The European Medicines Agency has just concluded a review into sexual dysfunction after the discontinuation of SSRIs and SNRIs. Before we discuss their findings, it’s worth looking back over the events of the past year.
In 2018, we put together a petition requesting changes to SSRI and SNRI product labels to warn about post-SSRI sexual dysfunction (PSSD) and persistent genital arousal disorder (PGAD). It was endorsed by 22 signatories, the majority of whom were peer-reviewed authors of the medical literature on PSSD and PGAD.
In addition to being a petition, it was a comprehensive review of the medical literature on these conditions to date, and was published in the International Journal of Risk and Safety in Medicine.
In May 2018, we submitted the petition to the European Medicines Agency (EMA), the Food and Drug Administration (FDA), and Britain’s Medicines and Healthcare products Regulatory Agency (MHRA).
On July 4, 2018, EMA informed us that the petition had been forwarded to their Pharmacovigilance Risk Assessment Committee (PRAC) for further investigation. We received a further response on September 14, to say they had begun a review of sexual dysfunctions after discontinuation of SSRIs and SNRIs.
One of the reasons that regulators may have been so slow to act in the case of PSSD and PGAD, despite significant numbers of reports to them, is because those reports are usually anonymous. This means there is no opportunity to follow them up and they can easily be dismissed as hearsay.
In October 2018, we had an idea that might help. We contacted over 300 people who had reported PSSD or PGAD to RxISK, asking if they would be willing to complete a report for EMA including details of their case, their name and email address, and indicating a willingness to be contacted by the regulator if necessary.
We also asked if it might be possible to get a supporting letter from a healthcare professional, as we thought this might make a difference in terms of the reports being taken seriously. Healthcare professionals wouldn’t necessarily have to say that the antidepressant had caused the problem, only that there was no other competing explanation. We were happy to accept either brand new letters written specifically for the review, or existing documentation.
Due to the sensitive nature of the conditions and concerns over confidentiality, we knew that most PSSD and PGAD sufferers would be reluctant to participate. We also knew that very few would be willing to approach a healthcare professional for a supporting letter.
From the many that we contacted, a small number expressed an interest in getting involved, so we put the proposal to EMA. They accepted our offer and told us what information they wanted.
Due to a tight timescale set by EMA, it turned out to be a very challenging project, but we managed to submit a total of 82 named reports, of which 32 contained supporting documentation from healthcare professionals.
EMA concludes its review
On May 31, 2019, we received the following message from EMA:
Dear Professor Healy,
We are writing to you to inform you that the review by EMA’s safety committee PRAC into sexual dysfunction with SSRIs and SNRIs has now concluded. We would like to take this opportunity to thank you and the patients involved for your important contribution in supporting EMA in its role of supervising medicines’ safety in Europe. Patient reports such as the ones you submitted are essential to gain a better insight into a medicine’s safety profile and were a valuable contribution to this review.
On Thursday 16 May, PRAC concluded that sexual dysfunction, which is known to occur with treatment with SSRIs and SNRIs and usually resolves after treatment has stopped, can be long-lasting in some patients, even after treatment withdrawal. In addition to the patient reports provided, PRAC also assessed data from the published literature, clinical and non-clinical studies, as well as data gathered by the marketing authorisation holder in its safety databases and reports collected through the Eudravigilance database.
Based on this data it is currently not known how long these symptoms can persist, and the issue will continue to be closely monitored.
The outcome of the review will be made public on EMA’s website on 10 June 2019:
We hope you find this information useful and we would like to take this opportunity to thank you for your important contribution to public health.
Stakeholders & Communication
European Medicines Agency
Another member of the wider RxISK community had this reply:
Thank you for your message to EMA about epitt 19277.
The review by EMA’s safety committee PRAC into this signal (sexual dysfunction with SSRIs and SNRIs) has now concluded. The PRAC concluded that sexual dysfunction, which is known to occur with treatment with SSRIs and SNRIs and usually resolves after treatment has stopped, can be long-lasting in some patients, even after treatment withdrawal.
The PRAC assessed data from patient reports, the published literature, clinical and non-clinical studies, as well as data gathered by the marketing authorisation holder in its safety databases and reports collected through the Eudravigilance database. Based on this data it is currently not known how long these symptoms can persist, and the issue will continue to be closely monitored.
The PRAC recommended that the product information of all SSRIs and SNRIs be updated to make reference to reports of long-lasting sexual dysfunction where the symptoms have continued even after patients stopped using the medicines. At present, no such evidence could be found for clomipramine and vortioxetine and the PRAC therefore did not recommend updates of the product information for these medicines.
The outcome of the review will be made public on EMA’s website shortly:
I hope this information is helpful.
Stakeholders and Communication Division
A good result?
EMA’s public statement is now available on the above link.
Many would argue that it doesn’t go far enough. It’s a long way from the warnings we requested in the petition. Nevertheless, it’s a step forward. It means that for the first time, patients who are newly prescribed an SSRI or SNRI will, if they read the product information, be warned about the risk of long-term sexual dysfunction even after discontinuation of the drug.
While there was no warning for the many people who’ve already had their lives altered by PSSD and PGAD, one of the concerns many of those who have been affected have had is the impact on others – they don’t want this to happen to anyone but especially children, teenagers, and young adults.
We would like to thank everyone who has been involved in this effort over the last year including those who agreed to be signatories on the petition, everyone who completed a named report for EMA, everyone who attempted to get a supporting letter from a healthcare professional, and those healthcare professionals that agreed to write one.
Following the conclusion of EMA’s review, we are not expecting a separate response from MHRA, as decisions over drug labelling are likely to be taken centrally at European level.
However, we await FDA’s response. At the moment, the petition is still lodged within FDA’s official Citizen Petition process. The last communication we received was an interim response dated November 6, 2018, confirming that no decision had yet been made and that their review into the issues raised was still ongoing.
They are also still reviewing our petition as regards retinoids and post-retinoid sexual dysfunction.
In a further development, we were contacted by Health Canada in January 2019. They had become aware of our petition and our 2018 paper on 300 cases of enduring sexual dysfunction, and were seeking more information. With permission, we supplied Health Canada with the named reports and supporting documentation that we had submitted to EMA. They acknowledged receipt but have yet to respond.
The EMA Image above suggests politics (chess) and religion (a sacrament being held over a bowl), both of which apply to the regulation of medicines. This image appeared at a time when the Netherlands was bidding to rehouse a Brexiting EMA. Who knows what the politics have been behind the latest updates on one of our most cherished sacraments.