ELEKT-D

Population

• Patients with treatment-resistant major depression without psychosis who were referred to ECT clinics.

Intervention

Ketamine 0.5 mg per kilogram of body weight over 40 minutes twice per week during a 3-week treatment phase.

Comparator

ECT three times per week during the 3-week treatment phase.

Key results

• 403 patients underwent randomization at five clinical sites (200 ketamine, 203 ECT). After 38 withdrew before starting assigned treatment, ketamine was given to 195 and ECT to 170.
• Response: 55.4% with ketamine vs 41.2% with ECT (difference 14.2 percentage points; 95% CI 3.9-24.2; P<0.001 for noninferiority of ketamine to ECT). The noninferiority margin was -10 percentage points.
• As a secondary outcome, ECT was associated with a larger decrease in memory recall after 3 weeks (mean ±SE change in Hopkins Verbal Learning Test-Revised delayed-recall T-score -0.9±1.1 with ketamine vs -9.7±1.2 with ECT), with gradual recovery during follow-up.
• Improvement in patient-reported quality of life, a secondary outcome, was similar in the two groups.

Harms

• ECT was associated with musculoskeletal adverse effects; ketamine was associated with dissociation.
• ECT was associated with a decrease in memory recall after 3 weeks of treatment, with gradual recovery during follow-up.

Practice impact

• For nonpsychotic treatment-resistant depression referred for ECT, ketamine is a noninferior option for short-term response; weigh memory effects of ECT against dissociation with ketamine.

Applicability

• Most applicable to patients with treatment-resistant major depression without psychosis who were referred to ECT clinics and treated for 3 weeks.

Limitations

• Treatment assignment was open-label.
• 38 of 403 randomized patients withdrew before starting assigned treatment (ketamine given to 195, ECT to 170), so randomized and treated Ns differ.
• The trial was designed for noninferiority, not superiority.
• The abstract does not report which analysis set (randomized vs treated) produced the 55.4% and 41.2% response rates.

Common misinterpretations

• Noninferiority is not superiority; do not cite ELEKT-D as proving ketamine is better than ECT.
• This trial excluded psychosis and enrolled patients already referred to ECT clinics; it does not define first-line care for all treatment-resistant depression.