During Melbourne’s strict lockdown in 2020, Rosie Tilli, a then 20-year-old nurse living and working in the city, began experiencing increasing anxiety and depression.
When she visited her doctor, she was quickly prescribed escitalopram, a commonly used drug in a class known as selective serotonin reuptake inhibitors (SSRIs). These medications attempt to treat depressive symptoms by increasing levels of the hormone serotonin in the brain and are among the most commonly prescribed medications. In the first eleven months of 2023 alone more than 80 million recipes for antidepressants are issued by the NHS.
Tilli was nervous about escitalopram, but, reassured by a psychiatrist, she started taking the tablets. But instead of experiencing relief, she soon noticed a worrying drop in her libido, combined with an inability to feel sexual sensations at all.
A quick Google search alerted her to a condition known as post-SSRI sexual dysfunction (PSSD), in which both men and women who have taken various SSRIs experience sexual problems that last for years or even decades. Alarmed, she began tapering off the medication after four months, but there was no change.
“I assured myself that everything would be fine once I stopped taking the medication completely, but it didn’t,” she says. ‘Now, almost four years later, I have learned to adopt a sunny disposition, but inside I am drenched in psychological sadness and fear. I cannot experience any physiological sexual response. No arousal even with physical touch. It’s as if the entire electrical wiring of the sexual system has been short-circuited. My clitoris now feels like my elbow, and I can’t do anything about it.”
While the first reports of persistent sexual side effects in response to SSRIs emerged in the early 1990s, PSSD was only recognized as a condition by the European Medicines Agency in 2019. A patient organization called the PSSD Network has launched and the connected Reddit community has amassed more than 10,000 members around the world.
Psychiatrist David Healey, founder and CEO of the company Data Based Medicine, which works to make medicine safer, is particularly concerned because the majority of patients treated with SSRIs are not the most severe cases of depression. Instead, he says, they tend to be individuals with milder symptoms, often teenagers and young adults. “Nowadays they are handed out without much thought,” he says. “It is absolutely true that people at high risk of suicide need treatment. But the average GP gives out SSRIs to people who are anxious or mildly depressed. They need to realize that if you cause PSSD, you will lead to suicide cases because people feel that they cannot live this way.
Tilli describes herself as ‘completely broken’ due to the effects of PSSD, and like many with the condition, she constantly fears being alone because it has made sexual intimacy and romantic relationships impossible. Another patient told the Observer that it feels like a ‘lobotomy’.
“I know other women with PSSD who are now talking about artificial insemination (to have a child) because all their relationships have failed because of the condition,” says Tilli.
Now Healy and other researchers around the world are trying to understand why PSSD occurs and whether it is possible to reverse the symptoms.
Possible brain changes
There is no precise consensus on the prevalence of PSSD, but when SSRIs were clinically launched this was stated on their original labels less than 5% of patients in clinical trials had reported sexual dysfunction. However, inside some unpublished phase 1 studies of the drugs, more than 50% of healthy volunteers developed serious sexual problems, which in some cases persisted after treatment was stopped. A post-market research found that between 5% and 15% of patients developed sexual impairment after taking SSRIs, and Healy and other doctors are now concerned that the prevalence could be greater than previously thought.
SSRIs have been marketed to patients for more than 30 years, but the PSSD Network says patients’ suffering is being ignored by mainstream psychiatry. Few doctors have tried to find out why this side effect occurs and why some people are particularly vulnerable.
Through testing in male rats, some studies have shown that these drugs can cause testicular toxicity. Last year, researchers from São Paulo discovered that the SSRI paroxetine can cause testicular changes in laboratory animals, including decreased sperm production, which persisted after the drug was stopped. However, the few scientists who have devoted themselves to this topic believe that the root cause of the genital numbness, lack of libido, and plethora of other sexual side effects that PSSD patients experience takes place in the brain.
“I believe that PSSD is primarily a neurological disorder related to altered brain functionality,” says Prof. Roberto Melcangi of the University of Milan, who has been researching the condition for the past three years and also for more than a decade spent studying sexual dysfunction caused by the drug finasteride, which is used for male pattern baldness.
