Ketamine for unipolar depression: A systematic review of efficacy and safety.
Tharshanan Edwin Peiris, Amrit Pokhrel, Yuvaraj Paudel
Australasian Psychiatry June 1, 2025 DOI: 10.1177/10398562251328805 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Formally diagnosed individuals with unipolar depression |
| Interventions | Ketamine Esketamine |
| Topics | Depression Ketamine Esketamine |
| Keywords | Efficacy Rapid-acting antidepressant Safety Unipolar depression Ketamine therapy Rapid antidepressants Mental health treatments Depression medication |
| Citations | 2 |
| Key findings | Ketamine significantly reduces depressive symptoms and suicidal ideation within hours in treatment-resistant unipolar depression, with effects lasting up to one week. |
Abstract
BackgroundUnipolar depression is a prevalent mental health disorder with persistent, treatment-resistant symptoms. Traditional antidepressants take weeks to show effects, underscoring the need for faster alternatives. Ketamine, originally an anaesthetic, has emerged as a rapid-acting antidepressant.ObjectiveThis systematic review evaluates ketamine's efficacy and safety in unipolar depression.MethodsA literature search (January 2000-May 2024) in PubMed, PsycINFO, and Cochrane Library included RCTs, CCTs, systematic reviews, meta-analyses, and observational studies on ketamine or esketamine in formally diagnosed individuals. Study characteristics, interventions, outcomes, and adverse events were analyzed, with quality and bias assessments.ResultsAcross 44 studies, ketamine significantly reduced depressive symptoms and suicidal ideation within hours, particularly in treatment-resistant cases, with effects lasting up to 1 week. Common side effects included transient dissociation, elevated blood pressure, nausea, and dizziness, while long-term safety remains uncertain.ConclusionsKetamine shows promise as a rapid antidepressant for treatment-resistant unipolar depression. However, long-term safety and optimal treatment protocols require further research. Careful clinical integration with monitoring is recommended.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for depression, most cited first.
Citations in the library
Cited by 2
- Age-related moderation of adjunctive psychotherapy and early life stress effects on depression symptom reductions following ketamine treatment: Initial insights from a large, naturalistic sample. Journal of Affective Disorders February 4, 2026
- Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders. CNS Spectrums September 28, 2026
Cites 37
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- 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
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
and 32 more in the library