This talk was given in Maastricht at the invitation of David Linden, Scientific Director of the Mental Health and Neuroscience Research Institute on November 27 and again to a group f Primary Care Doctors in Sweden at the invitation of André Marx on Nov 28. There were some great questions afterwards. This post gives the text of the talk along with the slides and links to related posts. There is a video of the talk below but so much more in the text including the outline of a new condition Narcissistic Doctor Disorder than in the live talk.
Slide 1. In 1958, Imipramine (in the middle above) was the first tricyclic antidepressant (TCA). By 1959, European psychiatrists, semi-Freudian mostly, agreed it could replace ECT in the treatment of melancholia. But even in these severely ill, often suicidal, patients, doctors could spot imipramine causing suicide. Doctors today can’t spot SSRIs causing suicidality in mild non-suicidal depressions. Why not?
Frank Ayd discovered Amitriptyline’s benefits in melancholia in 1959, which meant he wouldn’t have to continue giving his father ECT on the kitchen table. Melancholia kills libido and Ayd had no wish to create treatment hesitancy but he said amitriptyline caused a sexual dysfunction distinguishable from the effects of melancholia on sex. Doctors can’t now spot SSRIs causing even clearer sexual effects in patients with no prior libido problems. Why not?
By 1961 Julius Axelrod had established the 3 drugs on top here all inhibited norepinephrine reuptake, for which he won a Nobel Prize. This gave rise to Schildkraut’s Catecholamine Hypothesis, the original low neurotransmitter or chemical imbalance hypothesis.
Slide 2. Was melancholia a deficiency disorder like Parkinson’s disease? Would a pure norepinephrine reuptake inhibitor be more effective and free of terrible anticholinergic side effects? There was a snag. Benzodiazepines immediately did something clearly helpful. Ditto antipsychotics and stimulants. But tricyclics seemingly had lots of immediate side effects but no beneficial effect and catecholamine reuptake inhibition was immediate.
Slide 3. This is what melancholia, a disorder of middle or older years, looked like then. After 2 weeks treatment with ECT or TCAs it showed a response. But if there was no immediate and obvious drug effect, what was driving this? Did the drugs cure a lesion?
Slide 4. Fridolin Sulser’s catecholamine receptor hypothesis took over. These proteins might need chiseling for two weeks to come right. We now know receptors respond almost instantly but the weeks of chiseling notion legitimized the idea that TCAs took 2 weeks to correct a lesion. Like the Cheshire Cat, Sulser’s Receptors and then BDNF Biobabble left a Grin behind – we have to wait up to 6 weeks now for something to happen, even for much milder problems than melancholia, before people get well. In the meantime. they just have to put up with side effects.
Slide 5. I have over 100 interviews with early psychopharmacologists including Axelrod, Ayd, Kuhn, Schildkraut, Sulser and Carlsson. It costs over $1000 to buy the books these are in, but you can download all interviews for free from the Samizdathealth.org website, linked to Shipwreck of the Singular – See Shipwreck The Psychopharmacologists. Email me if you can’t find them.
Slide 6. All of the TCAs here except trimipramine inhibit norepinephrine reuptake. But in the 1960s psycho-analysts claimed Imipramine, Amitriptyline and Clomipramine had an impact on transference reactions which desipramine didn’t have. The impact was immediate.
Slide 7. Listening to this, Arvid Carlsson linked the changes in transference reactions to serotonin reuptake inhibition – desipramine doesn’t. He made a dedicated serotonin reuptake inhibitor to explore this further – Zelmid. This and later SSRIs mute sensory/emotional reactivity – they are Serenic – Anxiolytic.
Slide 8. Zelmid was not an anti-melancholic drug, it and later SSRIs are Serenics. But it became an antidepressant even though anxiolysis is where the money is because it was almost impossible at the time for a new anxiolytic to compete with benzodiazepines.
Slide 9. It was obvious 35 years ago that SSRI Marketing needed to shape-shift Valium cases into cases of Prozac, cases of anxiety into depression. Companies platformed doctors claiming depression lay behind many cases of anxiety and treating it would offer a real cure not a drug crutch – besides which antidepressants didn’t cause dependence.
