This post gives the text of an article that has just been published online in the Journal of the Royal Society of Medicine – see Here.
Another version of the material is in video form – Antidepressants and Sex: a Strange Story.
Background
In June 2019, in response to a petition, the European Medicines Agency (EMA) asked pharmaceutical companies to warn that sexual dysfunction can endure after antidepressant treatment stops.
History
The effect of antidepressants on sex was first noted in 1960 by Frank Ayd, a psychiatrist and the discoverer of amitriptyline, who linked amitriptyline treatment to a sexual dysfunction distinct from the loss of libido that the melancholic states it was being used to treat can cause.
In the 1970s, George Beaumont, working for Geigy Pharmaceuticals, had the job of finding a niche for clomipramine, now regarded as the most potent antidepressant, but then another molecule in a crowded field. He placed articles in newspapers featuring a minor celebrity, thrilled that her boyfriend’s premature ejaculation problem could be managed by 10 mg of clomipramine taken 30 minutes before intercourse – the standard antidepressant dose is 150 mg.
Beaumont also established clomipramine as the premier drug treatment for Obsessive-Compulsive Disorder (OCD). As clomipramine use encroached on behaviour therapy for OCD in the 1980s, in public lectures, Isaac Marks, the leading proponent of behaviour therapy drew attention to the persistent orgasms a patient of his, a nun, experienced after withdrawal from clomipramine. This may be a first linkage of what is now called persistent genital arousal disorder (PGAD) to withdrawal from a serotonin reuptake inhibitor.
In 2001, Sandra Leiblum formally described Persistent Genital Arousal Disorder. Although a psychotherapist, she was convinced the persistent arousal 4 of her patients had was organic rather than psychological. PGAD primarily affects women and is now linked to hormonal changes around the menopause as well as discontinuation from serotonin reuptake inhibitor drugs – which includes many antibiotics, antihistamines, and analgesics in addition to antidepressants. The women affected have turned to perineal nerve ablation, clitoridectomy, ECT and other drastic remedies, without benefit.
The Selective Serotonin Reuptake Inhibitor (SSRI) group of antidepressants are derived from clomipramine and were launched in the years around 1990. SSRIs are relatively ineffective for melancholia, a rare disorder compared to the nervous problems for which doctors around 1990 were giving benzodiazepines. The marketing need for the SSRIs was to transform cases of Valium, rather than cases of clomipramine, into cases of Prozac.
Doctors began to hear they could be sued for prescribing benzodiazepines which cause dependence. The real need they were told was to treat the underlying depression, with antidepressants, which did not cause dependence, rather than treat the superficial anxiety with dependence producing drugs.
In the 1980s, prior to marketing, healthy volunteers in phase 1 studies of SSRIs, however, had become dependent on SSRIs and were left anxious and depressed afterwards. Within 3 years of paroxetine being on the market, there were more reports in Britain about dependence on it than there had been in 20 years from all benzodiazepines combined.
The initial labels for all SSRIs when these drugs were launched clinically stated that less than 5% of patients in clinical trials reported sexual dysfunction. But in some unpublished phase 1 trials, over 50% of healthy volunteers had severe sexual dysfunction that in some cases lasted after treatment stopped.
Over 50% becomes less than 5% primarily because in clinical trials investigators have innumerable boxes to tick, almost entirely devoted to the question of whether the drug works, and minimal space and time to record adverse events. They may not, therefore, record a problem, in particular one that can be passed off as a feature of the illness.
Phase 1 trials also offer companies a clear view of a drug’s adverse effects making it possible to design trials that will not find the problem. In the case of study 29060/136, comparing paroxetine to clomipramine in Obsessive-Compulsive Disorder, the trial originally had a Limited Symptom Checklist with 14 questions of which 8 centred on sexual function. But investigators, like me, were told not to ask these questions.
The resulting 5% clinical trial figure trumped later evidence from surveys that gave rates of over 50% consistent with the unpublished phase 1 studies. The 5% figure even trumped a marketing of dapoxetine, an SSRI, for premature ejaculation, which depends on the drug impacting on the sexual functioning of close to 100% of the men who take it.
