The drug industry adapts to changing circumstances.
For no particular reason, the Guardian recently carried an article on withdrawal from antidepressants with the reassuring title: “‘I stopped sleeping’: the sometimes difficult path off antidepressants” Guardian, 23.04.17:. The author’s reality wasn’t quite so reassuring:
Six weeks after my doctor advised me to stop taking the lowest dose of desvenlafaxine, an antidepressant I had used for seven years, I returned to my GP. I was having huge mood swings: one minute I’d be so jittery and hyperactive I felt as if I could jump out of my skin, the next I’d be sobbing hysterically, convinced that life was hopeless. My stomach churned with nausea and bright light burned my eyes. Worst of all were the “brain zaps”, a deeply unpleasant buzzing pulse that shot through my skull at random.
The article explains that one Australian adult in seven takes antidepressants, often for many years, which is one of the highest rates in the world. However, it would appear that after stopping the drug, the reporter got off fairly lightly. People report a wide range of effects including all the above, plus twitches and jerks in the limbs, peculiar electrical tinglings anywhere in the body, headaches, poor memory, difficulty thinking or concentrating, a range of sexual side effects and, above all, severe irritability, for as long as two years. However, her GP wasn’t convinced it was a drug effect:
My doctor told me it was unlikely these symptoms were being caused by withdrawal from the drug … because it was out of my system …
That’s a bit strange because the definition of a withdrawal effect is what you get when the drug is out of your system. Clearly, the GP somehow thought “drug side effects” and “drug withdrawal effects” are one and the same thing, and nothing much to worry about. She was advised she could either put up with it or resume the drug, so she decided to look into it a bit more. This is also rather surprising because when it comes to the drug industry, reporters lick their pencils and diligently copy every word told them – by the drug industry.
However, the first person she asked was the well-known authority on all things psychiatric, Prof. Ian Hickie. Hickie told her that antidepressants work by changing the synapse, the connections between neurons, “So six weeks is a short period of time in terms of the rearrangement of the circuits that happen as a consequence of taking the drug away.” Two surprises here, the first being that he obviously hadn’t been listening to his good friend, the President of the UK Royal College of Psychiatrists who provoked a row a few years ago when she announced, on no evidence at all, that withdrawal effects from antidepressants are minor and rarely last more than two weeks. She was immediately challenged by the Critical Psychiatry Network in the UK and, after a fairly nasty row, was forced to back down. Unfortunately, the new withdrawal guidelines issued by the RCPsych are vague and wishy-washy and give no practical advice while playing down withdrawal effects. They also manage to say that being dependent on psychiatric drugs “… is not quite the same as being addicted.”
The second surprise is how quickly Hickie has adapted to the study by Joanna Moncrieff and colleagues, published July 2022 [1], which more or less killed the trope that “antidepressants correct a chemical imbalance of the brain.” Here we have Hickie announcing that antidepressants work by changing the connections between neurons so if you stop the drug, you will experience a “… rearrangement of the circuits that happen as a consequence of taking the drug away.” That’s a polite way of saying “drug withdrawal effect” and that it will last much longer than six weeks. Of course, nobody knows anything about alleged “brain circuits” involved in the experience of depression but that’s the new buzz phrase that has replaced “chemical imbalance.”
In fact, Hickie is just copying the former director of the US National Institute for Mental Health (NIMH), Thomas Insel, who announced in 2010 that NIMH was dumping “chemical imbalances.” He proposed a new framework of research in mental disorder which “… conceptualizes mental illnesses as brain disorders … (which) can be addressed as disorders of brain circuits”. Insel and Co. believed that the circuits could be studied using the usual laboratory tools of neuroscience, leading to a full understanding of mental disorder with no questions unanswered. Insel, it should be remembered, trained as a psychiatrist many years ago but spent practically his whole career in neuroscience laboratories. His reputation was built on research on the brains of voles. In any event, despite spending billions of taxpayers’ money on basic biological research, he admitted in 2017:
I spent 13yrs at NIMH really pushing on the neuroscience and genetics of mental disorders, and when I look back on that, I realise that while I think I succeeded at getting lots of really cool papers published by cool scientists at fairly large costs – I think $20billion – I don’t think we moved the needle in reducing suicide, reducing hospitalisations, improving recovery for the tens of millions of people who have mental illness. I hold myself accountable for that.
Nice of him to admit it, especially when he had set NIMH on its grimly biological path, then left to work for Google. So Hickie was apparently unaware of Insel’s realisation that brain circuits weren’t the way to go, as I had warned in 2011 [2]. Still curious, the Guardian’s intrepid reporter continued:
Antidepressants … are a critical intervention for millions of people experiencing the debilitation of depression, and can be life-saving.