Slide 10: For Carlsson SSRIs were a Therapeutic Principle that allow us to compensate for a problem. They were not Magic Bullets that fixed a lesion. Like LSD, working on a normal serotonin system, SSRIs could cause good and bad trips. Bad enough to cause suicide? Yes.
What’s a Therapeutic Principle? There are 4 kinds of constipation and 4 laxative principles. You can add fluid or bulk, stimulate or relax the gut. The wrong principle for your constipation can make things worse. But a company licensed to use the word Laxative would prefer you to be on 4 laxatives provided one is theirs rather than the right one for you. This way treatment resistant constipation lies.
Most medical problems from hypertension to type 2 diabetes, pain, and nervous problems have several potential therapeutic principles – getting it wrong can create treatment resistance. Euthanasia increasingly is the only way out of SSRI induced treatment resistance.
Slide 11. You might expect Therapeutic Principles for nervous problems to act on the brain, but benzodiazepines relax muscles, and beta-blockers slow heart rates, which fools our brains into thinking we are not anxious. But beta-blockers can increase heart rates for some creating anxiety. At this point we need someone who is working with us rather than from a book.
Slide 12. Therapeutic principles ask us to adjust a function to compensate for a lesion not correct it. Walter Hess, a 1949 Nobel Prize winner, directing his male students to think of functions asked them what their work could reveal about why they fell in love with a girl.
They were all guys back then. The girls were using anticholinergic drops to dilate their pupils which left guys thinking a girl liked them causing them to fall in love with her.
Slide 13. What function do SSRI work on? In 9 out of 10 of us, SSRIs cause genital numbing within 30 minutes of a first pill, at a fraction of the antidepressants dose. The degree of genital numbing correlates closely with reports of reduced emotional reactivity. Reduced sensory reactivity has face validity as a therapeutic principle in nervous disorders – and SSRIs work better for anxiety disorders than for depression and don’t work for melancholia.
Slide 14. In healthy volunteer trials, dizziness and balance effects are relatively immediate on starting and stopping SSRIs. These are not Side Effects. Balance and touch are sensory effects and show the core action of SSRIs are their sensory effects.
This slide shows balance problems reported to FDA on SSRIs. Only 1 in 100 get reported, so SSRIs have significant effects on our sense of balance for millions of us. PRRs (Proportional Reporting Rates) measure the rate this problem is reported compared to all problems on this drug balanced against the rate this problem is reported on all drugs compared to our drug. A PRR over 1.0 indicates a link, over 2.0 a strong link, and higher again points almost to certainty. These are stronger data than you get from RCTs.
Slide 15. Reports to FDA show visual issues on SSRIs in hundreds of thousands of us. There are less reports to FDA because ophthalmologists don’t report them as you’ll hear.
Slide 16. The idea that an action on sensory functions might be Serenic fits with the James-Lange Theory of the Emotions put forward in the 1880s which said our body senses/feels – it thinks fast – what we call emotions are cognitive interpretations/misinterpretations of these feelings.
Slide 17. For a century after 1832 when reflexes were first discovered. research established a series of gate controls up through the spinal cord enabling all animals, including us, to function without any mental or spiritual input.
These gates are topped out by a vigilance nucleus – the blue norepinephrine locus coeruleus and the green serotonergic raphe nucleus which damps down vigilance. The locus coeruleus needs the sensory hum to be gate-controlled in order to pick out salient actionable features. The serotonergic Raphe nucleus damps vigilance down. But we can empty out the 5% of serotonin in our brains, which is in the Raphe Nucleus, without causing problems.
Slide 18. I am only semi-saying we don’t need brains at all to work out what SSRIs are doing. I’m trying to get you to see us as more like Octopi than we normally see ourselves. In contrast to appearances, Octopi have Distributed Knowledge Centers in their arms – not in the bulbous head.
Slide 19. Acting on serotonin LSD opens our sensory gates, floods awareness, and overwhelms our heuristic – thinking fast – capabilities. The action on serotonin in humans was shown first in our gut. Very early on spiders, who like octopi have Knowledge Centers in their 8 legs and 8 eyes, given LSD wove weird webs.
