Background
Electroconvulsive therapy ( ECT) and subanesthetic intravenous ketamine are currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain.
Methods
We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT.
During a 3-week initial treatment phase, patients received ECT three times a week or ketamine (0.5 mg per kilogram of body weight for 40 minutes) twice a week.
The primary outcome was a response to treatment (i.e., a ≥50% decrease from baseline in the 16-item Rapid Inventory of Depressive Symptomatology—Self-Report score; scores range from 0 to 27; higher scores indicate greater depression).
The non-inferiority margin was -10 percentage points. Secondary outcomes included memory test scores and patient-reported quality of life.
Results
A total of 403 patients were randomized at five clinical centers; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients withdrew before starting their assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients.
A total of 55.4% of patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24). .2; P<0.001 for non-inferiority of ketamine versus ECT).
ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in T score for delayed recall on the Hopkins Verbal Learning Test-Revised, −0.9±1.1 in ketamine group vs. −9.7±1.2 in the ECT group; scores range from −300 to 200, with higher scores indicating better function) with gradual recovery during follow-up.
The improvement in patient-reported quality of life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, while ketamine was associated with dissociation.
Conclusions Ketamine was noninferior to ECT as a therapy for treatment-resistant major depression without psychosis. |
(Funded by the Patient-Centered Outcomes Research Institute; ELEKT-D ClinicalTrials.gov number, NCT03113968. opens in new tab.)
