A new study published in the Journal of Psychiatric Research has found that a simple brain measurement taken before treatment begins may predict which patients will experience sexual dysfunction from antidepressant medications. The findings suggest that individuals with naturally higher levels of serotonin activity are significantly more susceptible to these side effects, particularly difficulties with reaching orgasm.
Depression is a debilitating condition that frequently impacts sexual health, with symptoms often including reduced desire and satisfaction. While effective treatment with antidepressants usually improves mood and overall well-being, the medications themselves can introduce new sexual challenges.
Selective serotonin reuptake inhibitors are the most commonly prescribed class of antidepressants. They are known to cause sexual side effects in a large percentage of users. These adverse effects can range from decreased libido to an inability to ejaculate or reach orgasm.
These complications present a significant barrier to effective treatment. Many patients discontinue their medication because the sexual side effects affect their quality of life, self-esteem, and relationships.
Currently, psychiatrists rely on a trial-and-error approach when prescribing these drugs. There is no standard clinical method to determine in advance who will tolerate a specific medication well and who will develop severe side effects. Two patients with similar depression profiles might take the same dose of the same drug, yet have vastly different physical reactions.
“Sexual side effects are one of the most troublesome problems with antidepressants, affecting up to 70% of patients taking SSRIs. These side effects, particularly difficulty reaching orgasm and reduced libido, make patients concerned about starting medication, and often cause people to stop their medication, which can be dangerous for their mental health,” said study author Kristian Høj Reveles Jensen, a postdoctoral at the Neurobiology Research Unit at Copenhagen University Hospital.
“The frustrating thing is that we can’t predict who will experience these problems in advance. Two patients might take the same antidepressant at the same dose, but one has no sexual side effects, whilst the other develops distressing side effects. We suspected this variability might be related to differences in brain chemistry, specifically the amount of serotonin activity before starting treatment.”
The study utilized data from the NeuroPharm-1 clinical trial. The research team recruited 90 adults who had been diagnosed with a moderate to severe depressive episode. The participants ranged in age from 18 to 56 years. The majority of the sample was female, making up 73 percent of the group.
Strict inclusion criteria ensured that the participants were appropriate for the study. All subjects were free of antipsychotic medication and had not taken any antidepressants for at least two months prior to the start of the trial. This washout period ensured that the baseline measurements would not be influenced by lingering medication effects. A certified psychiatrist confirmed all diagnoses according to standard medical classification systems.
Before receiving any medication, each participant underwent an electroencephalogram recording session. This procedure involves placing sensors on the scalp to detect electrical activity in the brain. The researchers measured a specific response known as the loudness dependence of the auditory evoked potential. During the test, participants listened to a series of tones played at five different intensities, ranging from 60 to 100 decibels.
The brain’s electrical response to these increasing volumes provides insight into serotonin activity. Previous research has established an inverse relationship between this electrical response and central serotonin levels. A strong increase in electrical activity as the sound gets louder indicates low serotonin activity. Conversely, a weak or flat response to the increasing volume suggests high serotonin activity. This established biomarker allowed the researchers to estimate each patient’s baseline serotonin function without invasive procedures.
Following the initial testing, the patients began an eight-week treatment regimen with escitalopram. This drug is a standard selective serotonin reuptake inhibitor. Doses were adjusted individually between 5 and 20 milligrams per day, depending on how well the patient responded and what side effects they reported.
Sexual function was assessed at the beginning of the study and again after eight weeks using validated questionnaires. Clinicians also conducted structured interviews to rate the severity of any side effects and determine whether they were likely caused by the medication.
The researchers found an association between the pretreatment brain measurements and the development of sexual side effects. Patients who exhibited a weaker response to the auditory tones—indicating higher baseline serotonin activity—experienced significantly more severe orgasmic dysfunction after eight weeks of treatment. This relationship held true even when the researchers statistically adjusted for age, sex, and any sexual problems the patients had related to their depression before treatment started.
The predictive power of the model increased when the researchers combined the EEG data with the patients’ pretreatment reports of sexual symptoms. This combined approach allowed the model to predict distressing sexual side effects with 87 percent accuracy. This level of precision is substantial for a psychiatric biomarker. It suggests that the test could be clinically useful in identifying those at high risk.
The researchers also found that the brain measurement was specifically predictive of medication-induced side effects rather than general sexual health. The EEG scores did not correlate with the patients’ sexual function before they started the medication.