Slide 20. SSRIs mute these sensory gates. This Brain Scan shows the effects of one dose of an SSRI in healthy volunteers – the sensory input from the body is diminished. Sensory Deprivation Tanks do something similar. This muting might seem to make interpretations easier but in practice muting can compromise our interpretations as you will see.
Slide 21. This quote gives you a sense of how sensorily deprived people can be.
The mental state is literally an altered state of consciousness that one absolutely cannot comprehend if he didn’t experience it. No words can explain such a thing. I am shocked such a state is even possible.
The best way to describe it is mental anesthesia. Everything in the mind is tuned down so low, even thoughts, emotions so muted they are barely relevant.
It’s the opposite of what psychedelics do. They enhance and amplify whereas SSRIs completely mute. One has the impression everything has been wiped out and there is no mind anymore.
Slide 22. Just as Cartoonists have known for decades about the biobabble doctors spout, they have also known for decades what SSRIs really do.
Slide 23. Some years ago in this unit we randomized 20 medical and nursing healthy volunteers to a norepinephrine reuptake inhibitor or an SSRI for 2 weeks, then crossed over to the other for 2 weeks. 48 hours into the study a patient asked me if Dr X, who he said was more mellow than usual, was on an SSRI. When we broke the blind – Dr X was on an SSRI. Patients are expert at observing people in a way healthcare staff no longer are.
The Grin of the Catecholamine Cat inhibits our ability to spot the obvious. Uninhibited patients, cartoonists and psychoanalysts see Good or Bad Trips within hours. Two of our volunteers became dangerously suicidal on the SSRI. Becoming suicidal on an SSRI is not a step on the way to an eventual Good Trip.
Slide 24. One of the main reasons why SSRIs go wrong is that worried SSRIs might not work in antidepressant licensing studies, as this graph shows companies dosed them at the toxic end of the dose range – 20 mg for Prozac. At 20 mg, a range of problems had to be covered with concurrent benzodiazepines. No trials show SSRIs working on their own.
Giving a benzo would not be a problem in cancer chemotherapy trial because we don’t expect Benzos to be anti-cancer. But using Benzos to damp down agitation in trials of a drug being brought to market to replace hazardous Benzos is perverse.
Looking at this dose response curve. you’d say a 5 mg dose would be optimal. After licensing Lilly published a 5mg Prozac trial. It worked better at a 5 mg dose. It’s lead author Lilly’s Joe Wernicke asked colleagues what do we tell people about this?
Again and again, when someone is not doing well on an SSRI, doctors increase the dose beyond 20 mg rather than lowering it.
Slide 25: Unlike LSD, which we take occasionally and recover from bad trips, we remain on SSRIs for months or years in toxic doses. Unsurprisingly, things break – sensory things break. PSSD (Post-SSRI Sexual Dysfunction), which can last for the rest of your life, points to the profound effects broken sensation can have – see PSSD Podcast .
Bryn: Getting PSSD undermines your faith in the whole system of science as we have it – its not some vague feeling. Losing your libido is equivalent to going blind or deaf, its that level of sensory impairment
Roy: The same can be said for losing your emotions – I felt I lost two senses – my sexuality and my emotions
Bryn: If we want to be believed we have to remember how incredible our story sounds … My Dad says its not possible a drug could cause these effects, it wouldn’t be on the market
Slide 26. A decade ago criteria for a new syndrome Persisting Postural Perceptual Dizziness (PPPD) were put on the map. This dizziness involves vestibular, visual and proprioceptive input – all of which have a serotonergic component. See Balancing our Bodies and our Selves.
Vertigo is a better word for this. For a tightrope walker vertigo would trigger a panic attack and panic is common in people with PPPD. Both starting and stopping an SSRI can cause PPPD and like PSSD or akathisia PPPD can endure for years. Vestibular Rehabilitation Therapy can help but while waiting folk get referred for trauma therapy and get given SSRIs.
This is not just a matter of negotiating things like climbing some steps, we live on a tightrope and our senses our emotions disturb our internal balance. Sensory disturbances like these strike at the very heart of us and fuel a turn to medical assistance in dying.
