In 2020, while under a strict lockdown, Rosie Tilli, a nurse in her twenties living and working in Melbourne, started to develop increasing anxiety and depression.

Upon visiting her doctor, she was promptly given a prescription for escitalopram, a frequently used medication belonging to a group called selective serotonin reuptake inhibitors (SSRIs). These drugs aim to alleviate depressive symptoms by increasing serotonin levels in the brain and are among the most commonly prescribed medications. In just 11 months of 2023, the NHS issued over 80 million prescriptions for antidepressants.

Tilli felt anxious about starting escitalopram, but after consulting with a psychiatrist, she decided to take the medication. Despite her expectations of feeling better, she instead experienced a decrease in libido and a complete loss of sexual sensation.

After conducting a rapid search on Google, she was informed about post-SSRI sexual dysfunction (PSSD), a condition that affects both men and women who have taken different SSRIs and may cause long-lasting sexual problems for years or even decades. Concerned by this information, she started gradually reducing her medication after four months, but saw no improvement.

“I told myself that I would be okay once I stopped taking the medication, but I was wrong,” she states. “Now, almost four years later, I have learned to put on a happy front, but internally, I am filled with emotional pain and distress. I am unable to feel any physical sexual response. There is no arousal even when touched. It’s as if the wiring of my sexual system has been damaged. My clitoris no longer has sensation, similar to my elbow, and there is no way to fix it.”

The initial cases of long-lasting sexual side-effects caused by SSRIs were reported in the 1990s, but the European Medicines Agency did not officially acknowledge PSSD as a condition until 2019. The PSSD Network, an organization for patients, has been established and its associated Reddit group has gained over 10,000 members globally.

David Healy, a psychiatrist and CEO of Data Based Medicine, a company focused on promoting safer medications, is worried that a large portion of patients being prescribed SSRIs are not suffering from severe depression. Instead, they are often teenagers and young adults with mild symptoms. He believes that these medications are being given out indiscriminately without much consideration. He acknowledges that those with a high risk of suicide do need treatment, but he argues that average family doctors are prescribing SSRIs to those who are only experiencing minor anxiety or depression. He also stresses the potential consequences, as these medications can lead to Persistent Sexual Side Effects (PSSD) and in turn, worsen suicidal tendencies.

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Tilli identifies herself as “completely broken” as a result of PSSD, and similar to others with the condition, she is afraid of being forever alone because it has rendered sexual intimacy and romantic relationships unattainable. Another person affected by PSSD described it as feeling like a “lobotomy”.

According to Tilli, there are other women experiencing PSSD who are considering undergoing artificial insemination in order to have a child because their condition has caused their relationships to end.

Currently, Healy and other scientists globally are striving to comprehend the reasons behind PSSD and if there is a potential to alleviate the symptoms.

Possible brain alterations

A definitive agreement has not been reached on the pervasiveness of persistent sexual dysfunction (PSSD). However, during the clinical launch of SSRIs, the initial labels stated that less than 5% of participants reported issues with sexual function. Yet, in certain undisclosed phase 1 trials, over half of the healthy volunteers experienced severe sexual problems, with some experiencing long-term effects even after treatment ended. A subsequent post-market research study revealed that 5% to 15% of patients developed sexual impairments after taking SSRIs, leading to concerns among doctors, such as Healy, about potentially underestimated prevalence rates.

The PSSD Network reports that SSRIs have been advertised to patients for over thirty years, but claims that mainstream psychiatry is disregarding the suffering experienced by these patients. According to the network, very few doctors have made an effort to understand the cause of this side effect and why certain individuals may be more susceptible to it.

In experiments on male rats, certain studies suggest that these medications may have harmful effects on the testicles. Researchers in São Paulo discovered that the antidepressant paroxetine can lead to changes in the testicles of lab animals, such as lower sperm production, even after the medication has been discontinued. However, a small group of scientists who have focused on this issue believe that the underlying reason for sexual side effects in individuals with PSSD is related to changes in the brain.

“I hypothesize that PSSD is predominantly a neurological dysfunction resulting from changes in brain function,” states Professor Roberto Melcangi from the University of Milan. He has been conducting research on this condition for the past three years, and has over ten years of expertise in studying sexual dysfunction induced by the medication finasteride, commonly used for treating male pattern baldness.

Melcangi and his colleagues have performed independent research on the effects of paroxetine on rodents. They are currently planning a similar study on a limited number of male patients with PSSD. Preliminary findings showed that the drug has the ability to modify certain steroid hormones, which play a crucial role in regulating brain function and sexual behavior. More trials have indicated that paroxetine may also disrupt the gut microbiome, which has a connection to the brain.

