Sex differences in sub-anesthetic ketamine's antidepressant effects and abuse liability.
Katherine N Wright, Mohamed Kabbaj
Current Opinion in Behavioral Sciences October 2018 DOI: 10.1016/j.cobeha.2018.02.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Dose | sub-anesthetic |
| Topics | Esketamine Ketamine |
| Key findings | The authors conclude that sub-anesthetic ketamine offers rapid, relatively durable antidepressant effects in treatment-resistant bipolar and unipolar depression, with repeated infusions prolonging benefit. They argue that long-term safety, abuse liability, and sex differences in response remain inadequately studied, especially the shortage of preclinical research in females. |
Abstract
Sub-anesthetic ketamine produces rapid antidepressant effects in patients with bipolar and unipolar major depression where conventional monoaminergic-based antidepressant drugs have been ineffective or ridden with side effects. A single ketamine infusion can produce antidepressant effects lasting up to two weeks, and multiple ketamine infusions prolong this effect. Pre-clinical studies are underway to uncover ketamine's mechanisms of action, but there are still many questions unanswered regarding the safety of its long-term use. Abuse liability is one area of concern, as recreational ketamine use is an ongoing issue in many parts of the world. Another understudied area is sex differences in responsivity to ketamine. Women are twice as likely as men to be diagnosed with depression, and they progress through stages of drug addiction more rapidly than their male counterparts. Despite this, preclinical studies in ketamine's antidepressant and addictive-like behaviors in females are limited. These intersecting factors in recent clinical and pre-clinical studies are reviewed to characterize ketamine's therapeutic potential, its limitations, and its potential mechanisms of action.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 6
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers Therapeutic Advances in Psychopharmacology 2020
- A new module in the drug development process: preclinical multi-center randomized controlled trial of R-ketamine on alcohol relapse. Neuropsychopharmacology May 1, 2025
- Registered clinical trials investigating ketamine and esketamine for treatment-resistant depression: A systematic review Journal of Psychedelic Studies January 16, 2023
- Characterizing the therapeutical use of ketamine for adolescent rats of both sexes: Antidepressant-like efficacy and safety profile. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2025
- GluN2B on Adult-Born Granule Cells Modulates (R,S)-Ketamine's Rapid-Acting Effects in Mice. The International Journal of Neuropsychopharmacology October 1, 2024
and 1 more in the library
Cites 11
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- 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
- Ketamine use: a review Addiction July 21, 2011
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders JAMA Psychiatry March 1, 2017
- The use of ketamine as an antidepressant: a systematic review and meta‐analysis Human Psychopharmacology: Clinical and Experimental April 7, 2015
and 6 more in the library