Slide 27. This fabulous image brings home a key point that disrupting embodied knowledge. as in VSS and PPPD has profound effects beyond just sensory issues. We’ve just published the largest series of cases of VSS linked to one drug group – SSRIs. Like PSSD, PPPD, VSS can start on starting or stopping SSRIs and can endure for years afterwards and people often figure they are going mad – especially with the response they get from health systems.
See Juggling Our Selves and Our Bodies.
Slide 28. Ophthalmologists and others looking into our eyes and not seeing a lesion, tell people this is a brain or mind problem – made easier to say of course if the person is on or has been on an SSRI. They may babble about thalamo-cortical dysrhythmia – a neuro equivalent to chemical imbalance. The patient gets referred for trauma therapy or has an SSRI recommended.
But comparatively speaking there is more serotonin in our eyes relative to their size than there is in our brains.
Slide 29. SSRIs achieve the effects we want by acting on our primary knowledge generators – our sensory systems. In the toxic doses prescribed they disrupt embodied knowledge. When this happens, patients complain about Brain Fog. They are certain their brains are broken but cognitive tests don’t show this.
When embodied knowledge breaks, we try to fix it by attending or concentrating more which is effortful and frustrating because that’s not the way to repair embodied knowledge – a complaint of Brain Fog almost proves the point.
Slide 30. Embodied knowledge gets made and repaired by blunt repetition. Trying to instruct bodies doesn’t work. The enduring sensory problems after SSRIs explain why withdrawal is so difficult. There is linked damage that does not go away with tapering.
Slide 31. In 1992, I chaired a UK launch meeting for Sertraline – Zoloft – for Pfizer. I told the audience serotonin was more primitive than estrogens or androgens and drugs acting on it would produce effects we had never seen before – good and bad. Science is about paying heed to new observations like these – even bad effects can open the door to new drugs.
You also need to know small molecules are promiscuous – they may have 100 effects. If you want precision you need a big, fat protein. Julius Axelrod who rediscovered acetaminophen – paracetamol, often said serotonin was a relic of our marine past. SSRIs act on something even more primitive than serotonin – they activate carbonic anhydrase enzymes – this produces fluid in confined spaces like our eyeballs giving us glaucoma.
Slide 32: This quote from Bruce Springsteen’s Born to Run captures sensory drivers behind his SSRI linked akathisia.
I was profoundly uncomfortable in my own skin. I just wanted OUT. It feels dangerous and brings plenty of unwanted thoughts. I couldn’t live like this…
I understood what drives people toward the abyss. There was no life here, just an endless irritating existential angst embedded in my bones. It was demanding answers I did not have.
Slide 33. Now adding weird new sensations that need interpreting to sensory muting opens a door, as this person hints, to dominant imagery and the consequences of that.
Just as my vision lost depth – it was more like a 2-dimensional videogame – there was a loss of depth to my thinking. I was reacting to things on the surface rather than able to see through to the consequences.
If I had an impulse to drive, I would go rather than consider the time or whether I had work the next day. If I had an impulse to go out for a walk, I might simply go without my phone – or shoes
Slide 34. Or this woman who ended up in an almost hypnotic state.
I was thinking I wanted to stop, that I didn’t want to do it, but I had to.
Why did you have do it?
Because I had started it – I can’t explain it.
Slide 35. I hope you can see we know what SSRIs do – they mute sensation. We know this from evidence going on them, coming off them, and from the functions they can break in us. Our right hand knows this. Our left hand doesn’t as you will see from Woody Witczak’s case. What happened to Woody has become the norm today.
This is Kim and Woody Witczak. He had just begun a dream job, they were happily married, thinking about a family, had booked trips. After a few nights poor sleep, Woody’s doctor gave him Zoloft. He became agitated. One minute he’d be fine, then lying on the floor saying Kim wouldn’t believe the thoughts he was having. Woody had a good doctor who said this was normal – SSRIs may not start working for 6 weeks. Hang in there. In the fifth week Woody hung himself.
If we are dealing with LSD, we don’t say this Bad Trip you are having will any moment flip over into a Good Trip. Why do we say it about SSRI Bad Trips?
The Grin of the Catecholamine Cat is partly to blame but there is another perverse source.
