Major Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Bipolar DisorderDepressive DisordersKetaminePlacebo

Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression

This meta-analysis (2015) of six randomised, double-blind, placebo-controlled trials (n=101) examined the short-and mid-term efficacy of ketamine (bipolar) to depression. Ketamine effectively reduced symptoms in unipolar depression for seven days, , whereas the maintenance of its efficacy in bipolar depression failed to reach significance after 4 days.

Authors

  • Romeo, B.
  • Choucha, W.
  • Fossati, P.

Published

Psychiatry Research
meta Study

Abstract

Introduction

Among treatments currently assessed in major depression, ketamine, has been proposed of great interest, especially because of its very rapid action. However, the time-course of the antidepressive action of ketamine remained unclear. In the present meta-analysis, we provided a clear and objective view regarding the putative antidepressive effect of ketamine and its time-course.

Methods

We searched the MEDLINE and PsycINFO databases through December 2013, without limits on year of publication, using the key words ketamine and synonyms for mood disorder or episode. Six randomized, double-blind and placebo-controlled trials of ketamine in major depression (n=103 patients) were thus identified. Authors were contacted and they all provided original data necessary for this meta-analysis. Standardized mean differences (SMD) were calculated between the depression scores in ketamine and placebo groups at days 1, 2, 3-4, 7 and 14.

Results

Ketamine showed an overall antidepressive efficacy from day 1 to day 7. However, the maintenance of its efficacy over time failed to reach significance in bipolar depression after day 3-4. Significant SMDs were not explained by demographic or clinical characteristics of included samples.

Discussion

The present meta-analysis provides a high level of evidence that ketamine has a rapid antidepressive action during one week, especially in unipolar disorder.

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Research Summary of 'Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression'

Introduction

Major depression is common, disabling and often slow to respond to conventional monoaminergic antidepressants, prompting interest in treatments that act more rapidly. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist that modulates the glutamatergic system, has been reported to produce marked antidepressant effects within hours of a single dose. However, the clinical literature is heterogeneous with small samples, mixed diagnoses (unipolar versus bipolar), differing outcome measures and variable follow-up times, so the time-course and reliability of ketamine’s antidepressant action remained unclear. Romeo and colleagues therefore carried out a meta-analysis to provide a quantitative, time-resolved estimate of ketamine’s efficacy in treatment‑resistant depression. The study aimed to compare ketamine with placebo on depression scores at prespecified time points (day 1, day 2, day 3–4, day 7 and day 14) and to explore whether demographic or clinical sample characteristics (age, sex, illness duration, episode duration, comorbidities, prior treatment) or route of administration influenced effect sizes. This work sought to address gaps in prior meta-analyses, particularly the lack of detailed time-course analyses based on continuous depression scores.

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Study Details

References (8)

Papers cited by this study that are also in Blossom

Antidepressant effects of ketamine in depressed patients

Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)

Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy

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A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression

Diazgranados, N., Ibrahim, L., Brutsche, N. E. et al. · JAMA Psychiatry (2010)

943 cited
Ketamine and other potential glutamate antidepressants

Dutta, A., Mckie, S., Deakin, J. F. W. · Psychiatry Research (2014)

Ketamine administration in depressive disorders: a systematic review and meta-analysis

Fond, G., Loundou, A., Macgregor, A. et al. · Psychopharmacology (2014)

Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial

Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)

Relationship of ketamine’s antidepressant and psychotomimetic effects in unipolar depression

Sos, P., Klirova, M., Novák, T. et al. · Neuropsychiatric Disease And Treatment (2013)

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Zarate, C. A., Brutsche, N. E., Ibrahim, L. et al. · Biological Psychiatry (2012)

757 cited

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Bobo, W. V., Vande Voort, J. L., Croarkin, P. E. et al. · Depression and Anxiety (2016)

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