That Let Down Feeling

Antidepressants strike again

These posts examine modern psychiatry from a critical point of view. Unfortunately, mainstream psychiatrists usually react badly to any sort of critical analysis of their activities, labelling critics as “anti-psychiatry,” whatever that is. Regardless, criticism is an integral part of any scientific field and psychiatry is no different. As it emerges, there is a lot to be critical about.

If you like what you read, please click the “like” button at the bottom of the text, it helps spread the posts to new readers. If you want to comment, please use the link at the end rather than email me as they get lost and nobody sees them.

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“Those who cannot remember the past are condemned to repeat it.”

So said the philosopher, George Santayana in 1905, although it seems that ever since, humans have been determined to prove him wrong but have failed at every attempt. History is incredibly important, and that’s even more true of psychiatry as its subject matter is so vague and ill-defined compared with other fields. Trouble is, psychiatry’s history is so bad that nobody wants to look at it which is a pity because it shows one persisting feature: that in its desperation to come up with successful treatments, new treatments are introduced long before the technology to investigate them even exists.

Look no further than convulsive treatments, introduced in the 1920s by a young Hungarian pathologist (that’s correct), Ladislas Meduna (1896-1964). Meduna noticed that the brains of people who died with chronic epilepsy showed widespread microscopic scarring (gliosis), which didn’t happen to people dying after long-term schizophrenia. Within mental hospitals, it was widely believed that epilepsy somehow protected against schizophrenia, so Meduna wondered whether inducing fits in people with chronic schizophrenia would cause diffuse, low grade brain damage and thus relieve their symptoms. He experimented with injecting various nasty chemicals before choosing a camphor-based drug which caused a sense of mounting terror in the patients lasting up to half an hour before they had series of fits. The response was unpredictable but it seemed to work on catatonia, so his novel treatment spread quickly. They had no idea how it worked and certainly didn’t bother with any modern niceties such as informed consent. The important point is that it was done with the specific intent of inducing significant brain damage.

Encouraged by this, an Austrian psychiatrist, Manfred Sakel (1900-1957) decided to cause fits using insulin, which had recently been isolated. Overdose with insulin causes seizures due to low blood sugar, which could be reversed by giving a sugar drink through a nasogastric tube. This seemed to work better and became widespread in the US, UK and other countries. However, it was very demanding of staff time, so a small group of patients ended up getting 80% of all the staff attention while the rest simply sat in despair in the back wards. Again, nobody had a clue how it worked. In 1939, Dr Ian Skottowe, an influential British psychiatrist, published a paper in the prestigious journal, Proceedings of the Royal Society of Medicine, which proposed that insulin shock worked by stimulating injured neurons to take up excess sugar [1]. Or something, it is actually gibberish but it would have been impressive at the time. Fifteen years later, insulin coma therapy was found to be useless; any improvements were due to the extra attention the patients were given [2]. The young registrar who worked that out was made to suffer for the rest of his career.

The prize for blind poking must surely go to what is laughingly called “psychosurgery,” cutting the brain to relieve mental symptoms. This was developed by a Portuguese neurologist, Antonio Egas Moniz (1874-1955), who made his name when he developed the radiological technique of cerebral angiography. In this procedure, a contrast medium is injected into the carotid artery before taking a series of Xrays of the head, which shows the blood flow in the brain and any distortions caused by tumours, etc. It was widely used until CTs became available, but still has a place. In about 1935, Moniz went to a lecture at a neurology conference where somebody described how they had changed the behaviour of some chimps but cutting parts of their brains. He wondered whether it would work on aggressive mental patients. When he got home, he convinced a colleague who ran a mental hospital to lend him some patients to try it on. It was a disaster but they pressed on. Soon, the idea spread to the US where it was pushed with evangelical zeal by seriously unbalanced psychiatrist Walter Freeman, who championed the idea that all severe mental disorder could be cured by shoving a large-bore needle up into the skull through the conjunctival sac, above the eye, and wiggling it around. Over the next twenty years or so, even though it was entirely lacking any valid scientific basis, perhaps 75,000 people in a dozen countries were subjected to this procedure. Anne Harrington’s account of the history of “lobotomy” is simply chilling [3].

