New paper
“If you wish to have such “syndrome” continue what you are doing … read obscure studies and reviews in obscure databases and I can guarantee to you that you will have it till the end of your life!”
Anyone who has experienced a serious side effect from a medication will know how difficult the conversation with your doctor can be.
In our new paper, “Post-SSRI sexual dysfunction: Patient experiences of engagement with healthcare professionals”, 62 people from 23 countries tell us about their experiences of trying to get help for their condition.
Our manuscript is Available Here.
We are grateful to all of those who contributed by providing details of their experiences. We hope this paper will not only help to raise awareness of the condition itself, but also bring greater attention to the difficulties that patients can face when trying to seek support.
Please note that we are still accepting donations toward the RxISK Prize which is aimed at finding a cure, and would welcome any contributions.
Clinical testing
Despite EMA’s commitment to ask companies to update drug labels, PSSD sufferers are still likely to need evidence from a test in order to be taken seriously by health services.
Astonishing as it might seem, we know little more about the sensory side of the peripheral nervous system, touch in particular, than we knew 100 years ago. Neurology services have great tests of peripheral motor but not sensory function.
Few people with PSSD know this and are pleased to get any referral for a test, but despite obvious genital numbness, abnormalities are rarely or inconsistently found on standard tests of peripheral neuropathy or on sensory evoked potentials, sympathetic skin responses or MR neurography of the spinal cord, which risks providing ammunition for anyone saying your problems aren’t real.
The genital changes include:
- decreased somatic (tactile) sensation
- decreased erogenous (sexual) sensation
Erogenous sensation is poorly understood and there are currently no available tests. However, quantitative sensory testing (QST) of the genitals is a well-established method of assessing somatic sensation, typically involving the use of warm/cold temperatures and vibratory stimuli.
Using a form of QST, studies from the 1990s showed that SSRIs decrease somatic genital sensation while taking them. Every report we have had of QST testing of the genitals has found abnormal results in PSSD.
The tests usually done (sensory evoked potentials, sympathetic skin responses, etc.) do not directly measure somatic sensation and as mentioned don’t pinpoint a problem.
Blood tests for hormone evaluation are of limited value. Loss of libido and other symptoms caused by the condition do not appear to be mediated by standard hormone levels. Some patients have slightly lower testosterone, but this is likely a consequence of the condition rather than the cause.
We have seen some evidence that assessment of nocturnal penile tumescence can reveal an abnormality, but it’s not known if this is common to all male PSSD patients.
In summary, it would be helpful if you could get your doctor to refer you for QST genital testing and let us know what is found and how the testers or your doctor interpret the results.
L says
Reading so many unjust, obtuse and asshole answers with respect to our experience of PSSD, in this case gave me satisfaction, because it is clear how absolutely wrong they are.
Much esteem for David Healy, Joanna Le Noury and Dee Mangin
for the heart and courage with which, even without funding, managed to give birth to such an important and true analysis, giving the floor and attentive listening to those who until now have endured frustrations, teasing and humiliations by specialists.
This can be like our kick in the faces of all those superficial, arrogant, in bad faith and happy-to-remain-ignorant doctors, who believe that their answers hit weak people without being interpreted for what they really are.
But I really hope that this article will open the eyes of all those specialists who wish to be correct, attentive and honest, despite up until now, their instinctive responses may have been the same as those we already know.
This is to be printed in many copies and brought to the offices of general practitioners, psychiatrists, psychotherapists, sexologists, andrologists, gynecologists, urologists …
Reading the answers received from you others, and thinking about how you have been around for many medical studies bringing this delicate problem, hoping and despairing, and without finding understanding and solutions, I felt tenderness for you and solidarity.
This study is a gift for me, I am proud to have participated and I thank everyone who participated.
Derek says
I just turned 17 and I have PSSD. Everyday is a complete hell and pure torture. Yesterday when I almost jumped in front of a train I got a thought: “What if all the people who suffer from this get together and make this public. And that everybody needs to know about this.”
We need to get those fuckers who make these “medicins” locked up.
Lets spread this, the whole world needs to know about this.
I’m not killing myself because of a pill I took 3 weeks.
Fuck dying, I want to live.
To everyone who suffers: this is not your faith. We are strong if we stand together.
Who’s in?
Singh says
Right bro…
Edoardo says
Hey Derek, i was 17 too when i started to take effexor, stopped at 18 and here I am writing on this page now.. Its been 4 years since your reply.. How it is going now? Any better?