Clinicians were advised to tell patients taking SSRIs that any sexual problems would remit once treatment stopped and that they could even take a break from treatment for a romantic weekend.
The first report to British regulators of a patient with post treatment genital arousal disorder dates to 1987. The first report of what is now called Post-SSRI Sexual Dysfunction (PSSD) was filed in 1991. It is likely that no doctors are aware of this.
I saw my first patient with what was later called PSSD in 2000; a 35-year old lady who told me that 3 months after stopping treatment she could rub a hard-bristled brush across her genitals and feel nothing.
In 2006 Bahrick, and Csoka formally described PSSD. They were helped in this by a lot of sufferers, especially Kevin Bennett who played a key role in being willing to have his name linked to the condition and to be cross-examined at academic meetings. Kevin and other sufferers could reliably date their condition to the early 1990s, so that by 2006 their problems had persisted for over a decade.
In an effort to find a cure, hundreds of women and men in internet forums have since exchanged information about the effects of drugs acting on serotonin or dopamine systems, phosphodiesterase inhibitors, herbs, metals and operative procedures, all of which had some rationale, but many of which were dangerous, and none of which work. Some forum participants appear to have committed suicide. I have been contacted by Dignitas, the assisted dying centre in Zurich, asking about the nature of this problem because of a number of young people have referred themselves there.
The core features of the condition are genital numbing, loss or muting of orgasm and loss of libido. But many are just as concerned by additional features like emotional numbing or derealisation. Both sexes, all ages and every ethnic group can be affected. The problem may begin after only a few doses and leave someone affected for life. Or a relatively mild dysfunction can worsen dramatically when the person stops treatment.
In 2011 an almost identical problem, post finasteride syndrome (PFS), was reported. Finasteride has been marketed since 1997 to young men with thinning hair.
In 2014, a similar post-retinoid syndrome (PRSD) was described following isotretinoin (Accutane). These problems have also been happening for decades previously. In 2006 a man suffering sexual dysfunction following isotretinoin killed the doctor who prescribed it to him.
With colleagues, in 2018, I reported on 300 cases of enduring sexual dysfunction following antidepressants, finasteride or isotretinoin. We decided to petition EMA to have PSSD recognized on drug labels, hoping recognition might lead to research and treatment.
Another reason was because, in addition to the direct treatment harms, many patients are harmed by the response of their doctors. They are ridiculed for thinking a drug could cause a problem after it leaves the body. They are referred for therapy of childhood issues, or told, if they consult Google, they will have problems for ever, or they may be offered antidepressants.
Why would regulators who have been sitting on thousands of reports from doctors for years, act in response to us? Reports from doctors to regulators are anonymised. This transforms them into hearsay. Unless a patient and doctor can be cross-examined it is not possible to establish causality. Aware of this, with the agreement of patients, we sent EMA 84 named patient reports and contact emails and 32 letters from doctors to confirm the patient’s identity, their treatment with an SSRI and the lack of a competing explanation for their difficulties. EMA were told we were offering them the possibility to cross-examine patients or their doctors to establish causality.
In contrast to regulators, companies are obliged to follow us up if we report. They seek access our medical records in order to find ways to explain the problem away. When their drug is the only way to explain the problem, companies include it on their label under “other reports”, which for doctors for the most read as indicating that companies even let us know about reports from “Flat-Earthers”. PSSD has not appeared there because companies have a get out – the patients were depressed.
In June 2019, EMA agreed to ask companies to note a problem described nearly 30 years previously.
Ways Forward
Sixty years ago, it rarely took more than a few years between the first reporting of problems such as sexual dysfunction on amitriptyline, to wider acceptance. PSSD, PFS and PRSD now join a growing group of significant adverse events that have taken over 3 decades from the point of first description to a linkage to treatment.
Key to reversing the increasing delay in recognising common effects drugs can cause is a willingness on the part of patients and doctors to put their names to reports and be cross-examined. This – not clinical trials – is how to establish drug X causes effect Y.
