Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode : A Systematic Review and Meta-analysis

Importance  Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episode remains unknown.

Objective  To systematically review and meta-analyze data about clinical efficacy and safety for ketamine and ECT in patients with major depressive episode.

Data Sources  PubMed, MEDLINE, Cochrane Library, and Embase were systematically searched using Medical Subject Headings (MeSH) terms and text keywords from database inception through April 19, 2022, with no language limits. Two authors also manually and independently searched all relevant studies in US and European clinical trial registries and Google Scholar.

Study Selection  Included were studies that involved (1) a diagnosis of depression using standardized diagnostic criteria, (2) intervention/comparator groups consisting of ECT and ketamine, and (3) depressive symptoms as an efficacy outcome using standardized measures.

Data Extraction and Synthesis  Data extraction was completed independently by 2 extractors and cross-checked for errors. Hedges g standardized mean differences (SMDs) were used for improvement in depressive symptoms. SMDs with corresponding 95% CIs were estimated using fixed- or random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed.

Main Outcomes and Measures  Efficacy outcomes included depression severity, cognition, and memory performance. Safety outcomes included serious adverse events (eg, suicide attempts and deaths) and other adverse events.

Results  Six clinical trials comprising 340 patients (n = 162 for ECT and n = 178 for ketamine) were included in the review. Six of 6 studies enrolled patients who were eligible to receive ECT, 6 studies were conducted in inpatient settings, and 5 studies were randomized clinical trials. The overall pooled SMD for depression symptoms for ECT when compared with ketamine was −0.69 (95% CI, −0.89 to −0.48; Cochran Q, P = .15; I2 = 39%), suggesting an efficacy advantage for ECT compared with ketamine for depression severity. Significant differences were not observed between groups for studies that assessed cognition/memory or serious adverse events. Both ketamine and ECT had unique adverse effect profiles (ie, ketamine: lower risks for headache and muscle pain; ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, and transient dissociative/depersonalization symptoms). Limitations included low to moderate methodological quality and underpowered study designs.

Conclusions and Relevance  Findings from this systematic review and meta-analysis suggest that ECT may be superior to ketamine for improving depression severity in the acute phase, but treatment options should be individualized and patient-centered.

Key Points

Question  Is ketamine as effective as electroconvulsive therapy (ECT) in patients with major depressive episode?

Findings  This systematic review and meta-analysis of 6 trials with 340 patients suggests that ECT may be superior to ketamine in improving depression severity. Findings also suggest that ketamine and ECT each have unique adverse effect profiles.

Meaning  Although ECT may be more efficacious than ketamine in the acute phase, treatment options should be individualized and patient-centered, considering different adverse effect profiles and patient preferences.