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.
Citations in the library
Cited by 27
- Harm related to recreational ketamine use and its relevance for the clinical use of ketamine. A systematic review and comparison study Expert Opinion on Drug Safety June 26, 2021
- Ketamine-assisted psychotherapy in adolescents with multiple psychiatric diagnoses. Frontiers in Psychiatry 2023
- Ketamine for mood disorders, anxiety, and suicidality in children and adolescents: a systematic review. European Child & Adolescent Psychiatry 2025
- Parental Attitudes Toward Use of Ketamine in Adolescent Mood Disorders and Suicidality Journal of Child and Adolescent Psychopharmacology October 1, 2021
- Real-world effectiveness of repeated intravenous ketamine infusions for treatment-resistant depression in transitional age youth Journal of Psychopharmacology May 16, 2023
and 22 more in the library
Cites 13
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry 2018
and 8 more in the library