A randomized clinical trial of adjunctive ketamine anesthesia in electroconvulsive therapy for depression

Background: Electroconvulsive therapy (ECT) is a rapid acting and effective treatment for both major depressive disorder (MDD) and bipolar disorder (BP). Both propofol and ketamine are commonly used anesthetic agents but recent clinical studies suggest that ketamine has rapid-acting antidepressant properties, itself, at sub-anesthetic doses. Methods: A total of 77 inpatients (41 MDD and 36 BP) were randomly assigned to receive ECT with propofol (1 mg/kg) anesthesia or with ketamine (0.5 mg/kg) plus propofol (0.5 mg/kg). Depressive symptoms were assessed with the 24-item Hamilton Depression Rating Scale (HAMD-24) and Montgomery-Asberg Rating Scale (MADRS), before and after 1, 2, 4, and 6 ECT treatments, and 1-4 weeks following the last treatment. The MATRICS Consensus Cognitive Battery (MCCB) was evaluated at baseline, after the sixth ECT, and 1-4 weeks following the final ECT. Adverse effects were assessed at baseline and 4 weeks after the last treatment. Results: There were no significant differences in depressive symptoms, MCCB performance, or adverse effects between the treatment groups at any time. The electrical dose required to generate seizures in the ketamine plus propofol group was lower than that of the propofol only group at every time point. The seizure energy index and seizure duration in the ketamine plus propofol group was higher and longer than those in the propofol only group. Limitations: The diagnoses of MDD and BP were unevenly distributed across treatment groups. Conclusions: Ketamine plus propofol anesthesia in the ECT treatment of MDD and BP was not superior on any measure to propofol alone.