The use of ketamine as an antidepressant: a systematic review and meta‐analysis

Ketamine infusion produces a significant antidepressant effect in people with major depressive disorder and bipolar disorder, with effects appearing within 4 hours and lasting up to 7 days after a single dose. Repeated infusions produce larger effects than single infusions at 4 hours, 24 hours, and 7 days. The proportion of male participants predicted a stronger antidepressant response at 7 days. Peak response time may differ by diagnosis: 24 hours for major depressive disorder and 7 days for bipolar disorder. Results from studies at 12–14 days did not reach significance. Most published studies used pre–post comparisons; more placebo-controlled studies are needed.

Study at a glance

Abstract

Objective The current meta‐analysis examines the effects of ketamine infusion on depressive symptoms over time in major depressive disorder (MDD) and bipolar disorder (BD). Methods Following a systematic review of the literature, data were extracted from 21 studies ( n = 437 receiving ketamine) and analysed at four post‐infusion time points (4 h, 24 h, 7 days and 12–14 days). The moderating effects of several factors were assessed including: repeat/single infusion, diagnosis, open‐label/participant‐blind infusion, pre–post/placebo‐controlled design and the sex of patients. Results Effect sizes were significantly larger for repeat than single infusion at 4 h, 24 h and 7 days. For single infusion studies, effect sizes were large and significant at 4 h, 24 h and 7 days. The percentage of males was a predictor of antidepressant response at 7 days. Effect sizes for open‐label and participant‐blind infusions were not significantly different at any time point. Conclusions Single ketamine infusions elicit a significant antidepressant effect from 4 h to 7 days; the small number of studies at 12–14 days post infusion failed to reach significance. Results suggest a discrepancy in peak response time depending upon primary diagnosis — 24 h for MDD and 7 days for BD. The majority of published studies have used pre–post comparison; further placebo‐controlled studies would help to clarify the effect of ketamine over time. Copyright © 2015 John Wiley & Sons, Ltd.