Your donations are needed to fund scientific research into post-SSRI sexual dysfunction (PSSD) and other enduring sexual dysfunctions. The aim is to better understand the biology of these conditions and hopefully find treatments.
£45,548 raised of £50,000 goal
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The conditions
Post-SSRI sexual dysfunction (PSSD) is a condition in which sexual side effects don’t resolve after stopping certain types of antidepressants (inc. SSRIs, SNRIs and some tricyclics). In some cases, the sexual side effects only emerge upon stopping the antidepressant.
The condition affects men and women of all ages and causes genital numbness, pleasureless orgasm, loss of sex drive, impotence and other difficulties. It can start after only a few days of taking an antidepressant and in some cases persists for decades. There is currently no treatment.
It can lead to relationship and family breakup, job loss, and suicide.
There are other related conditions:
- Persistent genital arousal disorder (PGAD) which can be triggered by stopping SSRIs.
- Post-finasteride syndrome (PFS) caused by finasteride, a medication used to reverse hair loss in young men.
- Post-retinoid sexual dysfunction (PRSD) caused by isotretinoin, a medication used in the treatment of acne.
The fund
Our research fund was launched on 21 June 2022 with the aim of facilitating scientific research into PSSD and other enduring sexual dysfunctions. Donations are made to Centre for Data Based Medicine, a registered charity in England and Wales.
All major cards are accepted, or you can pay using a PayPal account. If you have any difficulty donating, please contact us.
The total is updated manually by our team, so don’t worry if your donation doesn’t appear immediately.
Please note that our research fund is not affiliated with any other group. All projects currently supported by our fund are described below. We are not necessarily committed to these – we keep our options under constant review.
Research
Updated 26 May 2025.
RxISK has been involved in pursuing treatments for PSSD prior to establishing the research fund.
In 2015, having published on the sometimes miraculous benefits of relatively high intramuscular doses of ketamine for severe melancholia, the RxISK team recruited 3 subjects with confirmed PSSD, who were free of all treatment, and 3 subjects with protracted withdrawal from SSRIs, one of whom was on a low dose of paroxetine she could not stop, to be given an intramuscular injection of 50 mg of ketamine.
None of the 3 PSSD subjects showed any benefit. None of the 3 withdrawal patients showed any benefit – if anything, they were temporarily worse.
In 2017, based on reports from San Diego that intraspinal injections of 1 mg dexamethasone produced a temporary benefit in PSSD, we gave 6 PSSD volunteers a daily course of dexamethasone 5 mg orally for a week (equivalent to 40/50 mg cortisone). One volunteer had a temporary benefit.
In 2021, Dr Healy supported the treatment of 2 patients who were non SSRI responders with psilocybin. Both did much better on psilocybin. Neither however had PSSD or protracted withdrawal. At present there are no grounds to think psilocybin would help these states.
Pirenzepine and oxybutynin
The pharmacuetical company, WinSanTor, is trying to find a way to get pirenzepine on the market as a treatment for peripheral neuropathy in diabetes. One of us (DH) had a meeting with WinSanTor in mid-2022 and made them aware of PSSD. Although their website now mentions sexual dysfunction including PSSD, we are currently unaware of any work being done by WinSanTor involving PSSD.
We have had two volunteers try oxybutynin, a closely related drug, but it had no obvious benefit. This casts doubt on whether WinSanTor’s pirenzepine would be of benefit in PSSD. We have been trying to get some German colleagues to try pirenzepine which is available there, but we’ve been unable to find any volunteers.
Von Frey filaments
As previously noted, we have had several volunteers tested with von Frey filaments. This test does seem to pick up genital numbness. No one knows for certain what the normal sensitivity should be for the genital area, but with a condition like PSSD, testing before and after a potential treatment for PSSD allows people to act as their own control. The equipment is not expensive, but it is a two-person job.
Neuroplasticity/hyperbaric oxygen therapy
Over the last 7 years since it started, we have had lots of proposals for ways to cure PSSD, aimed at claiming the RxISK Prize. We have a panel of volunteers with genuine PSSD who are willing to test safe options, and several have been tested but nothing has worked.
A few months ago, we had a very different proposal that combines physical and psychotherapy elements from a group of enthusiasts for the approach. It likely could be helpful for many problems, but we will have to see if it helps PSSD.
