In a recent press conference, Emmanuel Macron said that France faced a Fertility Crisis and needed a Demographic Rearmament – see Liberty, Equality, Fertility. The Timeline below traces an important contribution from the medicines we take to that crisis, left unmentioned in his speech – and the role of an important player, the Industry making those medicines.
The Early Years
1930 French pharmaceutical companies made a speciality of research on antihistamines, many of which are now known to be serotonin reuptake inhibitors. These were the blockbuster drugs of the 1930s. It now looks like French laboratories created thalidomide before World War II. Thalidomide and SSRIs share common effects on sexual function, pregnancy, suicidality and peripheral neuropathy, with some shared mechanisms linked to these effects.
1952 French psychiatrists discovered the effects of Chlorpromazine, an antihistamine. This became the first antipsychotic and led to a flood of similar compounds – all endocrine disrupting – perturbateurs endocriniens. In the Sainte Anne Hopital, below in the dark coat is Jean Delay with Pierre Deniker on his left whose nursing staff make the crucial observations and Pierre Pichot on his right. See interviews with Pichot, Lemperiere on Pichot’s right and Thuillier on her right. For another view see Pierre Simon.
1956 Thalidomide migrated to Germany in 1954. The first evidence it caused birth defects was the baby of a member of staff in 1956. For 6 years and more Chemie Gruenenthal flat out denied it could cause problems.
1958 The first Tricyclic Antidepressant (TCA), Imipramine, derived from an antihistamine and modelled on chlorpromazine, launched. It was followed rapidly by Amitriptyline, Trimipramine, Clomipramine and later more selective noradrenaline reuptake inhibitors, Desipramine and Nortriptyline. Depression at this point is a rare disease. Pharma has little interest in it.
1960 A Randomized Controlled Trial (RCT) by Louis Lasagna shows Thalidomide is Safe and Effective.
1960 Frank Ayd reports Amitriptyline, his drug, can cause sexual dysfunction. Ayd found it easy to spot this even though melancholias (severe depression) being treated then also caused loss of libido. Doctors now cannot spot SSRIs causing more obvious sexual problems in conditions that themselves do not cause sexual dysfunction.
1961 Discovery of the anticonvulsant action of Valproate, in Lyon.
1961 Discovery of the role of SRIs in Obsessive-Compulsive Disorder in Lyon.
1962 In response to a Thalidomide birth defect crisis, the US Drugs Regulator, the Food and Drugs Administration (FDA) put RCTs in place to ensure Thalidomide problems do not happen again – the same RCTs Thalidomide looks perfectly safe in.
1966 Discovery of Valproate’s mood-stabilizing actions in Lyon
1968 Students protesting in Paris in 1968 ransack Delay’s office. From Japan to the US, biological psychiatry was seen as a problem. The camisoles chimiques then, now they make us Better than Well.
The SSRI Years
1968 Arvid Carlsson establishes Clomipramine, Amitriptyline and Imipramine as Serotonin Reuptake Inhibitors (SRIs). They are not selective to serotonin – would be called SNRIs now – but stronger than SNRIs and less side effects, perhaps because of their anticholinergic actions. Desipramine and Nortriptyline are selective noradrenaline reuptake inhibitors.
1969 Carlsson suggests making a selective serotonin reuptake inhibitor.
1970 Clomipramine (SRI) emerging as the most effective antidepressant. Carlsson creates Zimelidine the first selective SRI – an SSRI – adapted from brompheniramine an SRI antihistamine.
1973 Clomipramine and other SRIs used for Premature Ejaculation (PE). Only 10% of an Antidepressant dose 30-60 minutes before sex is needed to help – it numbs penis and delays orgasm.
1975 Clomipramine established as the best treatment for Obsessive-Compulsive Disorder (OCD).
1980 Valproate causes birth defects.
1982 Zimelidine launches in Europe. It is withdrawn 3 years later because it appeared to trigger Guillain-Barre syndrome in rare instances.
1983 First cases of SRI withdrawal induced persistent genital arousal disorder (PGAD) noted by Isaac Marks researching Behavior Therapy for OCD and finding people stopping their Clomipramine could have enduring sexual problems.
1984 Indalpine launches in France, Citalopram in Scandinavia, and Fluvoxamine in Belgium and Europe. All are SSRIs. Indalpine withdrawn 2 years later because of liver problems.
1985 Danish clinical trials show Clomipramine more potent than new antidepressants like paroxetine (a Danish drug). Is it a problem for companies producing an SSRI that is less effective and more expensive than older drugs? No. The older drugs are for severe diseases – we are aiming at the worried well and offering to make them Better than Well.
1985 Beecham, later SmithKline Beecham, later GlaxoSmithKline (GSK) Healthy Volunteer Phase 1 Study shows Sexual Dysfunction the worst side effect on paroxetine (later Paxil, Seroxat, Deroxat). Over 50% badly affected with some post-trial effects.
1985 Volunteers like Traci Johnson below in company SSRI Phase 1 trials – viz fluoxetine, sertraline, duloxetine, paroxetine studies commit suicide, become aggressive, become dependent after exposures of only 2 weeks.
