed for individual patients. The authors aim to help clinicians choose the optimal treatment by evaluating the latest evidence and patient-specific factors.