The Use of Ketamine as an Antidepressant: A Systematic Review and Meta-Analysis

Hum Psychopharmacol. 2015 May;30(3):152-63. doi: 10.1002/hup.2475. Epub 2015 Apr 7.

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.

Keywords: bipolar disorder; depression; ketamine; major depressive disorder.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / therapeutic use
  • Bipolar Disorder / drug therapy*
  • Depressive Disorder, Major / drug therapy*
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Female
  • Humans
  • Infusions, Intravenous
  • Ketamine / administration & dosage
  • Ketamine / therapeutic use*
  • Male
  • Sex Factors
  • Time Factors

Substances

  • Antidepressive Agents
  • Excitatory Amino Acid Antagonists
  • Ketamine