A psychiatrist i have just seen proposed me to try vortioxetine wich he said has “no sexual side effects” , i think i will since im already ruined so cant get worse. I actually also read an article that states vortioxetine could reverse pssd, that would be a miracle, id have tears of joy for days if true.. Here is the link… What do you all think about this? https://pubmed.ncbi.nlm.nih.gov/36135826/
Dr. David Healy says
Edouardo
Vortioxetine causes PSSD
David
Jj says
If I got back on my antidepressant would the pssd go away …was it from stopping it and if so if I got back on it would it go away?
Dr. David Healy says
no it wouldn’t go away
D
okok says
It’s possible. Because of oppositional tolerance. You have to take it for months. Your brain will downregulate serotonin receptors and the production of serotonin etc. And when you stop your libido will be back to what it was or even better.
But I wouldn’t recommend ssri’s. You’re not going to feel the same when you stop taking them after a few months or years, and you’re going to obsess over this. They change many things, and that’s why they work, if/when they work, for some it’s PSSD, but others might get something else that is not as bad. And it takes time to return to normal, some things could even be permanent.
Rose says
Just going on record(even though these comments are very old). Going back on the medication does NOT fix it. I’ve been back on my SSRI for a couple years now with no improvement to what I caused when I went off them. Definitely scared to ever stop taking them again in fear of making it worse.
annie says
This might seem like one of the worst experiences of SSRIs, Sexual Dysfunction.
It certainly is for those experiencing it.
“Quacks on the internet”
If you did a questionnaire for violence, suicide attempts, depersonalisation, etc., you would likely receive similar reports.
Why do drugs like Seroxat bring out the worst traits in people who ‘normally’ would not behave as they do.
Whole armies, nay, battalions behave as if its the Crusades, all over again.
Worldwide, seemingly intelligent,well-qualified, people get on their podiums and announce
“the people are lying”
Armoured-up, jousting-sticks aimed, on their high-horses – mocking, taunting, goading
If they don’t understand it, they should grow up and be inquisitive and sympathetic.
That is called “man-up”
The effects of the language coming out of the mouths of doctors is increasingly derisory and if you keep pushing – you will be punished.
“Quacks on the internet”
They don’t even realize how dangerous they are, your life is in there, in that small room, just the three of us – the patient, the doctor and the computer …
It is a Doctors’ job to do a treatment plan for any ailment; being almost unanimously hostile should never be a part of any judicious ‘treatment’ thereby causing intense distress with often horrific repercussions…
L says
who with pssd did the quantitative sensory tests on the genitals, do them in clinical or research settings? in other words, is it a matter of finding a specialist who does this or persuading one to try at the genital level?
Mike says
I find it hilarious that they have the balls to out right deny it when they test them on rats and it says on every product label that these drugs are thought to work on serotonin in the brain, but exact mechanism of action remains unknown. How can they deny it when they dont even know what the drugs are doing. It is the most corrupt and cowardly response there is. How can they tell you that our disorders are neurodegenerative when they have no long term studies to show unmedicated people with anxiety or depression having brain shrinkage. Makes no sense.
susanne says
Mike -There are better warning labels on boxes of rat poison.. To some of those who have knowingly sold drugs which cause harm it seems human life is as dispensible as a rat’s. Unless they can be used as lab rats. (this is not to devalue the lives of millions of rats who are being used in the most vile experiments which don’t map onto a real human being – but to make the point)
Carla says
Just having treatment because they are available can be the worst of all worlds.
Are we informed about all the risks when ingesting prescribed medication or undergoing an invasive procedure?
Just sign on the dotted line and do not worry about what is to come?????
MattD says
At the bottom of it is just the stupid superstition about depression and “mental illness” itself. As long as they have the tag, they can subsume anything they want under it, and be it just their general disbelief and disrespect of the other person… It’s meaningless bullshit. Alone the idea of “serotonin solution to everything”, “dopamine bad”. Such sheer idiocy, wow. Or “caring about anything is pathological”… And yll that applies to anyone, by the way, it doesn’t truly have to be “grotesque”, as they like anyone to believe (to be taken seriously themyelves…), to begin with, but they lure anyone with cheesy clichés of “understanding”, just to put everyone in the box and ruin their lives.
It’s not science, not even soft science or academia, just self-importance and (common-sense) sociopathy of people of this field…
RyanS says
Honestly pathetic, at this point patience and avoiding triggers is what’s best to do for those affected by pssd.