In May 2019, BMJ featured a study on Declining Sex in Britain that fingered depression as a leading cause of this decline. Neither the BMJ nor media coverage mentioned that neither the nervous problems for which benzodiazepines were given, nor the benzodiazepines caused sexual dysfunction. Antidepressants are more likely than the nervous problems for which they are now given to wipe out our interest in or ability to make love.
Meanwhile 10% of people of sexually active years in developed countries are on antidepressants chronically. Nearly 20% of the population, therefore, may not be able to make love the way they want. In some deprived areas, the figure may be much higher. Some likely comfort themselves with the thought that once they stop treatment, they will get back to normal, when in fact they may be even less able to function.
There is a great need to recognise these treatment-related enduring sexual dysfunctions and pinpoint how they arise and might be treated.
John says
Thank you for the continuous recognition of pssd. Speaking of I have pssd and have had it for about 3 years now. And have recently experienced nerve pain in the testicles that occurs when stressed or nervous. Is recognized when it comes to pssd ? Will typical prescription nerve pain medication help the issue ?
Thank you
Spruce says
I have PSSD and have needling type nerve pains in my genitals and testicles, in a sporadic, but almost daily basis. Although the pain is usually quite mild, occasionally i would describe it as moderately painful.
John says
Thank you for the reply spruce,
regarding the pain have you tried nerve medications for relief ? Also is nerve pain not common when it comes to pssd ? Symptoms of nerve pain do not show up On any pssd symptom page.
Spruce says
Hi John. No i have never tried any medication to treat the nerve pains.
The nerve pains feel like an indication that my body is trying to heal itself from the PSSD, and reverse whatever changes the PSSD has caused, so i am reluctant to try and interfere with this process in any way by treating it with medication.
The needling nerve pains seem to be getting a bit stronger and more frequent as time goes by, and they seem to be spreading to other areas too, but in a slightly different form, where once they were isolated to my penis and testicle area.
In the last few months they have been happening also in my right quad on my right leg, on the left side of my neck, and also the upper left side of my back. The nerve pains in the areas i just mentioned feel more like a tingling sensation that passes in a wave like procession over an area of skin, and aren’t really painful. They feel slightly different from the nerve pains i get in my genital area which feel like needling type nerve pains that go in an almost snake or worm like fashion, and can be mildly to moderately painful.
I have also been getting some quite sharp occasional nerve pains in the area just above my genitals up towards my belly button. These also have only seemed to have started in the last few months.
I strongly believe these nerve pains/ tingling are related to the PSSD and not something else.
I have heard of others with PSSD having nerve pains too.
John says
Thanks again spruce, fertility is also one thing I can’t find an answer too when it comes to pssd, have you tried starting a family with pssd or can you ? With all of this pain in the testicles, fertility is one thing I’m also concerned about
Ken says
I also have had bouts of nerve pain in various areas of my body since discontinuation of the SSRI I was on back in 2012. I thought I was the only one going through this. It has been hard to convince doctors all of my symptoms were caused by the SSRI I was on.
tim says
Thank you for this brilliant start to a new decade.
Delighted to see such an important publication in the Journal of The Royal Society of Medicine.
I have read and re-read this afternoon.
“There is a great need to recognise these treatment-related enduring sexual dysfunctions and pinpoint how they arise and might be treated”.
Yes indeed.
Should be compulsory bedtime-reading for all prescribers.
Spruce says
I have just today found out that another person with PSSD has commited suicide. She died on 26/10/2019, at the age of 17. She went by the name of Potions on the facebook group, and marrybanana on the PSSD forum, but her real name was Margaret.
I chatted to her online on the PSSD facebook group for about 2 years. She would often talk about suicide, and how her doctors refused to believe her sexual problems had been caused by the SSRI she had been given, stating her psychiatrist actually shouted at her “in all my years of being a psychiatrist i have never heard of anything like it”.