1985 Western Male Sperm Counts Falling. Have more than halved between 1973 and 2010.
1985 Western Fertility Rates fall below the 2.1 Reproductive Replacement Rate. Scotland below is the country with the highest SSRI consumption in the UK and its fertility rate is now 1.3.
1987 By 1987 published SSRI trials show an excess of suicidal events on SSRIs.
1988 Having failed in efforts to market Prozac for hypertension or weight loss, Lilly begin ‘antidepressant’ trials. Marketing as an antidepressant has become an option because there is too much adverse publicity about dependence around benzodiazepine anxiolytics – tranquilizers. Drugs like Buspar have proven doctors won’t buy the idea of a non-dependence producing anxiolytics.
Lilly launch Prozac in the US, somehow generating the impression it will among other things cause weight loss. Later marketing spins it as making you Better than Well. We have known since the 1950s that drugs that cause some of us to commit suicide can make others feel Better than Well.
1988 Regulators and Companies get reports of Post-SSRI Sexual Dysfunction (PSSD)
1990 Teicher et al report convincing evidence Prozac causes suicide. Many other groups report similar findings including Healy and colleagues.
1991 Lilly invite Healy to be a consultant for them and among other things ask his opinions on how doctors and the public would view developing Dapoxetine, a short acting SSRI, for Premature Ejaculation.
1991 Human Fertilization and Embryology Act set up in Britain to license IVF services for women. IVF – in vitro fertilization. ART – assisted reproductive technologies. AMP – assistance medicale pour procreation.
1991 At launch sertraline (Zoloft) and paroxetine (Paxil) claim less than 5% of people in clinical trials have sexual issues and no mention of symptoms on stopping (SoS).
Lilly, Pfizer and SmithKline breach FDA regulations manipulating their clinical trial data to hide suicidal events. FDA staff write memos that FDA heads ignore.
1991 SSRI labels mention nothing about genital numbing, which affects 90+% – or genital irritability which can lead to PGAD. This irritability appears in the media linked to Prozac and is portrayed as a benefit – Prozac can give you more orgasms than you have ever had before. Yawn and you can have an orgasm.
1991 Genital numbing demonstrated on electrophysiology with clomipramine.
1991 The branding of crazily over-potent serotonin reuptake inhibitors as SSRIs originated in SmithKline’s Marketing Department, along with a resurrection of an idea about low serotonin being responsible for depression that had been discarded by science in the 1960s.
1992 Extension of IVF to men with poor quality sperm.
1993 Independent studies show up to 90% of people on antidepressants have significant sexual issues.
1993 SSRIs like paroxetine rapidly begin being used for Premature Ejaculation.
1993 GSK tell Investigators in Clinical Trials – Do not ask about Sex.
1994 Regulators have more reports in 3 years from doctors reporting paroxetine induced dependence than they had reports for benzodiazepine dependence over the prior 20 years.
1999 Withdrawal study shows 50% enduring sexual dysfunction on stopping SSRIs
2000 Healy sees his first case of PSSD. Some have had PSSD for 10 years by then.
2001 First academic article on PGAD – Leiblun and Nathan.
2001 Study 329, a study comparing paroxetine to placebo in depressed teenagers, is published.
2004 SSRI get a Black Box Warning for Suicide and Aggression. New York State lodge a fraud action against GlaxoSmithKline centered on Study 329 claims paroxetine works for depressed teenagers when it doesn’t.
It appears that:
- Almost the entirety of the pediatric antidepressant literature is ghost-written
- The gap between company efficacy and safety claims and the data is total
- Regulators like FDA know that published articles are false.
SSRIs Sex and Fertility
2004 National Toxicology Program report Prozac Rat Sexual Toxicity Study – Prozac wipes out male sperm and produces testicular toxicity.
2005 Prilogy (Dapoxetine), an SSRI, launched for Premature Ejaculation.
2005 FDA Guide for Industry on how to establish cause and effect relations between company drugs and adverse effects use the known effects of SSRIs on sexual function as an example.
FDA Guide for Industry on Good Pharmacovigilance Practice also uses the known effects of SSRIs on sex as an example.
2006 First academic articles on PSSD – Bahrick, Csoka and Shipko.
2007 European Regulators question Lilly about the Rat Study on Prozac and Male Sperm. They are concerned about the implications for Fertility – Cradle of Civilization.
2008 Senator Grassley brings PSSD to FDA’s attention who tell him they are impotent when it comes to deciding if SSRIs cause PSSD – Healthcare Gone Mad.
2009 The Kilker Trial gives a verdict against GSK in a case involving paroxetine and birth defects. These verdicts lead to hundreds of other settlements likely costing GSK somewhere around $1 billion. The evidence presented shows failure of implantation, increased rates of miscarriage and birth defects linked to SSRIs. The evidence later shows SSRIs cause behavioral defects in children and trigger alcohol abuse during pregnancy leading to Fetal Alcohol Syndrome in children.
Few doctors in the Western world get to hear about Paxil on Trial. A demonstration of pharmaceutical company abilities to shut down bad news.