Slide 36. I’ve doctored the Great Seal of the United States. E Pluribus Unum – from many individuals, one people – now reads Mediocris – the Latin for Average.
Companies do Randomized Controlled Assays (RCAs) mislabeled as RCTs to get products licensed and claim these offer Gold Standard Science on what their drugs do. They brand Evident PSSD, VSS, PPPD, Suicidality or Homicidality as Anecdotes not Evidence.
Like Chat GPT or Grok, RCAs (even RCTs done by angels) are averaging machines. At best they allow us to say this drug is not totally without benefits, but they tell a doctor nothing about how to treat the person in front of them.
The averaging effect means SSRIs don’t differ much from placebos in the mild depression assays they were tested in. Averaging LSD trials would give the same outcome but no-one says this about LSD. The idea SSRIs are nothing more than placebos kills people.
Less than 50% of SSRI trials were positive but, with adverse SSRI effects damped down with benzodiazepines, a bunch of coding and statistical tricks and clear fraud, companies could pull out a result that allowed FDA at 6 weeks to license SSRIs as antidepressants.
These licensing linked maneuvers are the basis to the idea SSRIs may take 6 weeks to work. No lesion clears up. There is no evidence in these trials that a Bad SSRI Trip can finally morph into a Good Trip.
Based on 100,000 patients in company assays, FDA found less than 1 in 6 have a Good Trips on SSRIs. These 1 in 6 Good Trips allowed SSRIs to be licensed as antidepressants.
If companies had sought a license as a Serenic, the trials could have been as short as a week long and would have yielded a marked difference from placebo. Marketing got in the way of this. A Serenic license would have left too much to the discretion of doctors.
There is a further problem with RCTs. Not only do they average good and bad trips on one drug but if LSD and SSRIs and benzodiazepines and stimulants and antipsychotics were all put into trials of mild depressive disorders, although entirely different treatments doing completely different things, they would all end up looking the same – giving the same 3 points difference on a depression rating scale score.
I’m not sure we can blame FDA for this. The drugs have the capacity to work just like they have the capacity to cause suicide. Back around 1990, FDA may have expected doctors to work out how in practice to use these drugs to better effect than company assays suggested.
Slide 37. RCAs allow companies to create a Wonderland. The label attached to their drug acts like the labels Alice faced in Wonderland where food and drink were labeled Eat Me and Drink Me leaving her incapable of not doing this. FDA labels have this effect on sophisticated women who won’t take soft cheeses, or processed meats but consume prescribed SSRIs in ever greater quantities when pregnant.
Freudians who spotted serotonergic impacts on transference reactions can explain what’s going on. Companies have nudged doctors and an educated elite into Delegating Narcissism to FDA .
Slide 38. Mark Anthony said he came to Bury Caesar not to Praise Him. I thought about starting this talk with I’ve come to Praise SSRIs not to Bury Them. SSRIs work – it’s doctors who are not working.
The hazards you’ve heard about may leave you figuring we need to bury SSRIs. Listen up. Unless we realize how valuable a scientific and therapeutic tool SSRIs can be, Doctors risk being Buried.
Slide 39. The Federal Aviation Authority (FAA) licenses planes the way FDA licenses drugs – by looking over paperwork. FAA don’t keep you safe in the air – pilots do. They have an incentive – if you don’t get to New York, they don’t either.
Doctors are health pilots, not FDA. But if the door flies off a healthcare plane and you draw attention to this the incentives tell doctors to throw you through the opening for spreading Treatment Hesitancy.
Slide 40. This is an inevitable consequence of Doctors Delegating Narcissism to bureaucrats. Journalists researching adverse events hear doctors telling them people claiming to know they have PSSD, for instance, have Narcissistic Personality Disorders.
When growing up, we Delegate our Narcissism to father figures. Later when confused we may delegate it to dictators, or gurus. Delegating it to bureaucrats suggests extreme vulnerability. Managing Treatment Hesitancy for life-saving treatments is one thing but as Goldman Sachs have told us, making drugs that save lives is a bad business model – the pressure to push down the price of life-saving drugs is huge. Companies make cosmetic or identity disorders to sell profitable drugs, using doctors who they view as devoid of a thought in their heads not put there by them as the front of house sales force.
