The dangers of anti depressants

[sammyboyfor]

https://www.theguardian.com/society/...quences-libido

‘It feels like we’ve been lobotomised’: the possible sexual consequences of SSRIs
David Cox
11–13 minutes

During Melbourne’s strict lockdown of 2020, Rosie Tilli, a then 20-year-old nurse living and working in the city, began to experience growing anxiety and depression.

Visiting her GP, she was quickly prescribed escitalopram, a commonly used drug from a class known as selective serotonin reuptake inhibitors (SSRIs). These medicines attempt to treat depressive symptoms by boosting the levels of the hormone serotonin in the brain and rank among the most widely prescribed drugs. In the first 11 months of 2023 alone, more than 80m prescriptions for antidepressants were issued by the NHS.

Tilli was nervous about escitalopram but, reassured by a psychiatrist, she began taking the tablets. However, rather than experiencing relief, she soon noticed a worrying drop in her libido combined with an inability to feel any sexual sensations at all.

A quick Google search alerted her to a condition known as post-SSRI sexual dysfunction (PSSD), where both men and women who have taken various SSRIs have been left with sexual problems, persisting for years or even decades. Alarmed, she began tapering off the medication after four months, but there was no change.

“I reassured myself that I would be fine as soon as I fully ceased the medication, but I wasn’t,” she says. “Now nearly four years on, I’ve learned to put on a sunny disposition, but internally I am riddled with psychological grief and anguish. I can’t experience any physiological sexual response. No arousal even when physically touched. It’s as if the entire electrical hardwiring of the sexual system has been short circuited. My clitoris feels like my elbow now, and there’s nothing I can do to reverse it.”

While the first reports of persistent sexual side-effects in response to SSRIs began emerging in the early 1990s, PSSD as a condition was not recognised by the European Medicines Agency until 2019. A patient organisation called the PSSD Network has been launched, and its affiliated Reddit community has amassed more than 10,000 members around the world.

Psychiatrist David Healy, founder and CEO of the company Data Based Medicine, which is dedicated to making medicines safer, is particularly concerned because the majority of patients who are 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. “They’re being handed out without much thought these days,” he says. “Now absolutely, people who are at high risk of suicide do need treatment. But the average family doctor is handing SSRIs out to people who are anxious or mildly depressed. They need to realise that if you cause PSSD, you’re going to lead to suicide cases because people feel they can’t live this way.”
Rosie Tilli sitting under a tree
Rosie Tilli: ‘Pharmaceutical companies and psychiatrists have a moral, ethical and professional responsibility to fund research.’ Photograph: Arsineh Houspian

Tilli describes herself as “completely broken” due to the effects of PSSD, and like many with the condition she fears being perpetually alone because it has made sexual intimacy and romantic relationships impossible. Another sufferer told the Observer that it feels akin to having been “lobotomised”.

“I know of other women with PSSD who are now speaking of getting artificial insemination [to have a child] because all of their relationships have failed due to the condition,” says Tilli.

Now Healy and other researchers around the world are working to try to understand why PSSD occurs, and whether it may be possible to reverse the symptoms.
Possible brain alterations

There is no precise consensus regarding the prevalence of PSSD, but when SSRIs were launched clinically, their initial labels stated that less than 5% of patients in clinical trials had reported sexual dysfunction. However, in some unpublished phase 1 trials of the drugs, more than 50% of healthy volunteers developed severe sexual problems, which in some cases persisted after treatment stopped. One post-market research study found that between 5% and 15% of patients developed sexual impairments 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 three decades, yet the PSSD Network says patients’ suffering is being ignored by mainstream psychiatry. Few doctors, it says, have attempted to delve into why this side-effect occurs, and why some people are especially vulnerable.

Through testing in male rats, some studies have indicated that these drugs may cause toxicity to the testicles. Last year researchers from São Paulo found that the SSRI paroxetine can cause testicular changes in lab animals, including impaired sperm production, which persisted after the drug was stopped. However, the few scientists who have dedicated 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 sufferers experience happens in the brain.

