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Ketamine for unipolar depression: A systematic review of efficacy and safety.

Tharshanan Edwin Peiris, Amrit Pokhrel, Yuvaraj Paudel

Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists 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.

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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