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Side-effects associated with ketamine use in depression: a systematic review.

Brooke L Short, J. Fong, V. Galvez, William Shelker, Colleen Loo

Lancet Psychiatry 2018 DOI: 10.1016/s2215-0366(17)30272-9 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Peer reviewed
Population Patients with depression
Intervention ketamine
Topics Depression Esketamine Ketamine
Citations 551
Key findings After acute dosing, side effects were more frequently reported after ketamine than after placebo, but there is selective reporting bias with limited assessment of long-term safety and repeated dosing.

Abstract

This is the first systematic review of the safety of ketamine in the treatment of depression after single and repeated doses. We searched MEDLINE, PubMed, PsycINFO, and Cochrane Databases and identified 288 articles, 60 of which met the inclusion criteria. After acute dosing, psychiatric, psychotomimetic, cardiovascular, neurological, and other side-effects were more frequently reported after ketamine treatment than after placebo in patients with depresssion. Our findings suggest a selective reporting bias with limited assessment of long-term use and safety and after repeated dosing, despite these being reported in other patient groups exposed to ketamine (eg, those with chronic pain) and in recreational users. We recommend large-scale clinical trials that include multiple doses of ketamine and long-term follow up to assess the safety of long-term regular use.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • After acute dosing, psychiatric, psychotomimetic, cardiovascular, and neurological side effects were more frequently reported with ketamine than placebo, with selective reporting bias and limited long-term safety data.

    Synthesized

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
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
Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review 2021 Systematic review

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