Everything changed in the early 1950s when research on antihistamines yielded drugs that produced a state similar to that seen after a Freeman-style attack on the brain. Patients became apathetic, inert and detached, with very little emotion or interest, i.e. a “chemical lobotomy.” The first, chlorpromazine, was quickly adopted; others followed soon after, transforming mental hospital psychiatry but nobody was much concerned about side effects, including weight gain. It’s often said that these drugs led to the closure of the huge Victorian mental asylums but that process was already under way before the drugs arrived. Before long, some of the drugs seemed to be more effective in depression so they were labelled “antidepressants” and, from about 1960, took off.

Starting in the late 1960s, pharmacologists searched for drugs that would be more specific for the neurotransmitter serotonin (5-HT) because this seemed to have more involvement in emotions and less in motor systems. They started with the antihistamine diphenhydramine and, for the first time, deliberately altered the chemical structure in order to find a more specific drug. This took years but, in 1974, they found one that wasn’t too toxic, fluoxetine, the first SSRI. It was authorised in 1987 and, marketed as Prozac, has had a huge effect, as well as making untold billions for the company. Copycat drugs quickly appeared and now about 15% of the adult population in English-speaking countries take antidepressants. Years later, the side effects are much clearer, and far worse than the drug companies let on [4].

All drugs have side effects, that’s inevitable, but drugs used in psychiatry are worse than most. They are unusual in that some side effects take years to develop, others don’t wear off when the drugs are stopped while some don’t become apparent until the drugs are stopped (called withdrawal everywhere else). Now, nearly 40 years after the SSRIs were released, psychiatry is reluctantly accepting that some of these symptoms are real, disabling and untreatable. They aren’t due to “the mental illness coming back again,” the usual excuse given to resume the drug. The weight gain and emotional numbing tend to wear off soon after the drug is stopped but others are very persistent, perhaps even lifelong. One of the most distressing is the loss of sexual libido and performance, which now has its own name, Post-SSRI Sexual Dysfunction, PSSD [5] (recent video here).

As soon as the drugs are started, people will complain (if they’re allowed to) that they lose their sexual interest and ability to function. They describe genital numbing, loss of arousal, and failed orgasm, with dryness in women and impotence and ejaculatory failure in men. This is very troublesome and will persist as long as the drug is taken. It’s a major factor in why 40% of people stop these drugs within the first year. However, all too often, life never returns to normal [6]. Why wasn’t this publicised from the beginning? For the same reason SSRI-induced suicidal ideas were suppressed: nobody would take the drugs if they knew the facts [4].

Recent research has shown that SSRI drugs are not selective at all. They have major effects on brain systems that, as far as I can tell, weren’t even known in the 1970s, neurosteroidogenesis. The group of steroid hormones, which derive from the cholesterol molecule, are of immense importance in the body. Sexual hormones belong to the steroid class but it is now clear that they are also produced within the brain itself, by neurons adapted for this purpose in a number of deep brain structures. Just what they do isn’t yet clear but their importance is well-known: they act directly on the brain in sexual and emotional behaviour. Trouble is, they can’t be studied by blood tests or even by analysis of cerebro-spinal fluid as the amounts involved in brain tissue are almost immeasurably small and are swamped by the same chemicals produced outside the brain.

The technology involved in studying these chemicals is remarkable; it relies on genetic and immune analysis which wasn’t available until about 20 years ago. In a study in rats, a research group in Milan has found that the common SSRI paroxetine rapidly blocks the secretion of these hormones in the brain, at the same time as the animals show major loss of sexual interest and activity [6]. However, when the drug is stopped, the changes don’t reverse. The blockade in the production of these essential hormones develops quickly but it appears to be long-lasting, if not permanent, due to changes at the chromosomal level. The actual DNA sequence doesn’t change but its expression is impaired by structural changes such as, for example, when one section of the chromosome links to another as a drug effect. Thus, the DNA can’t be “read” by the messenger RNA molecules as the first step in the production of the hormones. It’s as if the pages of a workshop manual or a recipe book have been stuck together so nothing can be read. These are known as epigenetic effects and, because neurons last a long time, once induced, these changes are probably permanent.

The principle known as “informed consent” says that people have an inalienable right to know the potential benefits and the “significant” risks of any treatment, and practitioners have a compelling duty to give that information in a comprehensible form, therefore everybody should be given in writing a list of side effects. I did this as a routine. The effect was that about 95% of people refused them, so I commenced antidepressant drugs in no more than about 2% of new cases, most of whom had had them before and wanted them again. Patients with no experience of them weren’t prepared to run the risk of major weight gain, loss of sexual function, akathisia, drowsiness and lethargy, lack of energy, low motivation, impaired coordination, acute mania, dulled emotions and, of course, sudden suicidal ideas. It means more work for the psychiatrist but people are entitled to weigh up the risks and benefits and make their choice. They got better anyway.