“I believe that PSSD is primarily a neurological disorder relating to altered brain functionality,” says Prof Roberto Melcangi of the University of Milan, who has been researching the condition for the last three years and has also spent more than a decade studying sexual dysfunction caused by the drug finasteride, which is taken for male pattern baldness.

Melcangi and his team have conducted their own research on paroxetine in rodents, which he is now hoping to replicate in a small study of male PSSD patients. Initial results indicated that the drug could alter certain so-called steroid hormones, which act as important regulators of brain function, including sexual behaviour. Further experiments have suggested that paroxetine might also impair the gut microbiome, which interacts with the brain.

Antonei Csoka, a researcher on ageing at Howard University, who has been studying PSSD intermittently since the early 2000s, suspects that as a side-effect of targeting serotonin receptors in the brain, SSRIs drive epigenetic changes, particular DNA modifications, which then affect the activity of genes relating to sexual function. Why this seems to happen in some unlucky patients and not others remains a mystery.

“Various scientists, including myself, have published studies showing that an SSRI can change epigenetics and human cells,” says Csoka. “If that’s happening, then those cells or tissues may not immediately revert back to how they were once treatment stops. It’s as though an imprint has been left there. However, it’s still not known precisely what these epigenetic changes are. So what we need to do is narrow it down – what is happening?”

‘Medical gaslighting’

When Tilli first began 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 far worse would follow.

“When I reached out for help with my local mental health service, I was sectioned and placed involuntarily into psychiatric care as the psychiatrist said I had ‘delusional disorder’, and tried to put me on antipsychotics,” she says. “It shattered my trust in ever seeking help for my mental health again.”

Tilli and other PSSD patients feel they should have been given greater warning of the potential side-effects of SSRIs before commencing the drugs. However, most of all they describe feeling completely abandoned to their fate by the medical community, through cases of what they call “medical gaslighting”, with psychiatrists refusing to acknowledge this source of drug-induced harm.

At the same time, the PSSD Network and researchers say that funding to better understand the cause of these symptoms and further the search for potential treatments remains virtually nonexistent. Much of Csoka’s research into PSSD so far has needed to be covered by grants relating to ageing, while Melcangi’s work is partly crowdfunded by PSSD patients themselves.

“The psychiatry profession 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 harmed patients by forcing us to self-fund our own PSSD research. On top of that, many sufferers are teenagers and university students, who either work part-time for minimum wage or not at all.”

When the Observer approached leading SSRI manufacturers GSK and Eli Lilly for comment, neither indicated that they would consider funding PSSD research in future. GSK representatives said: “As with all medicines, SSRIs have potential side-effects. These are clearly stated in the prescribing information and patients should only take these medicines under the direction of a medical professional.”

The Lilly public affairs team issued a similar statement regarding the SSRI fluoxetine, commonly known as Prozac: “Fluoxetine continues to be considered to have a positive benefit-risk profile by regulatory authorities, physicians and patients around the world. Lilly continues to submit fluoxetine safety data to regulatory authorities around the world.”

Both Melcangi and Csoka believe that potential therapeutic solutions for PSSD are out there, either through repurposing existing drugs or using emerging technologies to target the epigenome. Csoka is aware of case reports where patients have managed to regain at least partial sexual function either through taking various nutraceuticals, using low-power laser therapy, or drugs that attempt to readjust the chemical imbalances in the brain, such as bupropion and vortioxetine. In the coming years, Melcangi hopes to raise funds to conduct a trial using a drug called allopregnanolone, which he believes could modulate the abnormal brain behaviour behind cases of PSSD.

But there are many challenges. PSSD is likely to have many underlying causes, which vary both between individuals and between the sexes. Different therapies may be required for different patients, a level of biological variability that is both challenging and costly to try to understand. But Melcangi is optimistic that even with limited resources, something might ultimately 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 at least counteract some of the side-effects,” he says.

For Tilli and others, having even a glimmer of hope is vital. “Our community has had many suicides,” she says. “Our main goal is to raise awareness so that we can get funding for research to pave a path towards hopeful treatments and prevent the despair that leads many to end their lives.”