I did deep research and the word Edovis was in nearly most “cured” pssd patients list, any idea if this is just advertised or could it actually work ?
Murad Sawalha says
I’ve also seen this, want to know if someone took it…
Dennis says
Any success in trying Edovis? I’m talking to my doctor about it now.
Spoe says
I have pssd since years and know i have test EDOVIS about 5 weeks and im very happy. I think i get back my old life.
PSSDBoi says
That’s fantastic news! Thanks for sharing!
Nik says
So how did EDOVIS finally helped you? I’m thinking on taking it too. How long did you took it?
Mikhail says
I wanted to give thanks to Dr. Healy and the participants of this survey.
As one who’s had PSSD since May of 2018, I wish I’d seen a document like this before I spent time in a partial inpatient programme last year. This was some time after I learned about PSSD and was barely functional after severe withdrawal.
I was not only misdirected in the office with irrelevant questions and feigned concern, I was also told that withdrawal did not last more than several weeks (not the months I’d gravely suffered) and nothing was said about my lasting adverse effects, only blithe recollection about comparably lesser ramifications like brain zaps. While the psychiatrist boasted his claim of being among the best on the east coast of the US, he blithely answered “I don’t know” when I asked how the Sertraline he prescribed was going to change my brain.
When he was audibly detailing my erectile dysfunction and other problems to his staff in an adjacent room after our meeting, the university psychiatry pupil sitting in on the session was trying to coach me into taking these pills.
Some weeks hence the solution to my non-compliance was to jam vortioxetine samples into my hands before rescheduling. I didn’t take a single pill and never looked back.
It’s depressing to know that I’ll never regain my cognitive or sexual functionality. As a man in his late twenties with no career prospects and what seems to be a lifetime of unemployment and parasitic ennui, it’s no wonder I pray for death and ruminate on suicide daily.
Spruce says
I can empathise Mikhail. I too have almost daily thoughts of suicide, and feel on the outskirts of society because of long periods of being unemployed, and having PSSD.
On top of that my mums side of the family are really judgemental, and snobby, and openly look down their nose at me, which makes me feel more misunderstood and angry.
I stopped talking to them while going through the years of benzodiazepine withdrawal, as they would always complain to my mother about why i didn’t have a job, and have always refused to accept there was anything wrong with my health.
Also there have been awkward questions about why i haven’t had a girlfriend for years, and every single one of my cousins etc have got married or have long term partners and most have had children, and it would be just too awkward to be around extended family living with the PSSD. I really couldn’t bring myself to tell them about PSSD, because some of them can be quite unpleasant, and i am not sure they would even believe me.
Also my sister really doesn’t understand what has happened to me, and just before my dad passed away in 2017, she told him that she felt most of my problems were caused by me being “immature”, that i needed to “grow up”, and she also told him that i had “never done anything with my life”. I have tried to explain to her what has happened to me with the benzodiazepine withdrawal, but she really doesn’t understand how bad it was, and doesn’t want to listen. She also told my mother last year that she thought the fact that i hadn’t had a proper job for years was “pathetic”. So that was nice.
My dads side of the family stopped talking to me shortly after my dad died in 2017, after a number of arguments and unpleasant emails over some grievances they had with my mums side of the family, which had nothing to do with me. I had got on quite well with them for years before this.
In some ways i feel the way i have been treated by my own family, has been just as bad as how i was treated by the medical profession, because it feels more personal. Families are supposed to be there for you, and are supposed to support you.
Since 2018, the only person from either side of my family who will really speak to me is my mother. Once she is gone, i literally face a future with no family, few friends, on top of the PSSD, and having lost over 12 years of my life, and counting.
People have suggested starting my only family, but i cant see this ever happening unless the PSSD resolves. I have tried having relationships with women over the years, but it is very difficult with the PSSD.
Since 2018, i feel the loneliest and most isolated that i have ever felt, and cant see anything in the future apart from slowly getting older, more angry and bitter about everything i lost from PSSD and benzodiazepine withdrawal, and becoming more and more isolated.
I will do everything i can to avoid this outcome and turn this bad situation around, but on some days it all feels hopeless.