Forty years ago, none of the physiology of epigenetics was known. Now, large numbers of people around the world from as young as twenty find that after a course of psychiatric drugs, especially the SSRIs, they are essentially neutered, with no foreseeable prospects of recovery. A group in the UK, PSSD Network, are working to publicise what is yet another in a long line of psychiatric disasters. The cause is always the same: psychiatrists are ideologically committed to finding a “physical” or brain-based cause for mental problems, and leap at anything that seems to give them what they want, long before they have any idea of what is actually involved. The human brain is the most complex thing in the known universe. It requires an entirely different mindset to the standard approach in physical medicine. They are blinded by their slogan that “mental disorder is brain disorder,” unable to see that the complexity of the human brain is light years removed from their crude, linear thinking.

When we line up all the tragic messes psychiatry has dished up, even just over the past eighty years [7], it’s time to call a halt. All the high-sounding talk of neurotransmitters and brain circuits and deep brain stimulation and so on is just pseudoscience, same as Skottowe’s made up stuff 90 years ago (he also advocated Deep Sleep, and a combination of amphetamines and opiates for depression; see his obituary from 1984). None of this talk, either in the 1930s or now, is based in even the slightest understanding of how brain and mind interact. These drugs are a success story in marketing, not in pharmacology, nor in practical psychiatry. They’re sold on the spurious basis that depression is common, life-long and very serious, not on the basis of their side effects or their actual efficacy. They’re supposed to “relieve depression and prevent suicide”? Well, they’re not working. Around the world, as the rate of prescription of these drugs rises, so too does the suicide rate [8]. All too often, desperate people use the antidepressants themselves to end their lives. That bit, however, is kept very quiet, along with the fact that nobody actually knows what they do in the brain. Scary, but that’s free enterprise for you.

References:

1. Skottowe, I (1939). Shock Therapy: A Plea for Proportion in Psychiatry. Proceedings of the Royal Society of Medicine. 32:843-852.

2. Bourne, H. (1953). The insulin myth. Lancet. ii. (Nov 7 ) 265 (6798): 964–8.

3. Harrington A (2020). Mind Fixers: Psychiatry’s Troubled Search for the Biology of Mental Illness. New York: Norton.

4. Aboustate N et al (2025). Restoring TADS: RIAT reanalysis of the Treatment for Adolescents with Depression Study. Int J Risk Saf Med. N/S, p1-20. DOI: 10.1177/09246479251337879

5. Healy D (2020). Antidepressants and sexual dysfunction: a history. J Roy Soc Med, 113(4): 133–135. doi: 10.1177/0141076819899299

6. Giatti S et al (2021). Effects of paroxetine treatment and its withdrawal on neurosteroidogenesis. Psychoneuroendocrinology. 132: 105364. https://doi.org/10.1016/j.psyneuen.2021.105364

7. Scull A (2022) Desperate Remedies: Psychiatry and the mysteries of mental illness. London: Penguin.

8. Amendola A, Plöderl M, Hengartner MP (2024). Suicide Rates and Prescription of Antidepressants: Trends in the United States, 1999–2020, by Sex and Race/Ethnicity. J Crisis Intervention & Suicide Prevention. On line, February 14, 2024. https://dx.doi.org/10.1027/0227-5910/a000941

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My critical works are best approached in this order:

The case against mainstream psychiatry:

McLaren N (2024). Theories in Psychiatry: building a post-positivist psychiatry. Ann Arbor, MI: Future Psychiatry Press. Amazon (this also covers a range of modern philosophers, showing that their work cannot be extended to account for mental disorder).

Development and justification of the biocognitive model:

McLaren N (2021): Natural Dualism and Mental Disorder: The biocognitive model for psychiatry. London, Routledge. At Amazon.

Clinical application of the biocognitive model:

McLaren N (2018). Anxiety: The Inside Story. Ann Arbor, MI: Future Psychiatry Press. At Amazon.

Testing the biocognitive model in an unrelated field:

McLaren N (2023): Narcisso-Fascism: The psychopathology of right wing extremism. Ann Arbor, MI: Future Psychiatry Press. At Amazon.

The whole of this work is copyright but may be copied or retransmitted provided the author is acknowledged.