The impact of sex as a biological variable in the search for novel antidepressants.
Alexia V Williams, Brian C Trainor
Frontiers in neuroendocrinology July 2018 DOI: 10.1016/j.yfrne.2018.05.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Monoamine-based antidepressants Ketamine |
| Topics | Depression Ketamine |
| Keywords | Antidepressants Kappa opioid receptor Oxytocin social behavior Sex differences |
| Key findings | The authors argue that sex is an important biological variable modulating the efficacy of antidepressants and anxiolytics, and that similar behavioral effects between sexes may arise through sex-specific neurobiological mechanisms, as appears to be the case for ketamine. They conclude that both males and females should be included in clinical and preclinical evaluations of novel antidepressants and anxiolytics. |
Abstract
A roadblock to successful treatment for anxiety and depression is the high proportion of individuals that do not respond to existing treatments. Different underlying neurobiological mechanisms may drive similar symptoms, so a more personalized approach to treatment could be more successful. There is increasing evidence that sex is an important biological variable modulating efficacy of antidepressants and anxiolytics. We review evidence for sex-specific effects of traditional monoamine based antidepressants and newer pharmaceuticals targeting kappa opioid receptors (KOR), oxytocin receptors (OTR), and N-methyl-D-aspartate receptors (ketamine). In some cases, similar behavioral effects are observed in both sexes while in other cases strong sex-specific effects are observed. Most intriguing are cases such as ketamine which has similar behavioral effects in males and females, perhaps through sex-specific neurobiological mechanisms. These results show how essential it is to include both males and females in both clinical and preclinical evaluations of novel antidepressants and anxiolytics.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cited by 6
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- Registered clinical trials investigating ketamine and esketamine for treatment-resistant depression: A systematic review Journal of Psychedelic Studies January 16, 2023
- Clinical Predictors of Antidepressant Effects of Ketamine and Esketamine in Treatment-Resistant Unipolar and Bipolar Depression: A Systematic Review CNS Drugs July 1, 2026
- Perspective Chapter: Ketamine, Depression, and Gender Bias Ketamine Revisited - New Insights into NMDA Inhibitors September 14, 2022
- Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status. CNS Drugs May 1, 2021
and 1 more in the library
Cites 15
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- 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
- Better Biomarkers, Faster Drugs, Stronger Models: Progress Towards Precision Psychiatry. Missouri medicine 2023
and 10 more in the library