“What surprised us most was how specific the prediction was,” Jensen told PsyPost. “The EEG measure wasn’t related to sexual function before treatment; it only predicted treatment-emergent sexual side effects. This suggests we’re measuring something about how the brain will respond to SSRIs, not just general vulnerability in sexual function.”
The researchers also investigated whether testosterone levels played a role in predicting these side effects. Blood samples were taken to measure plasma testosterone before treatment. However, adding testosterone data to their statistical models did not improve the accuracy of the predictions. The EEG measurement of serotonin activity remained the primary predictor of outcome.
When examining the specific types of sexual dysfunction, the biomarker was more strongly associated with difficulties in reaching orgasm than with decreased libido. This aligns with biological understandings of the serotonin system.
The ability to reach orgasm is known to be directly influenced by specific serotonin receptors. Sexual desire, in contrast, involves a more complex interplay of various neurotransmitters, including dopamine. The specificity of the finding lends support to the idea that the EEG test is measuring a relevant biological mechanism.
The study also highlighted differences in how men and women experience these side effects. Consistent with broader medical literature, a higher proportion of women in the study had sexual dysfunction prior to treatment compared to men.
During treatment, clinicians and patients generally agreed on the presence of side effects. However, women were more likely to report distressing sexual side effects that clinicians did not attribute as strongly to the medication. In men, there was near-perfect agreement between the patient’s report and the clinician’s assessment.
“We found that a simple 30-minute EEG test before starting antidepressants can predict who is most likely to develop sexual side effects,” Jensen explained. “Patients with naturally higher serotonin activity, measured by lower LDAEP scores, had a much higher risk of experiencing sexual side effects from SSRIs, particularly difficulty reaching orgasm.”
“When we combined the EEG test with information about any sexual symptoms patients already had from their depression, we could predict sexual side effects with 87% accuracy. This could help doctors and patients make more informed choices about which antidepressant to try first.”
While the results are promising, there are some limitations to consider. The sample size of 90 patients is relatively small for a clinical study intended to change practice standards. The gender imbalance, with a high preponderance of female participants, means the results may be less precise for male patients. The confidence intervals for the predictions in men were wider, indicating less certainty in that subgroup.
Another limitation is the accessibility of the technology. While an electroencephalogram is less expensive than brain imaging scans, it is not currently a standard piece of equipment in most psychiatric outpatient clinics. Implementing this testing as a routine procedure would require significant investment in equipment and training.
“It is essential to note that while the EEG test shows great promise, it is not yet widely available in clinical settings and is largely limited to research contexts,” Jensen told PsyPost. “We are working towards making this test more accessible to healthcare providers in the near future.”
The study was also open-label, meaning both the patients and doctors knew which medication was being administered. This design can sometimes introduce bias in how side effects are reported. However, the objective nature of the pretreatment EEG measurement helps mitigate this concern regarding the biological findings.
The researchers note that the results do not suggest patients with high serotonin activity should avoid antidepressants entirely. “Rather, it gives clinicians and patients better information for shared decision-making,” Jensen said. “For some, the mood benefits might outweigh the sexual side effects. For others, knowing their risk is high might prompt choosing an antidepressant with a different mechanism, like bupropion or mirtazapine, which have lower rates of sexual side effects. This is about precision treatment—using biology to inform, not dictate, clinical decisions.”
“Also, we need to sort out what we mean by sexual side effects. Libido is very context-dependent, and the causes of changes in libido are difficult to quantify and predict. SSRIs do, in a dose-dependent manner, change the ability to reach orgasm, and this was easier to predict with our EEG measure. A slight delay in reaching orgasm/ejaculation may be welcomed for some male patients or be non-distressing or a minor side effect compared to the mood benefit from the drug.”
“Overall, we see that patients taking SSRIs improve their general sexual functioning after 2-3 months because the depression is treated,” Jensen continued. “When their mood improves, they start having more sex, and the side effects become noticeable.”
“We’re currently running a much larger study, called BrainDrugs-Depression, with 600 patients to replicate and extend these findings. If confirmed, the next step would be to develop standardised protocols for implementation in clinical practice. We’re also interested in whether this biomarker could help predict other SSRI side effects. The broader goal is moving psychiatry from “trial and error” to “predict and personalise” by using objective brain measures to help match patients with the treatments most likely to help them, whilst minimising side effects.”
“This work was led by our medical student, Gudrun Dilja Ketilsdottir, who will help us validate the findings in our larger study,” Jensen added.
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.
