Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 32301056 · doi:10.1007/s43440-020-00097-z
What was done
Systematic literature search across Medline, Embase, Cochrane Library, and Trip Database up to February 22, 2019, to identify peer-reviewed randomized controlled trials evaluating single and repeated ketamine administration in patients with major depression (unipolar and bipolar). Eligible studies were appraised and pooled in a meta-analysis.
What was found
A total of 20 RCTs were analyzed. Single-dose ketamine demonstrated its largest reduction in depressive symptoms versus controls at 24 hours (SMD = -0.89; 95% CI: -1.24 to -0.53; p < 0.00001), remaining significant up to 7 days in treatment-resistant patients and as add-on therapy, but not as monotherapy at 7 days. Repeated dosing maintained therapeutic effects at 2–3 weeks versus placebo (SMD = -0.70, 95% CI: -1.15 to -0.25, or SMD = -0.81, 95% CI: -1.41 to -0.20, depending on dosing regimen; p <= 0.009).
Why it matters
While single-dose ketamine produces rapid relief that typically wanes quickly, this meta-analysis provides pooled RCT evidence that repeated administration regimens can sustain antidepressant gains for up to 3 weeks.
Limits
The abstract does not state the total participant sample size, specific routes of administration, or details on control comparators (e.g., active placebo vs. saline). Adverse effects, tolerability, and durability beyond 3 weeks were not reported in the abstract.
Cited by
- supports Ketamine demonstrates immediate and profound antidepressant effects in treatment-resistant depressed patients, but these effects are short-lived.