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Ketamine for mood disorders, anxiety, and suicidality in children and adolescents: a systematic review

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Abstract

Mood disorders, anxiety, and suicidality in youth are increasing and rapid-acting treatments are urgently needed. One potential is ketamine or its enantiomer esketamine, which was FDA approved in 2019 to treat major depressive disorder with suicidality in adults. This systematic review evaluated the evidence for the clinical use of ketamine to treat mood disorders, anxiety, and suicidality in youth. The PRISMA guidelines were used, and a protocol registered prospectively (https://osf.io/9ucsg/). The literature search included Pubmed/MEDLINE, Ovid/MEDLINE, Scopus, CINAHL, PsychInfo, and Google Scholar. Trial registries and preprint servers were searched, and authors contacted for clarification. Studies reported on the clinical use of ketamine to treat anxiety, depression, bipolar disorder, or suicidality in youth ≤19 years old and assessed symptoms before and after ketamine use. Study screening and data extraction were conducted independently by 2–4 authors. Safety, tolerability, and efficacy data were collected. The Cochrane Risk of Bias guidelines assessed the quality of the evidence. Twenty-two published reports based on 16 studies were identified: 7 case studies, 6 observational studies, 3 randomized trials, and 6 secondary data analyses. Studies reported immediate improvements in depression, anxiety, and suicidality. Improvements were maintained for weeks-months following treatment. Ketamine was well-tolerated with the most common side effects being dizziness, nausea, and mild dissociation. Transient hemodynamic changes were reported, all of which resolved quickly and did not require medical intervention. Initial evidence suggests ketamine is safe and may be effective for mood disorders, anxiety, and suicidality in youth. Further randomized trials are warranted.

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Funding

Dr. Bruton and Dr. Johnstone are supported by the Center for Mental Health Innovation at Oregon Health & Science University through unrestricted philanthropic funding, and Dr. Johnstone is also supported by grants from NIH (NIH-NCCIH K2390281846). Dr. Marshall is supported by Oregon Health & Science University and receives funding through the Oregon Health Authority. Mr. Wesemann was supported by Oregon Health & Science University and through an unrestricted philanthropic grant. Dr. Machingo and Mr. Majak have no funding to report.

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Authors and Affiliations

  1. Oregon Health & Science University, Portland, OR, USA

    Alisha M. Bruton, Dalton G. Wesemann, Taryn A. Machingo, Jeanette M. Johnstone & Rebecca D. Marshall

  2. University of Lethbridge, Lethbridge, Canada

    Gop Majak

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  1. Alisha M. Bruton
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  2. Dalton G. Wesemann
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Contributions

Rebecca Marshall and Dalton Wesemann conceptualized this work; Alisha Bruton performed the literature searches; Alisha Bruton, Gop Majak, Taryn Machingo, and Dalton Wesemann extracted the data; Alisha Bruton prepared the original draft; and Alisha Bruton, Gop Majak, Taryn Machingo, Dalton Wesemann, Jeanette Johnstone, and Rebecca Marshall reviewed and edited the work. Funding was obtained and supervision provided by Rebecca Marshall and Jeanette Johnstone.

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Correspondence to Alisha M. Bruton.

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This is a systematic review. As such it contained only de-identified, publicly available data, and was therefore not subject to ethics approval or oversight.

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Bruton, A.M., Wesemann, D.G., Machingo, T.A. et al. Ketamine for mood disorders, anxiety, and suicidality in children and adolescents: a systematic review. Eur Child Adolesc Psychiatry (2024). https://doi.org/10.1007/s00787-024-02458-y

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