Antonei Csoka, a Howard University researcher focusing on ageing, has been investigating PSSD periodically since the early 2000s. He believes that SSRIs may cause changes in DNA modification due to their effect on serotonin receptors in the brain. These changes can impact the functioning of genes related to sexual function. The reason why this occurs in some individuals but not others is still unknown.

“Multiple researchers, including myself, have released research indicating that SSRI usage can alter epigenetics and human cells,” explains Csoka. “This suggests that, even after treatment has ceased, these cells or tissues may not fully return to their previous state. It’s similar to leaving an imprint. However, the specific nature of these epigenetic changes is still unknown. Therefore, we must focus our efforts on pinpointing the exact mechanisms at play.”

‘Medical gaslighting’

When Tilli initially started showing symptoms, her general practitioner labeled her as neurotic and denied that SSRIs could cause sexual dysfunction. The doctor then advised Tilli to do deep breathing exercises at home. However, things would become much worse for Tilli.

She shares that when she sought assistance from her community’s mental health facility, she was forcefully admitted for treatment and diagnosed with “delusional disorder” by a psychiatrist who also attempted to prescribe antipsychotics. This experience greatly damaged her confidence in seeking help for her mental well-being in the future.

Tilli and other individuals with PSSD believe they should have been more strongly informed about the potential adverse reactions of SSRIs before starting medication. Above all, they articulate a sense of being completely neglected by the medical field, with examples of what they refer to as “medical gaslighting,” where psychiatrists refuse to acknowledge the role of these drugs in causing harm.

Simultaneously, both the PSSD Network and researchers assert that there is a lack of funding to thoroughly comprehend the origin of these symptoms and continue the pursuit for potential remedies. A significant portion of Csoka’s PSSD research has had to rely on grants related to the aging process, while Melcangi’s work is partially funded by donations from PSSD patients.

According to Tilli, a member of the PSSD Network, it is the moral, ethical, and professional duty of the psychiatry profession and pharmaceutical companies to financially support research on the biological causes and treatments of PSSD. It is unfair and disrespectful to those who have suffered harm to expect them to fund their own PSSD research. This is especially concerning considering that many affected individuals are young adults who may not have the financial means to do so.

When the Observer asked for a response from GSK and Eli Lilly, the top producers of SSRIs, they did not mention any plans to support PSSD research in the future. GSK representatives stated that like any medication, SSRIs come with potential side effects, which are explicitly listed in the product information, and patients should only use them under the guidance of a healthcare provider.

The public relations team at Lilly released a statement that echoed the well-known SSRI fluoxetine, also referred to as Prozac: “Regulatory authorities, doctors, and patients worldwide still view fluoxetine as having a favorable balance of benefits and risks. Lilly continues to provide safety information about fluoxetine to regulatory bodies globally.”

Both Melcangi and Csoka suggest that potential treatments for PSSD exist, either by using existing medications for other purposes or utilizing new technologies to target the epigenome. Csoka is aware of reported instances where patients have had some success in regaining sexual function through taking certain nutraceuticals, undergoing low-level laser therapy, or using drugs like bupropion and vortioxetine to rebalance brain chemicals. Melcangi hopes to secure funding in the future to conduct a trial involving a drug called allopregnanolone, which he believes could help regulate abnormal brain function associated with PSSD.

However, there are numerous difficulties to address. PSSD may have multiple root causes that differ among individuals and between genders. Finding suitable treatments may be necessary for each patient, which poses a challenging and expensive task to comprehend the level of biological variability. Nevertheless, Melcangi remains hopeful that even with limited resources, there is still potential for finding a solution to aid those affected by this condition.

Finding a way to treat all the symptoms of PSSD may prove to be challenging, however, one crucial step would be to alleviate some of the negative effects, according to the speaker.

Having a shred of optimism is crucial for Tilli and her peers. She states, “Our group has sadly experienced numerous suicides.” Their primary objective is to increase understanding and secure funding for research, in order to discover potential treatments and prevent the hopelessness that drives individuals to take their own lives.

• In the UK and Ireland, individuals can reach out to Samaritans through the toll-free number 116 123 or via email at [email protected] or [email protected].
  In Australia, Lifeline can be contacted for crisis support at 13 11 14.
  In the US, the National Suicide Prevention Lifeline can be reached by calling or texting 988, chatting on 988lifeline.org, or texting HOME to 741741 to connect with a counselor during a crisis.
  For individuals in other countries, a list of international helplines can be found on befrienders.org.

Source: theguardian.com