The use of ketamine as an antidepressant: a systematic review and meta-analysis
Coyle, C. M., Laws, K. R.
This meta-analysis (2015; n=437) examined the antidepressant effects of ketamine, with regard to its efficacy over short and long-term periods, across single or repeated infusions, moderating variables related to the experimental design, and efficacy amongst patients with depression (MDD) or bipolar disorder (BD). Results conveyed that ketamine is an effective and rapid treatment for depression in the short term, with large antidepressant effects emerging after 4 hours and lasting up to 2 weeks post-infusion in participants with a primary diagnosis of MDD or BD. Repeated infusion showed larger effect sizes but did not extend the duration of antidepressant effect.
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.