2011 First academic article on Post Finasteride Syndrome (PFS) – a clinical condition closely related to PSSD caused by Finasteride – Propecia, a drug taken by teenage boys and young men to prevent hair loss.
2012 Regulators require Medical Label change to mention SSRI effect on Fertility. Companies do not add Fertility concerns or PSSD to Patient Information Leaflet.
2012 Growing reluctance in the media or medical journals to mention Sexual Effects or any Adverse Effects of SSRIs. We do not want to deter people from getting the benefits of antidepressants. Social media campaigns against pill shamers start.
2012 5 + million babies born by IVF – mainly Western.
2012 James Holmes Aurora shootings at the premiere of Dark Knight Rises – kills 12 injures 70. His plans to shoot people all emerge after he is put on Zoloft.
2013 DSM 5 mentions Post Treatment Enduring Sexual Dysfunctions.
2014 First mention of Post Retinoid Sexual Dysfunction (PRSD) triggered by isotretinoin – Accutane – in the academic literature. Another clinical condition closely related to PSSD. Isotretinoin is taken by young people for acne.
2015 Restoring Study 329 is published.
2015 Up to 15% of Western populations take SSRIs, making them effectively Infertile or at risk of complete loss of sexual function (PSSD) if they manage to stop treatment.
2016 Valproate causes transgenerational birth defects.
2018 RxISK petitions FDA and EMA re PSSD – FDA still sitting on it
2019 BMJ feature article on British people (and Westerners) not having sex as much as before. In the previous decade, there has been a rise in Asexuality, which in animals can be linked to SSRI intake during pregnancy. BMJ article blames depression but the worried well states that lead to antidepressants do not cause a loss of libido – SSRIs however do.
2019 EMA add PSSD to medical section of SSRI labels – not to patient information leaflet. RxISK has laid out in several posts just why EMA and FDA find it difficult to link drugs to adverse effects like PSSD – because they are bureaucrats. It is not their job to interview patients.
2020 Children of the Cure published – the background story to Study 329.
2021 Romain Schmitt dies while taking paroxetine – Deroxat. His parents find French doctors have difficulties blaming prescription drugs for any problems.
2021 Health Canada add PSSD to Antidepressant labels – but not to patient information leaflet.
2021 1-3% women have PGAD – SSRIs the most commonly identified trigger.
2021 100+ IVF clinics in the UK – 10+ million IVF births globally.
2021 La Peau des Pêches is published – puts Infertility on the map.
2022 Up to 6% of people may have PSSD on stopping SSRIs.
2022 Diagnostic Criteria for PSSD and related Sexual Dysfunctions published.
2022 Boston RCT shows Antidepressants not Depression leads to male infertility.
2022 PSSD network set up. For the first time, people put their names and faces to PSSD. The network starts engaging vigorously with Social Media.
2022. New York Times reports a growing number of American teens are on a growing number of psychotropic drugs – some on up to 10 meds.
2023 Spain, Italy, Japan, many European countries have Fertility rates below 1.30 Native Fertility Rates may be as low as 1.0 – in Britain women born outside the UK are having 30+% of babies.
2023 HCFEA in France reports that an increasing number of French young people are on psychotropic drugs. The response from psychiatry is this shows lots more children need help with SSRI and related drugs.
2023 Close to 30% of Spanish 18 year old girls are taking psychotropic drugs. Most countries report a huge increase in psychotropic intake among teens and children in recent years – commonly blamed on the Covid pandemic. This Spanish site links inequality in psychotropic drug intake to gender inequality.
2024 Nobody taking an SSRI is warned about Sexual Dysfunction or InFertility – the sexual and fertility effects of SSRIs are much more common than mood benefits.
2024 IVF rates approaching 10% in Scandinavia and Japan.
2024 Medical Assistance in Conception (MAiC) and Medical Assistance in Dying (MAiD) rates roughly equivalent in countries that have both.
2024 Emmanuel Macron launches a Demographic Rearmament campaign.
Between killing libido, and killing sperm, SSRIs may be the single biggest cause of infertility. They are increasingly an obstacle in the way of anyone wishing to remedy National Fertility Problems. This problem cannot be remedied if people are kept in the dark about these and other prescription drugs.
In his recent launch of a Demographic Rearmament program see Liberty, Equality, Fertility, aimed at supporting French Fertility, which seems to have taken inspiration from Salome Berlioux‘s La Peau des Pêches, Emmanuel Macron focused on making it financially possible for younger women or couples to have children. And also on the risks of Petrochemical – pertubateurs endocriniens – endocrine disrupting chemicals.
Fifty pages of the key report behind his press conference are given over to or mention these Petrochemicals, some of which are endocrine disrupting by accident.
One page mentions prescription drugs, medications sur ordonnance, which are endocrine disrupting by design.
Is this a bias to which we all succumb? We locate the dangers in life, the rapes, the abuse, the violence, in strangers – immigrants, chemicals we can’t see or recognize. But in fact again and again, the actual harm comes from familiars, people we know. The chemicals in shiny capsules we take every day that are given to us by the reassuring figure of a doctor.
RxISK knows of 18 people who have taken their own life with or without Medical Assistance because of PSSD in the last 2 years. There are likely many more.