A brain test may predict antidepressant-related sexual problems, early research suggests

By Kristen Rogers, CNN

(CNN) — Going on antidepressants can give many people their life back, but for some there is a catch. About 25% to 80% of people who take antidepressants experience sexual side effects to some degree during treatment.

Now, a tool may one day help patients both feel better and keep their sex life intact, early research suggests.

Even though cases of antidepressant-induced sexual dysfunction have been documented since 1960, there has never been a way to predict the odds of problems with libido, arousal, orgasm, erectile function or other sexual functions before someone starts taking an antidepressant.

That uncertainty eventually may change with the new use of a brain test that indirectly measures levels of the critical neurotransmitter serotonin — which is involved in libido, arousal, mood, appetite, sleep, memory and social behavior.

The novel application of the existing test is described in preliminary, first-of-its-kind research to be presented Tuesday at the 38th ECNP (European College of Neuropsychopharmacology) Congress in Amsterdam. The research is currently an abstract, so it’s still under peer review before it will be published in a journal.

If the findings are replicated in studies with more participants, they “could enable a more precise approach to depression treatment,” lead researcher Dr. Kristian Jensen said in a news release.

Such testing could help doctors select medications to minimize risk of sexual side effects in patients most likely to experience them, said Jensen, a physician and postdoctoral researcher at the neurobiological research unit of Copenhagen University Hospital and Mental Health Services Centre Copenhagen.

How the brain test works

The noninvasive test is an electroencephalogram, or EEG, which involves placing small electrodes on the scalp to record electrical activity in the brain.

The test captures a specific biomarker called Loudness Dependence of Auditory Evoked Potentials, or LDAEP, which measures the brain’s electrical activity in response to sound. Auditory perception is dependent upon the brain’s serotonin levels since the neurotransmitter regulates the processing of sensory information including sound, Jensen told CNN.

The lower the LDAEP level, the greater the serotonin activity. After serotonin does its job in the brain, nerve cells reabsorb it. The common antidepressant escitalopram and others that are selective serotonin reuptake-inhibitors, or SSRIs, work by limiting the brain’s reuptake, making more serotonin available for use in regulating mood. Though this increase can be beneficial for mood, it’s also one of the mechanisms thought to cause antidepressant-related sexual dysfunction.

Previous studies have suggested the LDAEP marker may be worth investigating in people with mental health conditions such as depression, bipolar disorder and anxiety, in that LDAEP levels may help predict how well a patient will respond to different psychiatric medications.

Researchers behind the latest science studied 90 participants with major depressive disorder and found lower LDAEP measures (which means higher serotonin levels) predicted orgasmic dysfunction from eight weeks of treatment with escitalopram with 87% accuracy.

Jensen and others are currently working on a similar study with 600 participants.

The measure didn’t significantly predict reduced libido but was slightly associated with the severity of antidepressant-related decreased libido. And regardless of what participants’ LDAEP measures were, they didn’t translate to differences in baseline sexual function before antidepressant treatment, further suggesting the medication caused the sexual dysfunction.

The precise treatment approach Jensen and his colleagues described “could help treatment adherence and overall quality of life and generally give better treatment options for depression,” he added. “We need a bigger study, with more men, to get an accurate figure for erectile dysfunction.”

The participants were unmedicated prior to treatment, age 27 on average and mostly female. To measure LDAEP, the researchers played “sounds at different volumes through headphones while measuring brain waves,” Jensen said in the news release. “It takes about 30 minutes and is non-invasive. It’s not generally available at the moment, but that may change if this test lives up to expectations.”

Though early, the research is promising and could be quite useful, said Dr. Josef Witt-Doerring, a psychiatrist and CEO and medical director of TaperClinic, who wasn’t involved in the study. He and other clinicians help patients experiencing complex withdrawal syndromes and tapering off psychiatric drugs.

However, “there are clear caveats,” said psychiatrist Dr. Sameer Jauhar, a clinical associate professor in affective disorders and psychosis at Imperial College London, in a written statement provided by the Science Media Centre. Jauhar wasn’t involved in the study.

The LDAEP measure “is not a direct measure of serotonin activity,” Jauhar said. “It is not measuring it in the way we generally measure neurotransmitters in the brain, i.e. through molecular imaging, such as PET.”