Another member of the PSSD facebook group has today told me she is going to take her life soon too, as she feels completely hopeless about her recovery, her doctors wont believe her, and even her own brothers have been taunting her about her sexual dysfunction. I am quite close to this person and she is one of only a few people who understands what has happened to me.
I am having thoughts of suicide again myself. I really dont know how much longer i can endure all this. In November of this year it will be 13 years i will have had PSSD with only small improvements to show.
None of my past doctors who prescribed me the Citalopram want to know. I have told my ex psychiatrist repeatedly about the damage that has been done to me, but he doesn’t want to know. I wrote a letter to my ex GP describing what has happened to me but he didn’t bother to reply to my letter.
I am really struggling mentally. This condition is so cruel and has taken 3 people i used to regularly chat to who have all taken their lives in the last 2 years.
Every day i am struggling. I cant believe this has happened to me.
susanne says
Very sad Spruce The ‘data’ the regulators collect should not just include the stats but the life experiences that go with them – hopefully you will keep telling the truth of how it is – with best wishes
Take care
Mikhail says
A sad time indeed when news of another suicide is tallied among the others I’ve witnessed.
It’s been about two years for myself, with absolutely no recovery in sight. I have everything I need to “get on with it” save for the courage to do so.
Currently I’m cleaning out my room, giving away what I don’t need and thinking of how to divide up what’s left after I’m gone. I’d at least want a clean and empty space left behind, if only to symolise the utter void that persists deep within my heart.
Provided I do not cremate slowly in Hell, I’d like to meet some of those who’ve self-terminated. I’d tell them about how strong they were and bid them an eternity of peaceful sleep.
I think you’re very strong too, Spruce. As much as you may think eking out such an existence is the antithesis of power, the fact you’ve gone on for so long is remarkable.
Spruce says
Thanks Mikhail.
Try to keep going though, and don’t give up, although i know how hard it is.
There must be a way out of this nightmare somehow.
Future says
“But in some unpublished phase 1 trials, over 50% of healthy volunteers had severe sexual dysfunction that in some cases lasted after treatment stopped.”
I would like to know the source.
Dr. David Healy says
The source is me. As an expert witness i get to see things you can’t and no other doctor can. This is part of the problem – these trials in volunteers – so no diseases on confidentiality issues involved – should be in the public domain but aren’t
David Healy
mary H. says
Am I right in thinking that there are other ‘expert witnesses’ who will have also seen this evidence? What is their view of this secrecy which is such a frustrating issue?
I have no doubt that you will have tried every possible avenue to correct this secrecy. Is there a possibility that all sufferers – anonymously if necessary – could have their suffering exposed through Samizdat Health, in printable form, so that the rest of us could at least share with a wider audience? Spruce, for example, has so much knowledge and ‘insider information’ which needs to get out to the clear light of day.
susanne says
With ref to Isotetrinoin again
An expert group has been reconvened to review recent safety data relating to the acne drug isotretinoid and evaluate the risk of sexual and psychiatric adverse effects, including suicide reactions. In 2019 12 deaths were recorded among people to whom isotretinoin had been prescribed, 10 by suicide,
In guidelines published by Alliance Pharmaceuticals – ‘Advice For Men -‘ the levels of oral retinoid aRE/ too low to harm their partner’s unborn baby.’ – So how many studies are carried out to see if there are problems down the line?
‘The available data SUGGESTS that the level of maternal exposure from semen is not of sufficient magnitude to be associated with tetrogenic effects’. – Again how would they know unless there is continuous monitoring?
Men should not donate blood during or after taking the drug for 4 mths . A drug as toxic as this is allowed to be prescribed for pubertal youngsters but not before – all adolescents don’t develop at the same rate but also they will not necessarily be knowledgeable about the sexual changes which it would be expected they will be experiencing – and are not .so that the first signs of harm may not be realised until they become older and forming relationships . Adolescents don’t all have parents or others they would discuss sexual issue with Even if they suspect something is wrong they would likely not talk about it and be fobbed off if they did My point being there can’t be any reliable information about the harms caused down the line by Isotetrinoin given to children unless they are reporting the link andsomebody recognises it There must be untold numbers just putting up with it.
