Article The drug-based approach to mental illness has failed. What are alternatives?

[Syne]

Like MR and Yaz, SS is eager to conflate "biochemical" and neurophysiology.

Brain/nervous system structure, activity, and function can obviously be mediated by genetics, trauma, damage, or disease directly, without any need to postulate "chemical imbalances."

And, yes, there are really two myths to debunk. The first holds that mental illnesses (psychiatric disorders) in general are caused by “a chemical imbalance” in the brain-the so-called “chemical imbalance theory.” The second myth holds that “Psychiatry” as a profession endorsed the first myth, deliberately and knowingly lying to countless, unsuspecting patients.
- https://www.psychiatrictimes.com/view/de...yths-again


Although first proposed in the 1960s, the serotonin theory of depression started to be widely promoted by the pharmaceutical industry in the 1990s in association with its efforts to market a new range of antidepressants, known as selective serotonin-reuptake inhibitors or SSRIs. The idea was also endorsed by official institutions such as the American Psychiatric Association, which still tells the public that “differences in certain chemicals in the brain may contribute to symptoms of depression”
...
For a long time, certain academics, including some leading psychiatrists, have suggested that there is no satisfactory evidence to support the idea that depression is a result of abnormally low or inactive serotonin. Others continue to endorse the theory. Until now, however, there has been no comprehensive review of the research on serotonin and depression that could enable firm conclusions either way.
...
In fact, drug trials show that antidepressants are barely distinguishable from a placebo (dummy pill) when it comes to treating depression. Also, antidepressants appear to have a generalised emotion-numbing effect which may influence people’s moods, although we do not know how this effect is produced or much about it.
- https://www.ucl.ac.uk/news/2022/jul/anal...-new-study


The theory that depression is caused by a serotonin abnormality or other chemical imbalance has become widely accepted by the public and is one prominent justification for the use of antidepressants. However, it has been increasingly questioned and there is little evidence it has empirical support. In response, leading psychiatrists suggested it was an ‘urban legend’ that was never taken seriously by the psychiatric profession.
- https://www.sciencedirect.com/science/ar...032200038X

[Magical Realist]

You're conflating the "chemical imbalance" theory of mental illness with the evidence-based understanding of mental illness as being biochemical in nature. As your own article stated:

"(I hasten to add that debunking the chemical imbalance theory is not to deny that biological factors play an important role in serious mental illness, including but not limited to major depression, bipolar disorder, and schizophrenia)."

Also your article pretty much debunks your claims that the chemical imbalance theory of mental illness was a global deception fabricated by all psychiatrists just to get more money. The theory was never sufficiently evidenced to become accepted as fully explaining mental illness. It was always proposed tentatively whenever I encountered it, as being the best explanation we have so far. Still, the biochemical basis of mental illness is well-established and proven by the effectiveness of various medications over the years.

https://socialsci.libretexts.org/Bookshe...troduction

[Syne]

You're conflating the "chemical imbalance" theory of mental illness with the evidence-based understanding of mental illness as being biochemical in nature. As your own article stated:

"(I hasten to add that debunking the chemical imbalance theory is not to deny that biological factors play an important role in serious mental illness, including but not limited to major depression, bipolar disorder, and schizophrenia)."

Again, you insist on conflating "biochemical" with biological. They are not equivalent. Biochemical does specifically refer to chemicals in the brain (e.g. chemical imbalance theory), while biological, neurophysiological, etc. can refer to structure, activity, and function... without necessarily including chemical imbalance theory.

Biology is the study of living organisms, whereas, biochemistry is the branch of science dealing with the study of chemistry of life. Biochemistry studies about the nucleic acids, proteins, carbohydrates and lipids. Biology studies the anatomy and physiology of living organisms.
- https://byjus.com/biology/difference-bet...chemistry/

Starting to see the distinction, or still just as clueless?