JR says
Hello,
Has the use of viagra or cialis improve the sexual function temporarily? Or have neither of these been tried?
susanne says
How to drive someone into a corner or into depression or worse
the potential of having the label of ‘psychosomatic disorder’ attached by ignorant closed minded to say the least ,’professionals’ It is sometimes used covertly so as always important to read medical notes. It is a favourite tag used by those with an interest in psychoanalysis, especially if they have friends/relatives/colleagues with personal interests to pursue,working in departments needing ‘referrals’/research rats/fodder to bulk up specialist publications. claims to ‘successful treatments’ to pursue and defend their personal interests and funding.
If someone persists the next label either openly or covertly applied can be ‘personality disorder ‘(a GP in N London suggested if GPs suspected PD they should put a tag, covertly on a person’s file. So much for openess and transparency and trust blah blah.. In the meantime the possibility of getting the problem investigated goes down the drain of ‘psychosomatic’ or’personality disorder’
Carla says
Sorry David, the previous comment had too many typing errors. If you would like to submit the comment please refer to this one.
Yes, Matt, there is definitely a power imbalance going on when some professionals refuse to acknowledge that the medicines they prescribe induce PSSD and other health disorders.
Why would anyone go against the tools that are their bread and butter?
Mental health, does not discriminate.
We are programmed to believe that a ‘pill’, (whatever it may be), is a panacea to all our problems.
Show us the tests that conclude that when someone is depressed, there is a serotonin or chemical imbalance of the brain?
If we did not have all the triggers in our life that produced unnecessary stresses, we would be in synergy with our life and develop a more harmonious balanced lifestyle.
Perhaps, having too many prescribed medicines + unnecessary stress/pain, induces neurological disturbances.
This is the problem with labels and misdiagnosis.
From my understanding, sociopaths, psychopaths and other disorders, may be further amplified by prescription medicines.
It may bring out the ‘darker side’ of someone’s psyche!
Are many mental illnesses induced by prescribed medicines or do people have this belief that it placates an individual, just so that they comply with the rest of the society, (whatever, that may be!)
Could the combination of medicines + many processed foods + the toxic water we drink + stressed lifestyles = poor health outcomes
Science, in some instances, is very doubtful, in my opinion, at this very moment, in time.
If we have professionals fudging and blemishing data, what hope has the human species got?
Psychopaths, are born and bred and are highly intelligent individuals and if I have to trust my good health with some that have mythomania or some mental disorder, I would question again and again, am I in safe hands or should I run………………!
Trust is a double-edged sword.
I expect nothing but honesty when it comes to my health.
RyanS says
A response asking for a qst machine for use or for sale of necessary—
Medic USA replied ;
Hello. Your emails/queries to this point have not included needed information, such as institution/organization details – where such a system would be used or by whom purchased, etc.
In that regard….
Are you writing from / referring to use in the U.S. or elsewhere, as in UK (noting Professor Healy’s location)? – – – – and where would a unit be used….by whom…and purchased by what organization;
noting that this piece of medical testing equipiment and should only be used in the care of a licensed medical professional; not by a patient, etc.
Thank you.
Phil Brooks
Obviously someone who knows how to use it or a “health professional” is needed to use the machine accurately.
How would it be in use and who would test the patients using the machine ?
David says
PSSD ruined my life over the time span of a few months and made me bedbound permanently . Thanks psychiatry, appreciated.
Liz says
Me too. Severe chronic fatigue. Lexapro 6 months. F%#* psychiatry.
annie says
On a sticky wicket here; I don’t believe there is much truth in this statement :-
Professor Helen Stokes-Lampard, chair of the Royal College of GPs, said: ‘GPs are specialist prescribers and will only recommend medications based on the individual circumstances of a patient, taking into account physical, psychological and social factors, and after a full and frank discussion around treatment options.
GPs are leaving thousands of patients in the dark about the crippling side effects of antidepressants as just one in five are told of the potential risks
https://www.dailymail.co.uk/health/article-7525599/GPs-leaving-patients-dark-effects-antidepressants.html
GPs currently receive no mandatory practice based training in mental health
Do they really need to be spoon-fed, what should be ‘taking the initiative’ …
whocaresinsweden.com
Allt fler upptäcker tyvärr att de inte får tillbaka sin sexualitet när de slutar med SSRI, antidepressiva medel. Post-SSRI sexual dysfunction, är en mycket tragisk biverkning som tyvärr svenska läkare inte varnar för. Varför, kan man fråga sig?
More and more people discover that they don’t get their sexuality back when they end up with Shri, antidepressants. Post-Shri sexual fiction, is a very tragic side effect that unfortunately swedish doctors do not warn about. Why, can you ask yourself?