Heather R says
There are indeed untold numbers just putting up with it, as we know only too well to our cost. They are dying in droves. And what the hell can we do? Seven long years of active protest, and before us, back to 1982, others trying just as hard.
We need a NEW treatment to bump this thing off everyone’s radar. And we have a plan….more ideas on how, to come.
AC says
Last week, Frankie ( From the group ‘The Saturdays’ ) who is a well known extremely attractive Celebrity, married to a well known footballer, spoke out about her struggles with her MH and in particular her struggles with depression. She had been on quote’ 10 different anti-depressants’ which according to her had caused sexual dysfunction, which in turn had put pressure on her husband ‘ I tried to reassure him it was the medication not me’.
She told her Daily Mail audience that she expected to be on anti-depressants for life.
So does that mean that sexual dysfunction is an acceptable side affect of ‘depression pills’ Frankie is a young woman
Its one thing for the mainstream media to suggest sexual dysfunction is a side effect of ‘Depression’ quite another to suggest one should put up with this if you decide to take medications which cause this…….let alone the fact that Frankie and others could find sexual dysfunction to be permanent long after their depression passes…….
Professor Healy I wonder how willing ‘Celebrities’ would be to talk about sexual dysfunction on SSRIs…….They all love to talk about their MH…their experiences with anxiety, breakdown,depression………Even Royalty say loud and proud…’Its good to talk’……..
mary H. says
I wonder if anyone suggested to her that doing away with all ADs could be her way forward?
I agree that celebrities love to talk about their MH – seems to be the ‘in thing’ at the moment, mainly because of Royalty’s opening up about it no doubt. There was a time, not that long ago, when many celebs spoke of “being brought up in poverty”, then came “abuse” – now we’re on MH, where next I wonder?
Wouldn’t it be great if it was PSSD and akathisia and that they were willing to pour a little of their cash into the Rxisk Prize Fund.
As for ‘it’s good to talk’ – of course it’s good but where is there for people to turn to when that is their need? They turn to friends/ family but what are they likely to suggest if things are really bad ? “You need to speak to someone who can help you beyond what I can do”? Who? Where? – community mental health teams are more or less gone in our area……..and yet, offering a group as ‘a place to talk’ falls on deaf ears!
L says
It’s not easy to put our face on it. I am shy and I live in a small town, my parents, my acquaintances…I think about this.
And everyone will have a similar justification: family, friends, job.
Let us strive to do everything possible and to bring out a little courage in the face of something so neglected, terrible and criminal that has hit us.
I’d be curious to know the ideas of what could be done once we put our face. Each of us could have their own way to do it.
susanne says
Mad in America SCIENCE, PSYCHIATRY AND SOCIAL JUSTICE
Wendy Dolin – Making Akathisia a Household Word
James MooreBy James MooreJanuary 25, 2020
This week on MIA Radio, we interview Wendy Dolin founder of the MISSD foundation. MISSD stands for Medication-Induced Suicide Prevention and Education Foundation in Memory of Stewart Dolin.
Dopagon says
Sexual dysfunction is obviously massively important but I have to be honest here and say that people in the community feel we’d like much more to be done in highlighting the anhedonia and emotional numbing that arises from these meds. Which dare I say,many deem far more troubling/torturous than genital numbing or dysfunction. Everyone I speak to,in fact.
It’s a major reason why people want to kill themselves. I would argue even more so than the sexual issues.
Sadly we lost a forum/discord member called AnhedonicApe a couple of weeks ago. He was bedbound due to anhedonia, much like myself. I know that he desperately wanted more recognition for the anhedonia side of things.
A lot of us just can’t function at all anymore and feel as if we are already dead or in a coma; it impacts everything.
Because of the severity,many in the community feel the condition should be renamed to better reflect and accommodate hedonic and emotional blunting. As not to disclude people who may only have anhedonia or even both conditions.
Being unable to feel love, pleasure or basic human emotion is a burden none should bear. But all the media want to talk about is the sexual side of things?
