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Is ketamine effective and safe for treatment-resistant depression?

Amanda Zorn, Sean Linn, Mat Jenkinson, Jon O Neher, Sarah Safranek, Gary Kelsberg

The Journal of family practice April 1, 2021 DOI: 10.12788/jfp.0176 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Meta-analysis of randomized controlled trials Peer reviewed
Population Patients with depression, including treatment-resistant major depression
Interventions Oral ketamine Intranasal esketamine spray
Duration 1-3 days to 6 weeks
Topics Depression Esketamine Ketamine
Citations 5
Key findings Ketamine and esketamine show short-term efficacy for depression, but evidence is limited by small, low-quality trials and significant adverse effects.

Abstract

MAYBE, but it's too soon to tell. There is limited evidence that ketamine by itself is effective in the very short term. Single-dose intravenous (IV) ketamine is more likely than placebo (odds ratio = 11-13) to produce improvement (> 50%) in standardized depression scores in 1 to 3 days, lasting up to a week. Twice- or thriceweekly IV ketamine improves symptom scores by 20%-25% over 2 weeks (strength of recommendation [SOR]: B, meta-analysis of small, low-quality, randomized controlled trials [RCTs] and a single small RCT).Augmentation of sertraline with daily oral ketamine moderately improves symptom scores for 6 weeks in patients with moderate depression (SOR: B, small, lowquality RCTs).Augmentation of oral antidepressants (duloxetine, escitalopram, sertraline, venlafaxine) with intranasal esketamine spray improves response and remission rates at 4 weeks (16% for both outcomes) in patients with predominantly treatment-resistant major depression (SOR: A, meta-analysis of RCTs).Ketamine therapy is associated with confusion, emotional blunting, headache, dizziness, and blurred vision (SOR: A, metaanalyses).Nasal esketamine spray produces the adverse effects of dizziness, vertigo, and blurred vision severe enough to cause discontinuation in 4% of patients; it also can produce transient elevation of blood pressure (SOR: A, meta-analyses).

Comparable studies

Other systematic reviews and meta-analyses on ketamine for depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
The use of ketamine as an antidepressant: a systematic review and meta‐analysis People with major depressive disorder or bipolar disorder receiving ketamine infusion 2015 Meta-analysis n = 437

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