PSSD Patient Experiences
susanne says
She is also telling people to take copies of their notes when referred to consultants – good advice – especially for those with the devices which can do that if they are computerised- they will have their medical notes without going through the palaver of applying for them and with the backing of H S-L if obstructed. Her reason is that the notes are taking too long to get back to GPs but it offers a good opportunity for getting the notes first hand , Get the codes they use to define us too theres been some confusion about providing those
Spruce says
Well done to Rxisk, Dr Healy, and anyone else involved for getting this paper completed. Another step in the right direction.
Jayme says
Wonderful work done by Dr. Healy and the RxISK team on bringing to light an additional devastating ADR related to SSRIs for it seems many many people. I’ve been fortunate to never have been placed on an SSRI for any extended period of time but can appreciate the experience of ADRs and side effects with Depakote, my kryptonite. I am slowly tapering off this and aside from terrible side effects while on the drug (for years mind you), the withdrawal effects at times are equally bad. My experience with my doctors echoed many of the negative aspects of patient experience in the PSSD study. The most surprising and devastating denial of withdrawal experience was from my long term psychologist whom I credit with really saving my life many moons ago. That happened today – her demonstration of ignorance and avoidance, denial. Kind of rough but I am fortunate in that I have good supports and I am a very strong person now. I guess I’m posting to let others know they are not alone.
susanne says
Re ‘ Frequently asked questions.’ – on Sudoscan website
What drugs can interfere with SUDOSCAN results?
As SUDOSCAN is based on measurements of sweat glands innervated by cholinergic small C fibers, drugs with high anti-cholinergic effects can influence SUDOSCAN results.
Thus tricyclic antidepressant agents (in particular amitriptyline), can significantly decrease ESC measured by SUDOSCAN. It is recommended that patients on such medications omit the drug for a period of 2 ½ half-lives (e.g. 48h) prior to SUDOSCAN testing.
If this is not possible results must be interpreted with caution. The effect of medications on ESC measurements is a key point and is under continuous investigation in ongoing studies.
Is Sudoscan;s unwillingness to get involved something to do with the fact that they have actually done some testing on effects of antidepressants. If the testing has revealed a link to nerve damage to genitals as even probably caused by anti depressants – is that why no information on the adapted device or research material is publicised anywhere? And why the Rxisk enquiry has resulted in doors being slammed in the face of those who contact them? Sudoscan could even now after reading how genuine the suffering is for so many people – drag up the sudoscan with adapters from the basement somewhere so someoneone could get some testing started. Come on Sudoscan have some balls , have a heart.
Spruce says
I agree Susanne.
When people say their hands are tied, it is often a case of i wont help, rather than i cant help.
If Impeto medical really wanted to help, i believe they could. Even if to just let a few people with PSSD go over to Paris and get tested as a one off, to see if any abnormalities could be detected on their sudoscan machine with the genital adapter.
It wouldn’t be too difficult to have this arranged.
annie says
Acne drug, suicide and impotence
Channel4news
Acne drug ‘linked to at least 14 deaths’ this year
Victoria Macdonald Health and Social Care Correspondent
A powerful drug presribed for acne is being linked to at least 14 deaths this year – mainly from suicide. Manufactured under the names Roaccutane and Accutane, the drug is often credited with yielding miraculous results.
Yet the medicines regulator has now reopened an inquiry after being contacted by patients, including young men who claim to have been left impotent and families whose children have killed themselves.
https://www.channel4.com/news/acne-drug-linked-to-at-least-14-deaths-this-year
susanne says
This is a long tirade published as an r.r. by thebmj
The author(s) need to reflect on their understanding of ‘ideology’ as used in this perjorative way to undermine evidence based claims by P G and colleagues. Yet again unless people read the material he criticises they have no way of knowing the possible serious consequences or even of giving informed consent, Could J.S. and co. provide the actual data for their research? And please include the authentic unadulterated feedback of those who took the drug.
Lost in translation(al neuroscience)?
Re: Esketamine for treatment resistant depression Sameer Jauhar, Paul Morrison. 366:doi 10.1136/bmj.l5572
We thank Gøtzsche et al for their comments regarding our Editorial [1], though do need to correct a number of erroneous assertions, that appear related to ideology as opposed to basic principles of clinical medicine, neuroscience and pharmacology.
