Abstract
BACKGROUND
Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared to electroconvulsive therapy (ECT), the most effective therapy for depression.
METHODS
Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT, in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery Åsberg Depression Rating Scale [MADRS] score ≤10). Secondary outcomes included adverse events (AEs), time to remission and relapse. Treatment sessions (maximum of twelve) were administered until remission or maximal effect was achieved. Remitters were followed for twelve months after the final treatment session.
RESULTS
186 inpatients were included and received treatment. Among patients receiving ECT 63% remitted, compared to 46% receiving ketamine infusions (p=0.026; difference 95% CI 2%, 30%).
Both ketamine and ECT required a median of six treatment sessions to induce remission. Distinct adverse events (2015) were associated with each treatment. Serious and long-lasting AE, including cases of persisting amnesia, were more common with ECT, while treatment emergent AE led to more dropouts in the ketamine group.
Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within twelve months in the ketamine and ECT group respectively (p=0.52).
CONCLUSION
Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18-85) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.