We originally had 4 volunteers, all of whom had von Frey filament testing of their genitals prior to commencing the protocol and showed abnormalities. The plan was to test again after treatment finishes.
When fully informed about the protocol two decided not to participate, one commenced treatment but has dropped out as it was not suiting, and another is about to start.
We will post more information when we have it.
Transcranial photobiomodulation therapy
Over a decade ago, Marcel Waldinger showed that low-powered laser irradiation could produce a 20% reduction in genital numbing. Like laser, photobiomodulation is a light therapy – in this case less focussed and infrared. The claim is it kick starts mitochondria that have lost the will to live (produce energy), and this can lead to nerve regeneration.
We have previously tracked the use of transcranial photobiomodulation therapy in two PSSD sufferers, following literature claims it would likely help and some claims from sufferers that it had helped them.
There is published literature describing its use in antidepressant-induced sexual dysfunction, but to our knowledge this was the first time it has been tried in PSSD patients. Unfortunately, in our volunteers there were no noticeable benefits.
Milan
Nothing has changed in respect of our discontinued support for this project. To recap –
A little over 2 years ago, RxISK began supporting Professor Luisa Guerrini in her research looking at the effects of SSRI drugs on p63 regulatory proteins. Both thalidomide and SSRIs it appears act on p63, and this may explain how both can cause birth defects.
The research has drawn our attention to and may help explain some anti-cancer and antiviral effects of SSRIs, which they also share with thalidomide and related drugs.
While there seemed to be very clear effects of SSRIs on p63 proteins, the work had not got to the point of being publishable when unfortunately Luisa’s main research assistant left. Luisa has not been able to replace her. This may have been because the pay we could offer was not attractive enough, or it may be due to other reasons. Not being based in Milan, it’s difficult to know.
This project, which appeared to be breaking new ground has therefore come to a stop for the moment. Without a clear path forward we have opted not to fund it further.
Corneal confocal microscopy
As previously reported, we had been exploring whether corneal confocal microscopy (CCM) testing might be a way to establish a diagnosis of PSSD. This work has been linked to Professor Mitra Tavakoli from the University of Exeter, who is an acknowledged expert on CCM. We organized for and sponsored 12 volunteers to visit her lab and be tested for peripheral neuropathy and by CCM.
Prof Tavakoli tested our volunteers while also running the same protocol in a large study under the auspices of the pharmaceutical company Sanofi. She has provided the results of peripheral neuropathy tests and some CCM data. However, she has not provided an analysis of dendritic cells, despite being implored to do so.
Efforts by ourselves and those who participated have been unable to resolve the situation. This has been extremely frustrating, and we intend to pursue this further with the relevant ethics committee and Sanofi. We are disappointed in Prof Tavakoli and the University of Exeter.
Anesthetics
Several people have contacted RxISK to report benefits from propofol, a drug used to induce anesthesia. The benefits have been real but short-lived, perhaps because the anesthetic was brief.
Recently, we had someone who had propofol and another anesthetic, sevoflurane, and had substantial improvements that lasted two months. Googling propofol and anesthetics, you can find reports that some people who do not have PSSD can have significant energizing and sexual effects for periods of time afterwards.
A recent Nature paper pointed to new effects of propofol on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that might explain these benefits. We have written to the authors but had no response – even hanging the Prize bait in front of them.
If you want to contact them, the corresponding authors are:
H. Peter Larsson; peter.larsson@liu.se
Crina M. Nimigean; crn2002@med.cornell.edu
RxISK Prize
For 7 years now we have a RxISK Prize in place. One hope behind this was to stimulate researchers to see if what they were working on might help this condition few of them will have heard of.
A second benefit is that if any of you hear of some promising cure, rather than starting off by taking risks on something that might or might not be helpful, the Prize offers you a chance to approach researchers and say a number of people with PSSD wonder if your recent research might offer a cure for PSSD – if you think it might, have you considered contacting RxISK to see what you might need to do to claim the $100K Prize? If no-one even attempts to make contact about the Prize, you can draw your own conclusions.
Money disbursed
- Von Frey Filaments £394.25 on 28 January 2024
- CCM study £1,100 on 19 October 2023
- £15 transaction fee on 12 July 2023
- £9,642.36 to Dr. Luisa Guerrini on 12 July 2023
- Open access fee of £1,289 on 29 June 2023
- Transaction fee of £5 on 27 July 2022
- £13,925.15 to Dr. Luisa Guerrini on 26 July 2022