Also your article pretty much debunks your claims that the chemical imbalance theory of mental illness was a global deception fabricated by all psychiatrists just to get more money. The theory was never sufficiently evidenced to become accepted as fully explaining mental illness. It was always proposed tentatively whenever I encountered it, as being the best explanation we have so far. Still, the biochemical basis of mental illness is well-established and proven by the effectiveness of various medications over the years.

I never said psychiatrists perpetrated a global deception. And I DARE to show where you IMAGINE I did.
Chemical imbalance theory, as I've already cited, was primarily an ad campaign by pharmaceutical companies, but was endorsed by the American Psychiatric Association as well. You want try refuting those facts with evidence? Go ahead. I'm all ears.

[Magical Realist]

Again, you insist on conflating "biochemical" with biological. They are not equivalent. Biochemical does specifically refer to chemicals in the brain (e.g. chemical imbalance theory), while biological, neurophysiological, etc. can refer to structure, activity, and function... without necessarily including chemical imbalance theory.

Whenever someone refers to the biological causes of mental illness, they are referring to the influence of genetics, biochemical processes, and the structures of the brain itself on mental illness. Abnormal neurotransmission is a proven biological factor in contributing to mental illness. Scores of studies have proven this as well as the success of many psych meds.

"Abnormal levels of dopamine activity correspond with several disorders (reduced in ADHD and OCD, and increased in schizophrenia). The dysfunction in serotonin and other monoamine neurotransmitters (norepinephrine and dopamine) correspond with certain mental disorders and their associated neural networks. Some include major depression, obsessive-compulsive disorder, phobias, post-traumatic stress disorder, and generalized anxiety disorder. Studies of depleted levels of monoamine neurotransmitters show an association with depression and other psychiatric disorders, but "... it should be questioned whether 5-HT [serotonin] represents just one of the final and not the main, factors in the neurological chain of events underlying psychopathological symptoms...."---- https://en.wikipedia.org/wiki/Causes_of_..._disorders

A list from Merck's Manual of disorders caused by neurotransmission defects:

https://www.merckmanuals.com/professiona...ansmission

but was endorsed by the American Psychiatric Association as well.

LOL Again your own quoted article says otherwise. Don't quote things that refute your own claims.

"In response, leading psychiatrists suggested it was an ‘urban legend’ that was never taken seriously by the psychiatric profession."

[Syne]

Again, you insist on conflating "biochemical" with biological. They are not equivalent. Biochemical does specifically refer to chemicals in the brain (e.g. chemical imbalance theory), while biological, neurophysiological, etc. can refer to structure, activity, and function... without necessarily including chemical imbalance theory.

Whenever someone refers to the biological causes of mental illness, they are referring to the influence of genetics, biochemical processes, and the structures of the brain itself on mental illness. Abnormal neurotransmission is a proven biological factor in contributing to mental illness. Scores of studies have proven this as well as the success of many psych meds.

I JUST gave you the distinction between biology and biochemistry, and you still refuse to comprehend that simple difference.

A list from Merck's Manual of disorders caused by neurotransmission defects:

https://www.merckmanuals.com/professiona...ansmission

Merck? You mean a pharmaceutical company that's used the chemical imbalance theory for advertisement?

but was endorsed by the American Psychiatric Association as well.

LOL Again your own quoted article says otherwise. Don't quote things that refute your own claims.

"In response, leading psychiatrists suggested it was an ‘urban legend’ that was never taken seriously by the psychiatric profession."

For Christ's sake, learn to read for once.
Apparently you don't even understand the simple difference between "leading psychiatrists" and an organization that simply represents psychiatrists in general.
It's not hard to understand. It's like labor unions. The union may endorse and contribute to Democrat politicians, but that doesn't mean that all union members (or even most, where union dues are mandatory) agree with that.

Use your brain for something other than absorbing psych meds and echoing voices.

[Magical Realist]

LOL You don't know what the Merck Manual is?

"The Merck Manual of Diagnosis and Therapy, referred to as The Merck Manual,[1] is the world's best-selling medical textbook,[2] and the oldest continuously published English language medical textbook.[3] First published in 1899, the current print edition of the book, the 20th Edition, was published in 2018."

