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Sex and Age Differences in Ketamine Efficacy and Safety in Chronic Pain Alleviation.

Gisèle Pickering, Marion Voute, Marc Sorel, Bruno Pereira, Thibault Riant

Journal of Clinical Medicine June 16, 2025 DOI: 10.3390/jcm14124269 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Prospective observational cohort study Peer reviewed
Sample size 585
Population Chronic pain patients
Intervention Ketamine
Duration One year
Topics Depression Ketamine Esketamine
Keywords Refractory pain Sex Ketamine therapy Chronic pain management Depression treatment Clinical study
Citations 2
Key findings No sex or age differences were observed in ketamine efficacy for pain, anxiety, or depression; women reported more adverse events than men.

Abstract

Background: Ketamine use for chronic pain and depression has increased worldwide, but sex differences in its efficacy and safety have been little studied; this study examines existing evidence to address this gap.

Methods: A prospective, multicenter, one-year observational study in 585 chronic pain patients was performed; 256 patients had one administration of ketamine and 329 had two or more. The primary outcome looked at was mean pain intensity (0-10), assessed every month for 1 year by telephone. Secondary outcomes included measures of depression and anxiety (assessed using the Hospital Anxiety and Depression Scale), quality of life (evaluated with the 12-item Short Form Health Survey), total ketamine dosage, reported adverse effects, and concomitant treatments. Platform of Clinical Investigation, No sex or age differences were observed in ketamine efficacy in terms of pain (mean variation in women vs. men; effect size -0.5 (95% confidence interval -0.6 to -0.4) vs. -0.5 (95% confidence interval -0.7 to -0.3), p = 0.248) or the evolution of anxiety (p = 0.135) among the 585 patients. Women reported more adverse events than men (19% vs. 13%, p = 0.002). In the subgroup of 329 patients, no differences were observed in any variables, but a single ketamine administration may be more useful in men than in women (p = 0.032), especially in younger men (p = 0.045).

Conclusions: Repeated ketamine administration displayed no sex or age differences in efficacy in the treatment of pain, anxiety or depression.

Comparable studies

Other observational and cohort studies on ketamine for depression, most cited first.

Study Year Design Participants
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59
Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... 2014 Post hoc analysis of pooled data from four studies n = 108
An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder 2011 Observational cohort n = 14
Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... 2019 Observational cohort n = 25

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