A new study suggests measuring brain activity before starting depression treatment could help doctors predict which patients will experience sexual side effects from antidepressants. The research points to a serotonin-related brainwave pattern that forecast whether a patient might struggle to reach orgasm after taking common SSRIs, and was published in the Journal of Psychiatric Research.
Sexual difficulties are a frequent challenge for people with major depressive disorder. Across the condition’s spectrum, between 40 and 60 per cent experience sexual disturbances. While improving mood can sometimes help the sex life, the medications themselves often create new problems, particularly with desire, arousal and orgasm.
Selective serotonin reuptake inhibitors, or SSRIs, are the most commonly prescribed antidepressants. By increasing serotonin availability in the brain, they can lift depressive symptoms but also frequently hamper sexual function for many individuals, with reports of reduced desire, arousal issues and delayed or absent orgasm.
In the study led by Gudrun Dilja Ketilsdottir and Kristian H. Reveles Jensen, researchers from Copenhagen University Hospital and the University of Copenhagen sought a way to predict who would be most susceptible to these side effects before treatment begins.
The team focused on a biomarker known as the loudness dependence of auditory evoked potentials, measured via electroencephalography. This method records brain activity via scalp sensors while a person listens to sounds that increase in volume, tracking how the brain responds to louder tones.
Previous work suggests this auditory brain response acts as an inverse indicator of central serotonin activity: a weaker brain response to louder sounds may reflect higher baseline serotonin activity. The researchers hypothesised that individuals with elevated serotonin activity before treatment are more likely to cross a threshold when SSRIs are introduced, triggering sexual side effects.
Sixty participants were unmedicated adults with major depressive disorder who completed baseline assessments. They ranged from 18 to 57 years old, with about three-quarters identifying as women. None had used antidepressants for at least two months beforehand.
Before treatment, each participant underwent an EEG while listening to tones across five volume levels, from 60 to 100 decibels. Researchers used these responses to calculate the auditory brain response for each person, alongside baseline sexual function questionnaires and blood testosterone measurements.
Initially, 86 of the participants began eight weeks of escitalopram, with seven patients switching to the antidepressant duloxetine due to inadequate response or intolerance by week four.
At the eight-week mark, clinicians assessed the severity of any medication-induced sexual side effects. The researchers then applied statistical models to determine whether pretreatment brain wave measurements could predict the observed side effects.
The analysis revealed a robust link: patients with weaker pretreatment brain responses to increasing sound volume experienced higher rates of orgasmic dysfunction after starting SSRIs. The brain pattern predicted distressing orgasmic dysfunction with about 87 per cent accuracy.
There was also an association with reduced sexual desire, but it was only marginal compared with the strong link to orgasmic dysfunction. Importantly, the brain marker did not relate to erectile dysfunction in the male participants.
When testosterone levels measured before treatment were included in the predictive models, they did not significantly alter the accuracy. In other words, the auditory brain response alone, together with basic demographics and baseline sexual function, sufficed for prediction.
The researchers found that the brain response did not correlate with sexual dysfunction caused by depression itself, but rather with the body’s reaction to the introduction of SSRI medication. They propose that the marker captures the specific serotonergic pathway disrupted by SSRIs, whereas libido likely involves a broader network of brain chemicals.
Limitations include an open-label design without a placebo control, meaning some observed changes could reflect natural fluctuations in illness rather than the medication alone. The average participant age was 27.5, which may limit applicability to older populations.
Additionally, a minority of participants switched from escitalopram to duloxetine partway through the trial, meaning two different antidepressants were studied. A secondary analysis focusing only on those on escitalopram yielded the same outcome, but the authors emphasise that testing the brain marker against a single, standardised medication would bolster conclusions.
Looking ahead, the researchers plan to evaluate the biomarker in more diverse patient groups within routine clinical settings. If validated across broader populations, the test could become a standard screening tool to identify patients at high risk of SSRI sexual side effects and guide the selection of antidepressants that act on different brain systems.
The study, “Serotonergic activity estimated by EEG loudness-dependent auditory evoked potentials as a predictor of sexual SSRI side effects,” was authored by Gudrun Dilja Ketilsdottir, Cheng-Teng Ip, Vibe G. Frokjaer, Annamaria Giraldi, Martin Balslev Jørgensen, and Kristian H. Reveles Jensen.