Are you questioning the information contained in this highly reputable publication? Do you think it made up the data about neurotransmitter defect disorders just to sell more drugs? Do you even know what a neurotransmitter is?

[Syne]

LOL You don't know what the Merck Manual is?

"The Merck Manual of Diagnosis and Therapy, referred to as The Merck Manual,[1] is the world's best-selling medical textbook,[2] and the oldest continuously published English language medical textbook.[3] First published in 1899, the current print edition of the book, the 20th Edition, was published in 2018."

Are you questioning the information contained in this highly reputable publication? Do you think it made up the data about neurotransmitter defect disorders just to sell more drugs? Do you even know what a neurotransmitter is?

The Merck Manuals are medical references published by the American pharmaceutical company Merck & Co.
- https://en.wikipedia.org/wiki/The_Merck_Manuals

But I guess you don't see that as any kind of conflict of interest.

At least the DSMV isn't directly published by a pharmaceutical company.

---

By 1960, the major classes of psychiatric drugs—among them, mood stabilizers, antipsychotics, antidepressants, and anti-anxiety drugs, known as anxiolytics—had been discovered and were on their way to becoming a seventy-billion-dollar market. Having been discovered by accident, however, they lacked one important element: a theory that accounted for why they worked (or, in many cases, did not).

That didn’t stop drug makers and doctors from claiming that they knew. Drawing on another mostly serendipitous discovery of the fifties—that the brain did not conduct its business by sending sparks from neuron to neuron, as scientists previously thought, but rather by sending chemical messengers across synapses—they fashioned an explanation: mental illness was the result of imbalances among these neurotransmitters, which the drugs treated in the same way that insulin treats diabetes.

The appeal of this account is obvious: it combines ancient notions of illness (specifically, the idea that sickness resulted from imbalanced humors) with the modern understanding of the molecular culprits that make us suffer—germs. It held out the hope that mental illness could be treated in the same way as pneumonia or hypertension: with a single pill. Drug companies wasted no time in promulgating it. Merck, the manufacturer of Elavil, commissioned the psychiatrist Frank Ayd to write a book called Recognizing the Depressed Patient, in which he extolled the “chemical revolution in psychiatry” and urged doctors to reassure patients they weren’t losing their minds, but rather suffering a “common illness” with a “physical basis” and a pharmacological cure. Merck sent Ayd’s book to fifty thousand doctors around the country. In 1965, Joseph Schildkraut, a psychiatrist at the National Institute of Mental Health, reverse-engineered antidepressants and offered an actual theory: at least when it came to depression, the imbalances were to be found in the neurotransmitters he thought were affected by the drugs, dopamine and norepinephrine. Seven years after antidepressants were invented, and five years after Ayd asserted that depression was a chemical problem, psychiatrists finally had a precise, scientific explanation for why they worked. The paper quickly became one of the most cited articles in the medical literature.

But Schildkraut was wrong. Within a few years, as technology expanded our ability to peer into the brain, it became clear that antidepressants act mostly by increasing the availability of the neurotransmitter serotonin—rather than dopamine and norepinephrine, as previously thought. A new generation of antidepressants—the selective serotonin reuptake inhibitors (S.S.R.I.s), including Prozac, Zoloft, and Paxil—was developed to target it. The ability to claim that the drugs targeted a specific chemical imbalance was a marketing boon as well, assuring consumers that the drugs had a scientific basis. By the mid-nineties, antidepressants were the best-selling class of prescription medications in the country. Psychiatry appeared to have found magic bullets of its own.

The serotonin-imbalance theory, however, has turned out to be just as inaccurate as Schildkraut’s. While S.S.R.I.s surely alter serotonin metabolism, those changes do not explain why the drugs work, nor do they explain why they have proven to be no more effective than placebos in clinical trials. Within a decade of Prozac’s approval by the F.D.A. in 1987, scientists had concluded that serotonin was only a finger pointing at one’s mood—that the causes of depression and the effects of the drugs were far more complex than the chemical-imbalance theory implied. The ensuing research has mostly yielded more evidence that the brain, which has more neurons than the Milky Way has stars and is perhaps one of the most complex objects in the universe, is an elusive target for drugs.