I too have been wrongly gaslighted by Psychiatrists and accused of being depreseed/delusional. Even though rat studies and countless anecdotes support my argument. I have lost half my twenties to this condition and it’s traumatic.
However thank you for your work in trying to bring recognition to our suffering Dr Healy.
Dr. David Healy says
This issue of emotional blunting is one we will pick up on soon. There is no question but that most people with PSSD have emotional blunting and depersonalisation and anhedonia. The trouble is focusing on these symptoms is not a good place to look for an answer. Many drugs can or do cause emotional blunting, depersonalisation and anhedonia but don’t cause PSSD. And its clear there are a number of other Enduring Sexual Dysfunctions that do not cause neither emotional nor genital numbering.
From a research point of view, the need is to find a distinctive feature to the complex of things that happens in this condition – one that a research group can focus in on – and then to ensure that everyone the research project recruits has this feature. Genital numbing seems the best bet from this point of view. Its a very clear cut thing that can be put in front of researchers and regulators and companies as a challenge – emotional numbing is something that leaves them too much wiggle room and they can say but this occurs in other conditions and after other drugs, so how do we know its linked to SSRIs.
So the focus here on genital numbing is not one that should be read as saying the almost invariable emotional numbing isn’t just as important – its a matter of tactics.
David
Heather R says
Please forgive my naiveity in putting down some thoughts. I am not a scientist, biologist etc like my son was. But I’ve been trying to find the layman’s common factor between all these effects as listed above. Is it that various types of steroidal effects are being triggered in the body by all these difference medications? I know that persistent genital arousal can occur on Prednisolone. If one looks on Wikipedia at all the complexities of steroids, and how they are expelled from the body via the enzymes in the liver, or are supposed to be, and all the different hormones they affect, do we need something which can reverse the steroidal effect. Are steroids much more dangerous and far reaching than we realise? I know I for one cannot tolerate them. One short 11 day course in 1994 pitched me into mental and physical side effects that it took me almost a year to recover from, mostly using B vitamins to balance out the gut flora etc. It was a living hell. I was totally unprepared for it. The drug had simply been given to me for an allergy to grass pollen causing wheezing. Are isotretinoin and antidepressants behaving like steroids, and to remove the damage like PSSD and PRSD, would an antidote to steroids work? And if so, is there such a thing? Please excuse me if this sounds like nonsense. I am just feeling my way and trying to learn. Are some of us very sensitive to steroidal effects from drugs, whereas others can cope with them?
susanne says
David The Rxisk Prize seems to be stuck – it’s been 62,900 dollars for many months. Are there any other options for research being researched?
Dr. David Healy says
Suzanne
Yes it is stuck but we are chasing some further options re fund-raising and also have a few people chasing possible treatments and others chasing political angles. So its not just being let sit there – we are actively keeping on eye on what best to do
D
mary H. says
I wonder if a regular (maybe quarterly) comment of news regarding what may be in the pipeline would help? Directing people to the Prize Fund page is unhelpful when there’s nothing new to attract their attention. A “breaking news” type of slot running at the top perhaps? Or, maybe, a few words outlining in which ways volunteers have already raised money?
L says
https://notiziescientifiche.it/disfunzione-sessuale-post-antidepressiva-scienziato-chiede-maggiore-riconoscimento-della-condizione/
Italian article
susanne says
Re: Social media companies should be forced to share data for harms and benefits research, say psychiatrists
Re: Social media companies should be forced to share data for harms and benefits research, say psychiatrists Elisabeth Mahase. 368:doi 10.1136/bmj.m209
Dear Editor,
Psychiatrists seem more concerned about hidden harms from digital social networks than about hidden harms of depression pills from most pharmaceutical companies.
They continue to tolerate sharp increases in prescriptions for antidepressants, despite refusal of companies to disclose all research data.
30 January 2020
Stavros Saripanidis
Consultant in Obstetrics and Gynaecology
C says
To realise that I took the drug shortly after the “sexual dysfunction may persist after discontinuing the treatment” label was added and that my pack did not have that warning. Just very painful.