We are not dealing with a Big Pharma making life-saving drugs, but with Big Propaganda, whose propaganda has become invisible. Behind EBM and Follow the Science labels, and a chorus line of Narcissistic Disordered Doctors, singing Let’s Do the Narcissistic Tango Again we no longer see this.
If their defenses are challenged, as doctor’s are when someone turns up with very Evident adverse effects, narcissists get aggressive and pick on victims. This system breeds violence. Clinical psychologists seeing the same patients as doctors are mostly too scared to hint that obvious side effects are treatment related for fear of a threatening email or worse from a Medic telling they are not licensed to practice medicine. This isn’t just bad healthcare – it flies in the face of Science.
A note of caution is needed here. I am not talking about Bad People. I am talking about a Bad System. You may need to be as close to the pharmaceutical industry as I’ve been to see how the System works.
Slide 41. In The Antidepressant Era 30 years ago, I offered a thought experiment. What if these drugs were over the counter (OTC) rather than prescription only. This wasn’t a policy proposal. I was drawing attention to the fact that since 1962, to give you Prozac FDA regulations require me to give you Depression. I need to disable you. If I do this, we have to be sure we are going to bring good out of this injury.
Switching to OTC bears thinking about as a policy proposal now. The molecule on the left is a potent SSRI that can cause all the problems SSRIs cause but if Woody Witczak had taken it and not Zoloft he would be alive today. Why? Because chlorpheniramine is OTC, and if it didn’t suit Woody, uninhibited by a good doctor, he’d have stopped it. Do doctors add value here?
If our drugs work as well as we are told and are as free of problems, doctors aren’t needed. Nurses and pharmacists are cheaper prescribers and maybe safer than a narcissistically challenged doctor. Doctors deserve to be and are rapidly being buried.
In The Antidepressant Era I also said that if these drugs were OTC companies would ensure all of us – not just doctors – wouldn’t have a thought in our heads not put there by them. The use of Tylenol in Pregnancy, is a great example of this.
Hims and Hers, and other platforms, now sell prescription drugs OTC – see Authenticity Inc. Telehealth and Influencers. The Creation of Psychopharmacology 25 years ago spelt out how companies like this would ambush us. They use instruments, like rating scales, blood tests or bone scanners, to create figures which their drugs can put right for us.
Slide 42. Checking the figures for our weight began in France in the 1860s. A decade later a new disorder was born – anorexia nervosa. Fasting had been a way to holiness, but became a health and beauty matter. Figures can hypnotize us as easily as icons or incense can.
Companies now create Food Noise scales – See Authenticity Inc – designed to show Glyp-1 agonists muting distracting food noise.
Social Media is full of Apps generating figures, Treating figures gives the appearance of science rather than the appearance of a Neurotic Disorder.
Weighing scales and rating scales hypnotizes us. Scans and blood tests hypnotize doctors.
Slide 43. Here are rarely seen figures for rates of starting SSRIs among Australian women. The Green line shows figures for women in the 45-54 age bracket who are representative of all older women. The red line shows the rate for 18-24 year olds and the blue line is for 10-17 year olds. In 1990, Antidepressants were rarely prescribed other than to people of middle years but driven by social media they are rapidly becoming drugs for younger folk.
The prevalence of SSRI use for middle aged women is 4 times higher than the incidence figures – breaking up with SSRIs is hard to do – and so prevalence increases with age. The prevalence for 10-24 year olds can never catch up because unlike Peter Pan they do grow up – even so prevalence rates in this age group are rising faster than for any other age – up 110%.
These incidence figures above are for prescribed drugs. How would they look with Hims and Hers online supplies added?
Slide 44. The gray line is for suicide rates among 15-24 year old males over the last decade. They are 4 times higher than the blue female 15-24 year old rates but both are rising at the same rate. And we now have the first legal cases for suicides after contact with Hims and Hers – Authenticity Inc Meets Grok.
Slide 45. The blue line shows the most solid finding in all of the social sciences – 600 studies showing unhappiness with life is most marked in the 40-60 age bracket and until 2018 least marked in under 24 and over 64s.
