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The effectiveness, safety and tolerability of ketamine for depression in adolescents and older adults: A systematic review.

Joshua D. Di Vincenzo, Ashley N. Siegel, Orly Lipsitz, R. Ho, Kayla M Teopiz, Jason Ng, Leanna M.W. Lui, Kangguang Lin, Bing Cao, Nelson B Rodrigues, Hartej Gill, Roger S McIntyre, Joshua D. Rosenblat

Journal of Psychiatric Research March 1, 2021 DOI: 10.1016/j.jpsychires.2021.02.058 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Randomized Open-label Peer reviewed
Sample size 13
Population Adolescents (age ≤18) and older adults (age ≥60) with clinically diagnosed depression
Intervention Ketamine
Topics Depression Esketamine Ketamine
Citations 59
Key findings Ketamine produced rapid antidepressant effects (≤2 weeks) in ten of thirteen studies, with better outcomes from larger, repeated doses and open-label designs, but the limited quantity and quality of evidence precludes strong conclusions.

Abstract

The majority of antidepressant medication trials have focused on adult populations (ages 18-65), with much less research in older and younger populations. Moreover, key differences in the efficacy and safety of antidepressants have been identified between these age groups. Ketamine has emerged as a promising new treatment for treatment resistant depression (TRD). The objective of this review is to summarize and synthesize the extant literature on the effectiveness, safety and tolerability of ketamine for depression in special age populations (age ≤18 and ≥ 60). Following PRISMA guidelines, a systematic review was performed, searching EMBASE, PsycInfo, and PubMed from inception through July 2020. Studies reporting the use of any ketamine formulation with variable routes of administration to treat clinically diagnosed depression in adolescents or older adults were included. Thirteen studies were included in the analysis and ten observed rapid (≤2 week latency) antidepressant effects following ketamine treatments, with better outcomes following larger, repeated doses, and in open-label rather than blinded settings. Two case reports in adolescents assessed measures of suicidal ideation and both found ketamine to effectuate rapid anti-suicidal effects. Ketamine appears to be safe and well-tolerated in adolescents and older adults. The small quantity, high heterogeneity, and generally low quality of available studies precludes statistical syntheses and significantly limits the strength of our conclusions. Preliminary proof-of-concept studies are promising, however, rigorously designed randomized controlled trials (RCTs) are still required to ascertain effectiveness, safety and tolerability in these groups.

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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