Melcangi and his team have conducted their own research on paroxetine in rodents, which he now hopes to replicate in a small study of male PSSD patients. First results indicated that the drug could alter certain so-called steroid hormones, which act as important regulators of brain function, including sexual behavior. Further experiments have suggested that paroxetine might also affect the gut microbiome, which interacts with the brain.
Antonei Csoka, an aging researcher at Howard University who has been studying PSSD on and off since the early 2000s, suspects that SSRIs, as a side effect of targeting serotonin receptors in the brain, cause epigenetic changes, especially DNA modifications, which then affect the brain. activity of genes related to sexual function. Why this seems to happen in some unfortunate patients and not others remains a mystery.
“Several scientists, including myself, have published studies showing that an SSRI can alter epigenetics and human cells,” says Csoka. “If that happens, those cells or tissues may not immediately return to how they were once treatment stops. It’s like an imprint has been left behind. However, it is still not known exactly what these epigenetic changes are. So what we need to do is limit it – what happens?”
‘Medical gaslighting’
When Tilli first started experiencing symptoms, she was called neurotic by her GP, who insisted that SSRIs could not cause sexual dysfunction and sent her home to do deep breathing exercises. But much worse was to follow.
“When I sought help from the local mental health clinic, I was sectioned and involuntarily placed in psychiatric care because the psychiatrist said I had a ‘delusional disorder’ and tried to put me on antipsychotics,” she says. “It destroyed my confidence in ever seeking help for my mental health again.”
Tilli and other PSSD patients believe they should have received more warning about the potential side effects of SSRIs before starting the drugs. But most of all, they describe feeling completely left behind by the medical community through instances of what they call “medical gaslighting,” where psychiatrists refuse to acknowledge this source of drug-induced harm.
At the same time, the PSSD Network and researchers say funding to better understand the cause of these symptoms and advance the search for possible treatments remains virtually non-existent. Much of Csoka’s research on PSSD to date has had to be funded by grants in the aging field, while Melcangi’s work is partially funded by crowdfunding by PSSD patients themselves.
“Psychiatry and pharmaceutical companies have a moral, ethical and professional responsibility to fund research into the biological pathophysiology and treatments for PSSD,” says Tilli, who is part of the PSSD Network. “They are mocking injured patients by forcing us to self-fund our own PSSD research. In addition, many of the victims are teenagers and college students, working part-time for minimum wage or not at all.”
When the Observer approached leading SSRI manufacturers GSK and Eli Lilly for comment, but neither indicated they would fund PSSD research in the future. GSK representatives said: “Like all medicines, SSRIs have potential side effects. These are clearly stated in the prescribing information and patients should only use these medicines under the direction of a medical professional.”
Lilly’s PR team issued a similar statement regarding the SSRI fluoxetine, better known as Prozac: “Fluoxetine continues to be considered to have a positive benefit-risk profile by regulators, physicians and patients around the world. Lilly continues to submit safety data on fluoxetine to regulatory authorities around the world.”
Both Melcangi and Csoka believe that potential therapeutic solutions for PSSD exist, either by repurposing existing drugs or using emerging technologies to target the epigenome. Csoka is aware of case reports in which patients have managed to regain at least partial sexual function by taking drugs various nutraceuticalsusing low power laser therapyor medications that attempt to do so correct the chemical imbalances in the brain, such as bupropion and vortioxetine. In the coming years, Melcangi hopes to raise money for a trial of the drug allopregnanolone, which he believes could modulate the abnormal brain behavior behind cases of PSSD.
But there are many challenges. PSSD likely has many underlying causes, which vary both between individuals and between the sexes. Different patients may require different therapies, a level of biological variability that is both challenging and expensive to attempt to understand. But Melcangi is optimistic that even with limited resources, something can eventually be done to help people with the condition.
“It will be difficult to find a therapeutic approach… for all the effects of PSSD, but an important step would be to counteract at least some of the side effects,” he says.
For Tilli and others, having even a glimmer of hope is vital. “Our community has had a lot of suicides,” she said. “Our main goal is to raise awareness so we can secure funding for research to pave a path to hopeful treatments and prevent the despair that leads many to end their lives.”