But the redline shows a dramatic shift – unhappiness is now most marked among 18-40 year olds. Are these canaries telling us this mine is about to collapse?
We now have a social welfare crisis with this generation branded Generation Sicknote and talk of countries collapsing beneath the burden of disability payments – See The Great Silence and Damsels in Distress.
Slide 46. Science began in London in 1660, when a bunch of men began holding events at which they did things like transfused the blood of a young dog into an old dog and observed – it seemed invigorated. Or looked down a microscope to see what they called microbes – were these animals?
These Events produced Observables about which the witnesses, like a jury, were challenged to come to a consensus. Science like a legal trial is an experimental process – it is not something to be followed. It is not a religion – See Health, Care and Science in the Real World.
A Case Report was made for the event and its consensus. No industry or regulators branded these as Anecdotes. This anecdotal process put men on the moon, decoded the human genome and extended life expectancies.
Medical journals came 200 years later. RCTs and their statistics 300 years later. The 1950s was the stellar decade for drug discovery when almost all classes of medicine we have now came into being. None of these breakthroughs involved RCTs. Many of these drugs, like imipramine, which people could see in real life had the capacity to work even if they also had the capacity to cause bad trips, remain better than later treatments. Life expectancies have been falling since the introduction of RCAs – especially in the United States.
There are no observables with an RCT. There are figures but figures are not observables, least of all when processed through statistical models. People are the data and especially with RCAs no person (or their ghost) entered into the study can be brought into Court to be examined and cross-examined.
You are not going to hear that this man with an improving Depression score, who dropped out of a Zoloft trial coded as nausea, was in fact Homicidal and Suicidal. Or a man, whose death was coded as burns, was so agitated he poured gasoline on himself and set fire to it intending to commit suicide.
No ‘investigators’ listed on the authorship lines of these ghostwritten (or AI generated) papers can be brought into court to testify because none of them have seen a person given this drug.
None of this is Scientific Evidence. It’s Hearsay.
In contrast, every time we prescribe a drug to someone we initiate an experiment that takes place in front of us or can do if the observers make it possible to observe what is happening – see below.
When we prescribe any medicine we open a door to the purist form of science there is and with SSRIs we have a tool with which to explore some of the most fascinating issues imaginable.
Slide 47. Before engaging in pure science, this scarecrow, as in The Wizard of Oz, needs a brain, a heart and courage, given to him by an ordinary girl, who may have dilated her pupils to fool him into thinking she thinks he’s amazing. Of course the uniform needs to be removed.
He’s supposed to be a professional. That means he puts you and what you need before Church or State, the guideline issuing folk, who want him to get you to conform to what they want you to be.
Rarely in the course of human history have such a small group of people held so much power over the lives of so many as doctors have with prescription-only meds. It’s extraordinary that we doctors find ourselves in such a weak position today.
Doing science means having people with different points of view in the room willing to observe and come to a consensus. It means recognizing the person who takes the pill has a privileged position on the observables, as do family and friends.
Becoming suicidal on an SSRI or having other strange experiences on this or other medicines poses a huge challenge to the scientific enterprise – those with a privileged position to observe what is happening will often be understandable wary of telling others much if anything about the thoughts now going through their head, Woody Witczak did not tell Kim that his thoughts included killing her.
Psychologists are important as we are talking about using drugs to shape behavior not cure a defect. Social workers and others count because context is important, and the pill-taker may need rescuing from a doctor hypnotized by figures abstracted from a bigger picture. These others are important because of their bias – not because they have no bias. You should only let yourself be treated by a doctor who is not just open to other voices but actively engages them – especially yours.
Exploring how SSRIs might help needs sophistication – that is an ability to hold contradictory or ambiguous details in mind at the same time and still function.
There are at least 3 steps to better therapeutic outcomes wins with SSRIs.
- Reducing the dose to at most a quarter of the usual dose, or less – the equivalent of 2-5 mg of fluoxetine, would give a better than the 1 in 6 Good Trips found in company trials.
- Doctors specifying what they want an SSRI to do to help a person – they cannot say they will get you well. They have to specify the step on the way to helping, just as with a beta-blocker we would say this will slow your heart rate and ease any shake in your hand or voice or with a benzo we would say this will relax your muscles.
