Intravenous ketamine versus electroconvulsive therapy for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled trials

Background: Intravenous (IV) ketamine has been evaluated alongside electroconvulsive therapy (ECT) in addressing major depressive disorder (MDD) or bipolar depression (BD), though the comparative outcomes remain inconclusive. This meta-analysis aimed to provide a systematic assessment of the efficacy, safety, and tolerability of IV ketamine relative to ECT for treating MDD or BD.

Methods: Randomized controlled trials (RCTs) comparing IV ketamine and ECT in terms of efficacy, safety, and tolerability for MDD or BD were identified and reviewed. Three independent investigators extracted relevant data, which was synthesized using RevMan 5.3 software under a random effects model.

Results: Five RCTs encompassing 664 patients diagnosed with MDD or BD were analyzed. At 24 h post-initial treatment, IV ketamine demonstrated a statistically greater reduction in depressive symptoms compared to ECT (standardized mean difference (SMD) = -0.53; 95 % CI = -1.03 to -0.04; P = 0.04; I² = 80 %). However, no significant differences were observed between groups in terms of the study-defined response (risk ratio (RR) = 1.49; 95 % CI = 0.08 to 28.42; P = 0.79; I² = 0 %) at 24 h. Similarly, no notable differences were found for depressive symptom improvement (SMD = -0.48; 95 % CI = -2.41 to 1.45; P = 0.63; I² = 99 %), the study-defined response (RR: 0.96, 95 % CI: 0.70 to 1.31; P = 0.79; I² = 75 %) or remission (RR: 0.91, 95 % CI: 0.45 to 1.82; P = 0.78; I² = 90 %) at the end-of-treatment visit. Among the three RCTs (60 %) comparing the neurocognitive outcomes of IV ketamine and ECT through varying test batteries, results were inconsistent. IV ketamine was associated with marked increases in dissociation, blurred vision, dizziness, and diplopia, while ECT led to a significant rise in muscle pain (all Ps < 0.05). Discontinuation rates due to any cause were comparable between both groups (P > 0.05).

Conclusion: IV ketamine demonstrates a faster onset of antidepressant effects compared to ECT, despite both treatments yielding comparable outcomes at the end-of-treatment visit for patients with MDD or BD. However, large-scale RCTs are required to thoroughly evaluate the long-term efficacy and safety of IV ketamine relative to ECT in these populations.