Gøtzsche et al’s argument loses internal consistency as early as the second paragraph. They write that a drug cannot have a rapid, “dramatic” effect on depression (according to “common sense”) yet contradict themselves by citing data which, in their own words, shows that ketamine has a rapid, “colossal” antidepressant effect.
They state that “ketamine seems to work mainly through stimulation of opioid receptors”, citing a study where naltrexone was added to ketamine and attenuated its antidepressant effects [2]. Ketamine is an acknowledged non-competitive NMDA receptor antagonist [3]. Whilst the naltrexone blocking study is interesting, all it indicates is that ketamine may have downstream effects on this system. The extrapolation that ketamine can cause depression because opiates may cause chronic depression is illogical – the pharmacology of both compounds is fundamentally different.
Having appeared to cede on the question of efficacy, Gøtzsche et al pour cold water on the ketamine effect itself, arguing that it is not genuine anti-depression per se, but acute euphoria which is being measured. They pursue an odd strategy, apparently naïve to basic molecular pharmacology, by lumping ketamine, alcohol, morphine, cocaine, ecstasy and MDMA (sic) together in a common class of acute euphoriants. Having done so, they speculate that the whole class, ketamine included, masquerade as antidepressants during acute euphoria, but reveal themselves over the longer-term as harmful, addictive, dysphoric drugs. This is the basis of their appeal that the development of ketamine as a “quick fix for depression must stop”.
When research evidence is taken into account, Gøtzsche et al’s argument falls apart at the behavioural, clinical as well as the molecular level. For example, Berman and co-workers showed that after a 40-minute infusion, the antidepressant effects of ketamine actually increased over the course of the next 3 days [4]. In another study, Murrough and colleagues gave a series of 40-minute infusions and were able to extend the antidepressant effect of ketamine to 2½ weeks beyond the final infusion [5]. The trials cited in our Editorial also show continued separation from placebo, over the course of the acute trials. These findings refute Gøtzsche et al’s claim that the behavioural pharmacology of ketamine follows an acute-euphoria/chronic-dysphoria structure, rather than being genuinely antidepressant. Murrough’s group went on to conduct a randomised trial which compared the putative antidepressant effects of ketamine with midazolam infusions, the latter serving as an active placebo. (Incidentally, midazolam comfortably fulfils the membership criteria for Gøtzsche et al’s acute-euphoric/chronic-dysphoric class.) The main finding, in a sample of 73 treatment resistant patients, was that ketamine markedly outperformed midazolam as an antidepressant [6]. Depression scores as rated by the MADRS at 24-hours post-infusion were 8 points lower in the ketamine group. Clinically, it is difficult to understand how Gøtzsche et al suggest alcohol could have similar acute effects to those seen in ketamine trials – clinicians are well aware that acute alcohol use is a risk factor for suicide in people with mood disorders [7], whilst ketamine has been shown to reduce suicidality [8].
Clearly Gøtzsche et al’s conception of a general class of addictive acute-euphoric/chronic-dysphoric drugs, in which all psychoactive molecules can be tarred with the same brush is too simplistic.
We are slightly surprised that Gøtzsche et al disagree with our suggestion that esketamine is less likely to be abused, on account of its cost compared to ketamine. They state, “the price of a narcotic cannot prevent widespread abuse.” There is no citation given, and evidence from the US opiate crisis suggests a relationship between cheaper heroin, availability and heroin-related overdoses, ie market dynamics do affect use of “narcotics” [9].
It is the case that Gøtzsche and co-critics have been well-publicised in expressing organised antipathy towards the range of physical treatments in psychiatry, including monoamine based anti-depressants, anti-psychotics and ECT [10,11]; their criticism of ketamine is by no means unique. Indeed, they go much further by arguing that psychiatric syndromes such as major depression don’t actually exist. Instead they appear to conceptualise a more pervasive “distress” which arises from Western-style economics and early abuse. Gøtzsche and co-critics appear to regard neuroscience as largely irrelevant for understanding psychological distress, and typically espouse socio-political explanations and interventions [12,13].
Certainly, the views of Gøtzsche and co-critics are useful in making psychiatry question itself. That said, the downsides of ketamine as a treatment for depression have already been factored in, as we made clear in our Editorial. Gøtzsche et al provide nothing new in terms of downside – the potential for misuse/addiction is well recognised, and the challenge, as in any other area of medicine is to mitigate against downside. In contrast to the views of Gøtzsche et al. it is clear that many patients with hitherto stubbornly resistant depression have benefitted from treatment with ketamine, when all other approaches have failed. To deny those patients an effective therapy, and to “stop” the further refinement of glutamate based anti-depressants seems very unfair, particularly as the objections to ketamine appear to stem from an ideological framework that doesn’t appear to be acquainted with (and/or acknowledge) the science of pharmacology at a behavioural, clinical or molecular level.