- Recognize that what we call SSRI side effects are often the core action of the drug and not a side effect – they are adverse effects because the usual starting dose for SSRIs is at toxic levels.
- Getting the person taking the meds to interocept the sensory changes that start within an hour of the first dose. This may enable him/her to titrate what is happening to the right level for them or stop a treatment if need be.
Up the 1980s medicine centered on the problems people brought us. By 1990 we were bringing people into our clinics to screen them for risk factors etc and essentially were giving them problems they didn’t know they had and often adding in treatments they didn’t need.
When a person brings an ‘adverse event’ to us – this is traditional medicine. They are bringing us real problem and need traditional medical wisdom and relationships.
Beyond therapy, the boundaries of science need pushing forward. Good Science is not a matter of knowing research methods and applying for big money grants. For a doctor doing science can pay for itself – you get to trade 100 heartsink patients for 100 free research assistants whose skin in the game is a better qualification for meaningful input than university qualifications.
For psychiatrists who want to remain in the one true faith, this approach offers the chance to follow in the footsteps of Emil Kraepelin no less who with Wilhelm Wundt in the 1880s created Pharmacopsychology. Using caffeine, alcohol, cocaine and opioids then, it seemed obvious to Kraepelin and Wundt we had new tools to investigate who we are.
Kraepelin would have died for access to an SSRI. Our subjectivity, no less, is up for exploration and SSRIs on one side and LSD on the other offer wonderful tools to explore it.
But instead for the last 150 years this science has been ignored. Never in the history of science have so many observations by so many people been jettisoned by so few – and things are getting worse.
One reason why the sensory impacts of SSRIs have been ignored is that the science of the sensory nervous system has been seen as too subjective – especially by neurologists, who like the reliability of tests for the peripheral motor system and increasingly brain scans, but steer clear of a system whose responses can change from moment to moment and with both time of day and time of the month, and can vary hugely by personality type and emotional state. The only tests in common use for the sensory nervous system are biopsies to count the number of nerve endings in skin and even these correlate poorly with what people report.
Catatonia is among the most fascinating subjective mysteries. It lies on the boundary between voluntary and involuntary actions, between assigning responsibility or deciding it doesn’t apply. LSD can trigger catatonia. SSRIs can relieve it.
Hypnosis is another state. SSRIs facilitate it. What does that tell us?
Toxic doses of SSRIs can leave sexual. balance and visual problems in their wake. A genetic variation in PIEZO2 proteins causes sexual, balance and vision problems. PIEZO proteins (1 and 2) are sensory receptors whose existence we stumbled on just over 10 years ago. What other elements of our sensory system are out there waiting to be found? Humility rather than arrogance should be our default mode.
Before SSRIs and Viagra, male impotence or premature ejaculation were viewed as anxiety based neuroses needing months or years of damaging therapy dissecting personalities and histories. Lidocaine gel made penises less reactive before SSRIs – what does lidocaine say about the degree of brain involvement in Serenic effects?
How many other states might be helped by a judicious use of drugs to shape behavior rather than correct a disease?
Women disabled by dyspareunia face all kinds of protracted therapies aimed at rooting out their problems. Changing partners can solve dyspareunia (and premature ejaculation). We get told that’s because the new partner is more sensitive. Do we know for sure that’s the case?
In a group of couples, try asking how many women think they could only marry a man with the right smell? Chances are half the women will instantly endorse the idea with others looking flummoxed. What happens when your partner tells you your smell has changed since you began that drug? What happens if she develops parosmia on an SSRI – that might endure for years after stopping?
How much do we know about Material Me or about Material Us?
As Mark Anthony might have said:
The evil that wonder drugs do lives on after them –
the good is oft interred with their bones
These earlier posts touch on similar themes:
- Who’s Afraid of Science
- Healthcare Gone Mad
- Probity Blockers and Trans Medicine
- Health Care and Science in Real Life
- Die RxISKing it
- Die RxISKing it 2
The notion of Interoception comes up in the talk. The posts below deal with this in more detail.
The Science of Interoception – forthcoming
Pharmacopsychology – forthcoming
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