The surprises keep coming, because the one thing we certainly do know about antidepressants is that as the consumption of these drugs has risen steadily (from 1% of adults in this country in 1990 to about 14% today), so too has the rate of suicide and the rates of people on disability pensions for depression. Bob Whitaker has given these figures in graphic form in a recent post on Mad In America, which I recommend. This would appear to be a classic example of what the author Kingsley Amis had in mind when he pronounced “More means worse.” The more drugs people take, the worse the outcome. In fact, The Economist (Too many people take too many pills paywall) this week carried an article on polypharmacy in the elderly, warning that perhaps it wasn’t such a great idea after all. So it’s interesting to see that Insel’s crusade to turn psychiatry into a biological science is bearing some fruit, if not quite the ones Hickie was hoping for, but first, a quote from an expert. The remarkable American comic, Groucho Marx, said: “Sincerity is everything in business. If you can fake that, you’re made.”
A report in the drug-company financed newsletter, Psychiatric Times, announced that the “unmet need” of a drug to control agitation in Alzheimer’s Dementia (AD) is moving through the testing and approval process: “If approved, (brexpiprazole) will be the first FDA-approved treatment for agitation associated with Alzheimer dementia in the United States.” This drug is derived from the antipsychotic aripiprazole, essentially what is called a “me-too” drug, meaning the manufacturers have tweaked the molecule a bit to get a new patent.
With what they call the “rapidly-ageing baby boomer population,” the numbers of sufferers in the US will swell from about 6million now to 13million by 2050 (I’ve never understood that expression; as a card-carrying boomer, called a Seniors Card here, I’m ageing at about the same rate as I always have, roughly one year every twelve months, but that’s statistics for you). Assuming one Alzheimer’s patient in four is deemed agitated, that’s a pretty substantial market. Of course, if the drug becomes available, that number will double overnight because that’s the effect drugs have on symptoms: if you find a cure, a disease will develop to use it.
The cost of brexpiprazole in the US is currently US$1,504 per script of 30 tablets, barely a month’s supply. That’s US$18,000 a year, so for 1.5m patients, we’re looking at serious money, say US$27billion a year in sales for “the first drug for agitation in AD.” Now that’s a bit strange because I recall from the early 1970s that, in pericyazine, we had a very good drug for agitation and/or aggression in brain-damaged and dementing patients. Pericyazine is related to the phenothiazine antipsychotics and was discovered in about 1960 but it was quite weak so it was rarely used for psychosis. However, being weak meant it was ideal for the elderly. They started on 3 tablets a day, and after a week or so, it could be reduced to two a day, and eventually to one, with minimal side effects. Apart from the fact that granny was a lot more settled and cheerful, relatives could usually not tell she was taking it.
The cost of pericyazine in Australia varies a bit but it’s about $25 for 100 tablets, a month’s supply or more. Oddly enough, it’s available in just about every country in the world but it isn’t approved for sale in the US. That’s because no drug company has applied to the FDA to list it. So they don’t approve the cheap drug that works but they are thrilled to approve an outrageously expensive drug, just as long as Medicare US pays for it. Oh, and side effects of brexpiprazole include akathisia (severe agitation), weight gain and “impaired impulse control” (usually known as aggression).
So one thing is critical, which goes back to Bro. Groucho’s comment above: In that bastion of free enterprise and sincere antisocialism, if you can get the government to pay for your product, you’re made. Unless the manufacturers can convince Medicare US to pay for brexpiprazole, it won’t sell, which is perhaps why they’re calling it “the first drug for agitation in AD.” That’s “first in the USA.” Not everywhere else. And, of course, as soon as it’s approved in the US, the pressure will be on every other government in the world to approve it, too.
What does this add up to? I think we are seeing a major change in the drug companies and their hired hands in psychiatry. Having long ago discarded the idea that mental disorder is mental in origin, they are slowly realising they don’t actually know anything about the brain. Their research pipelines are empty, and the patents on their old, toxic drugs are running out. So they are developing new “diseases” which require hugely expensive new drugs for governments to fund. Which, of course, amounts to new diseases for old drugs.
References
1. Moncrieff, J., Cooper, R.E., Stockmann, T. et al. (2022) The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry Published online July 20th 2022. https://doi.org/10.1038/s41380-022-01661-0
2. McLaren N (2011). Cells, circuits and syndromes. A critique of the NIMH Research Domain Criteria project. Ethical Human Psychology and Psychiatry 13: 229-236