References
1 Jauhar S, Morrison P. Esketamine for treatment resistant depression. BMJ 2019;366:l5572. doi:10.1136/bmj.l5572
2 Williams NR, Heifets BD, Blasey C, et al. Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism. Am J Psychiatry 2018;175:1205–15. doi:10.1176/appi.ajp.2018.18020138
3 Hirota K, Lambert DG. Ketamine: its mechanism (s) of action and unusual clinical uses. British journal of anaesthesia 1996;77:441–444.
4 Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000;47:351–4. doi:10.1016/s0006-3223(99)00230-9
5 Murrough JW, Perez AM, Pillemer S, et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry 2013;74:250–6. doi:10.1016/j.biopsych.2012.06.022
6 Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry 2013;170:1134–42. doi:10.1176/appi.ajp.2013.13030392
7 Sher L, Oquendo MA, Richardson-Vejlgaard R, et al. Effect of acute alcohol use on the lethality of suicide attempts in patients with mood disorders. J Psychiatr Res 2009;43:901–5. doi:10.1016/j.jpsychires.2009.01.005
8 Wilkinson ST, Ballard ED, Bloch MH, et al. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. Am J Psychiatry 2018;175:150–8. doi:10.1176/appi.ajp.2017.17040472
9 Unick G, Rosenblum D, Mars S, et al. The relationship between US heroin market dynamics and heroin-related overdose, 1992-2008. Addiction 2014;109:1889–98. doi:10.1111/add.12664
10 Gøtzsche PC. Deadly psychiatry and organised denial. Art People 2015.
11 Read J, Cunliffe S, Jauhar S, et al. Should we stop using electroconvulsive therapy? BMJ 2019;364:k5233. doi:10.1136/bmj.k5233
12 Davies J. Cracked: Why Psychiatry is Doing More Harm Than Good
13 Read J, Mosher LR, Bentall RP Models of Madness: Psychological, Social and Biological Approaches to Schizophrenia (The International Society for Psychological and Social Approaches to Psychosis Book Series)
Competing interests: SJ is co-investigator on a research study in psychosis, funded by Alkermes. King’s College, London, has received fees from Lundbeck for lectures SJ has given on psychosis.
susanne says
Esketamine for treatment resistant depression
BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l5572 (Published 23 September 2019)
Cite this as: BMJ 2019;366:l5572
Opinion
A drug not a miracle—why we need a new system for monitoring
Re: Esketamine for treatment resistant depression: Putting drug company interests over the public good
We were surprised to see a BMJ editorial endorsing the latest pharmaceutical industry project to profit from the epidemic of modern misery 1. Esketamine has been licenced for Treatment Resistant Depression in the United States on the basis of flimsy evidence. Yet, the very existence of Treatment Resistant Depression is a testimony to the ineffectiveness of the pharmacological approach to depression. The scientific community should instead be calling on the European Medicines Agency to resist the proposal to unleash another chemical on the unsuspecting public that has unproven benefits and untested harms.
Interest in ketamine arose in part from the use of psychedelics as an adjunct to psychotherapy. The idea behind this movement is that undergoing an altered state of consciousness in a supported and therapeutic setting might provide a ‘healing experience’ 2. The administration of a limited number of intravenous ketamine injections has become popular in private practice, and is advertised as helping to break the cycle of depression 3. This approach may seem simplistic, but at least there is a transparent logic to it.
The idea behind esketamine is different; it is packaged as a new antidepressive agent for regular and long-term use. This is what makes it potentially profitable, because we know that people who start antidepressants often get stuck on them for years on end. Like other antidepressants, it is suggested to work by acting on some hypothetical neural mechanism of depression, yet it is more likely that its characteristic mind-altering effects simply mask or over-ride depressed feelings, in the same way that alcohol can temporarily ‘drown your sorrows’.