But PET scans are invasive, costly and time-consuming, Jensen told CNN. “Nonetheless, our research unit has used PET to demonstrate that LDAEP is associated with serotonin levels,” he added. “The relationship between LDAEP and serotonin goes back several decades of human and animal research. It’s rare to find a biomarker that is both scientifically robust and practically accessible.”

Additionally, the predictive accuracy requires clarification in a peer-reviewed publication, Jauhar added. “Sometimes smaller sample sizes can inflate this, and it needs validation in another dataset.” A placebo-controlled study would also be ideal, both Jauhar and Jensen said.

Antidepressants and sexual function

At least 11.4% of adults in the United States took antidepressants in 2023 for depression alone. Millions more take them for other mental health issues including anxiety, post-traumatic stress disorder, some eating disorders, substance use disorder and obsessive-compulsive disorder. (Information on global estimates of antidepressant use is lacking.)

The science behind antidepressant-induced sexual dysfunction boils down to neurotransmitters, blood flow and the muscular system, all of which are controlled by the brain, experts told CNN in a 2024 report.

What’s necessary for physical arousal and orgasm is increased blood flow to the genitalia, which makes nerve endings in these organs more sensitive, Dr. Lauren Streicher, founding medical director of the Northwestern Medicine Center for Sexual Medicine and Menopause, told CNN in 2024. These factors send signals to the brain that result in the muscle contractions accompanied by orgasm.

Higher levels of serotonin in the brain and other areas involved in sex can inhibit those functions, said Streicher — since SSRIs potentially restrict blood flow by binding to alpha-1 adrenergic receptors, which are found in blood vessels in the skin, brain and more. The receptors control constriction and dilation in the smooth muscle fibers in the walls of these blood vessels.

Since not everyone taking these medications experiences sexual dysfunction even with higher levels of serotonin in the body, there may be underlying factors — such as genetics — making some people more prone to being negatively affected, Streicher said.

Of the large percentage of antidepressant takers who experience sexual side effects, there is a small percentage for whom those effects persist, or begin upon quitting the drug, for several years to decades after treatment — a condition known as post-SSRI sexual dysfunction, or PSSD. Despite its name, the condition, which has yet to be formally recognized, is often also paired with emotional, cognitive and physical dysfunction.

“We don’t really know what this (research) means in terms of predicting people who will develop PSSD,” Witt-Doerring said, but “it makes sense that it could decrease the chance that someone gets PSSD.”

The historical inability to predict antidepressant-related sexual dysfunction isn’t the result of dashed efforts, but of a general lack of scientific inquiry, Witt-Doerring said.

“I was just surprised to see that someone was even looking at that,” he added. “There’s obviously a really good public health incentive to do it, but that’s not always what really motivates people.”

The findings of the latest research “should encourage people to study this important side effect in more detail,” Jauhar said.

With the prevalence of antidepressant-related sexual dysfunction and patients who don’t respond well or at all to antidepressants, the latest science adds to a body of research that may advance the development of methods for predicting both effectiveness and harms of different drugs for the individual, Witt-Doerring said.

What to do about sexual dysfunction

To avoid antidepressant-related sexual dysfunction, many people opt for or switch to bupropion, a norepinephrine-dopamine reuptake inhibitor, or NDRI, Dr. Jonathan Alpert, the Dorothy and Marty Silverman Chair of the Department of Psychiatry and Behavioral Sciences at Montefiore Medical Center in New York City, told CNN in 2024. Instead of increasing serotonin, bupropion ups the amount of the neurotransmitter dopamine, which supports sexual desire and response.

If you’re already on an antidepressant causing sexual problems, work with your prescribing clinician to troubleshoot the issue and avoid potentially exacerbating it, Streicher said. They might wait and see if your body adjusts within a few months, but many people switch medications if they don’t want to wait or if side effects don’t alleviate, Alpert said.

Other times, to better manage or alleviate dysfunction, doctors may add another medication to a patient’s current routine. Medications for general sexual dysfunction, such as sildenafil or phosphodiesterase type 5 inhibitors, are sometimes prescribed to promote better blood flow and muscle relaxation in genital areas, counteracting the blood vessel constriction caused by high levels of serotonin, experts said.

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