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Effect of Ketamine on Sleep in Treatment-Resistant Depression: A Systematic Review

Aleksander Kwaśny, A. Włodarczyk, Damian Ogonowski, Wiesław Jerzy Cubała

Pharmaceuticals April 1, 2023 DOI: 10.3390/ph16040568 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Case report Peer reviewed
Population Patients with depression and sleep disturbances
Interventions Ketamine Esketamine
Topics Depression Esketamine Ketamine
Citations 27
Key findings Ketamine reduces the severity of sleep insomnia in depression.

Abstract

Background: Depression is a debilitating disease with a high socioeconomic burden. Regular antidepressants usually require several weeks to ameliorate symptoms; however, numerous patients do not achieve remission. What is more, sleep disturbances are one of the most common residual symptoms. Ketamine is a novel antidepressant with rapid onset of action with a proven antisuicidal effect. Little is known about its impact on sleep–wake and circadian rhythm alterations. The aim of this systematic review is to research the impact ketamine has on sleep disturbances in depression.

Methods: PubMed, Web of Science, and APA PsycINFO were searched for relevant studies on ketamine’s impact on sleep disturbances in depression. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA2020 methodology was applied. The systematic review protocol was registered in the PROSPERO Registry (CRD42023387897).

Results: Five studies were included in this review. Two studies reported significant improvement in sleep measured by MADRS (Montgomery–Åsberg Depression Rating Scale) and QIDS-SR16 (Quick Inventory of Depressive Symptomatology Self-Report (16-item)) scales after intravenous ketamine and intranasal esketamine administration. One case report showed mitigation of symptoms in PSQI (Pittsburgh Sleep Quality Index) and ISI (Insomnia Severity Index) during 3-month treatment with esketamine. In two studies, sleep was objectively measured by nocturnal EEG (electroencephalography) and showed a decrease in nocturnal wakefulness accompanied by an increase in slow wave (SWS) and rapid eye movement (REM) sleep.

Conclusion: Ketamine reduces the severity of sleep insomnia in depression. Robust data are lacking. More research is needed.

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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