Despite this, evidence for the benefits of esketamine is very weak. Only one of the three trials of acute treatment presented to the FDA was positive, and the difference between esketamine and placebo was not large, especially compared to the large placebo response observed 4, and in view of the fact that blinding is unlikely to have been maintained. The acute trials lasted only 28 days; there is almost no data on the adverse effects of long-term treatment, yet we know from the recreational drug scene that ketamine use is associated with severe bladder problems and that prolonged use of euphoriant drugs like ecstasy can cause depression in itself 5. We also know that serious adverse effects may take time to come to light, as with tardive dyskinesia following long-term antipsychotic treatment, and serious and prolonged withdrawal and persistent sexual dysfunction following cessation of SSRIs 6. Leaving this crucial research until after the drug is licenced, as the FDA has done in the United States, and Juahar and Morrison propose for Europe, puts the public at risk and sets depressed patients up as unwitting guinea pigs in a huge and unregulated pharmaceutical experiment.
susanne says
In thebmj 8/10/19 This uses a cute little gadget to spray the stuff up the nose -a drug used to calm down horses
Re: Esketamine for treatment resistant depression: Putting drug company interests over the public good
We were surprised to see a BMJ editorial endorsing the latest pharmaceutical industry project to profit from the epidemic of modern misery 1. Esketamine has been licenced for Treatment Resistant Depression in the United States on the basis of flimsy evidence. Yet, the very existence of Treatment Resistant Depression is a testimony to the ineffectiveness of the pharmacological approach to depression. The scientific community should instead be calling on the European Medicines Agency to resist the proposal to unleash another chemical on the unsuspecting public that has unproven benefits and untested harms.
Interest in ketamine arose in part from the use of psychedelics as an adjunct to psychotherapy. The idea behind this movement is that undergoing an altered state of consciousness in a supported and therapeutic setting might provide a ‘healing experience’ 2. The administration of a limited number of intravenous ketamine injections has become popular in private practice, and is advertised as helping to break the cycle of depression 3. This approach may seem simplistic, but at least there is a transparent logic to it.
The idea behind esketamine is different; it is packaged as a new antidepressive agent for regular and long-term use. This is what makes it potentially profitable, because we know that people who start antidepressants often get stuck on them for years on end. Like other antidepressants, it is suggested to work by acting on some hypothetical neural mechanism of depression, yet it is more likely that its characteristic mind-altering effects simply mask or over-ride depressed feelings, in the same way that alcohol can temporarily ‘drown your sorrows’.
Despite this, evidence for the benefits of esketamine is very weak. Only one of the three trials of acute treatment presented to the FDA was positive, and the difference between esketamine and placebo was not large, especially compared to the large placebo response observed 4, and in view of the fact that blinding is unlikely to have been maintained. The acute trials lasted only 28 days; there is almost no data on the adverse effects of long-term treatment, yet we know from the recreational drug scene that ketamine use is associated with severe bladder problems and that prolonged use of euphoriant drugs like ecstasy can cause depression in itself 5. We also know that serious adverse effects may take time to come to light, as with tardive dyskinesia following long-term antipsychotic treatment, and serious and prolonged withdrawal and persistent sexual dysfunction following cessation of SSRIs 6. Leaving this crucial research until after the drug is licenced, as the FDA has done in the United States, and Juahar and Morrison propose for Europe, puts the public at risk and sets depressed patients up as unwitting guinea pigs in a huge and unregulated pharmaceutical experiment.
Eddie says
How long can they ignore that this destroys some people? Permanent sexual dysfunction is not an acceptable side effect. It’s worse than depression.
Jj says
Agreed all I want is to go back in time over n over in my head looking back I was fine now I’m 100 times worse
dn says
my life is too good enough before taking antidepressants and I thought doctor are God but know days my concept is totally negative about doctor he never says about pssd. He always says while talk about sexual side effect symptoms are normal after leaving taking antidepressants. I m 27 years old and I recently get married but each day I get die. I meet Endocrinology and urology but no any one medicine take to my past days.
I never ever know about pssd.Is there any one Treatment of PSSD ? I m shocked listening about it
jane says
yep someone should do something
yasin arabi says
hi everyone I had some questions 1-can this condition happen when for the second time you take the same SSRI for a period of time (Celexa 20m for 1month ) that you did take before (Celexa 20m 6month) and didn’t get any pssd from it 2-is it possible that your pssd start months after you stop the SSRI 3-even if you don’t use SSRI any more can your pssd become worse as time passes
DD says
In response to Yas in Arabic:
Yes, it is possible that you get it the second time. I took antidepressants 3 times in my life and didn’t get PSSD until after the third time. For your second question, I believe that PSSD does get worse over time after you stop taking the medication.