Despite their continued failure to understand how psychiatric drugs work, doctors continue to tell patients that their troubles are the result of chemical imbalances in their brains. As Frank Ayd pointed out, this explanation helps reassure patients even as it encourages them to take their medicine, and it fits in perfectly with our expectation that doctors will seek out and destroy the chemical villains responsible for all of our suffering, both physical and mental. The theory may not work as science, but it is a devastatingly effective myth.
- https://www.newyorker.com/tech/annals-of...rug-crisis

[Magical Realist]

But I guess you don't see that as any kind of conflict of interest.

LOL Then every use of any medication for any condition whatsoever listed in the Merck Manual is also untrue? That's quite a litany of medication-treated ailments. Diabetes? Vaccines for viruses? Cancer treatments? Antibiotics? Pain medications? Merck the big evil Pharma making up studies and diseases just to make itself richer by selling drugs? You'd think medical science would've caught such a massive deception going on by now. But nope? They are all dupes of Merck?

Within a decade of Prozac’s approval by the F.D.A. in 1987, scientists had concluded that serotonin was only a finger pointing at one’s mood—that the causes of depression and the effects of the drugs were far more complex than the chemical-imbalance theory implied.

Yes...antidepressants target the mood. Depression is a mood disorder. They don't cure it. But they alleviate the symptoms. And they do it biochemically. Much as diabetes medications treat the symptoms of that disease but don't cure it. Millions benefit from the effects of antidepressants keeping them from getting depressed and committing suicide. And that's a very good thing. And until we come up with an actual cure for depression, it remains the first line of treatment for it. I should know. I have benefited from them for a long time.

"Antidepressants work – some more effectively than others – in treating depression, according to authors of a groundbreaking study which doctors hope will finally put to rest doubts about the controversial medicine.

Millions more people around the world should be prescribed pills or offered talking therapies, which work equally well for moderate to severe depression, say the doctors, noting that just one in six people receive proper treatment in the rich world – and one in 27 in the developing world.

If cancer or heart patients suffered this level of under-treatment, there would be a public outcry, they say.

“Depression is the single largest contributor to global disability that we have – a massive challenge for humankind,” said John Geddes, professor of epidemiological psychiatry at Oxford University. It affects around 350 million people worldwide and instances rose almost 20% from 2005-2015.

“Antidepressants are an effective tool for depression. Untreated depression is a huge problem because of the burden to society,” said Andrea Cipriani of the NIHR Oxford Health Biomedical Research Centre, who led the study.

In the UK, Geddes said “it is likely that at least one million more people per year should have access to effective treatment for depression, either drugs or psychotherapy. The choice will need to be made by doctor and patient.”

The debate over antidepressants has unfortunately often been ideological, said Cipriani. Some doctors and patients have doubts over whether they work at all and point to the big placebo effect – in trials, those given dummy pills also improve to some degree. Some people suspect drug companies of fiddling trial results. Some patients simply do not want to take pills for a mental health condition.


The study published in the Lancet took six years, Cipriani said, and included all the published and unpublished data that the scientists could find. It was carried out by a team of international experts. They looked at results after eight weeks of more than 500 trials involving either a drug versus placebo or comparing two different medicines.

The most famous antidepressant of them all, Prozac – now out of patent and known by its generic name, fluoxetine – was one of the least effective but best tolerated, measured by a low drop-out rate in the trials or fewer side-effects reported. The most effective of the drugs was amitriptyline, which was the sixth best tolerated.

In a commentary in the journal, Sagar Parikh from the University of Michigan in the USA and Sidney Kennedy from the University of Toronto in Canada pointed out that three drugs scored best for efficacy and tolerability: agomelatine, escitalopram, and vortioxetine. Three others scored particularly poorly: fluvoxamine, reboxetine, and trazodone. The first three “might be considered first choice” by doctors, they write, although the two most effective drugs – amitriptyline and venlafaxine – might still be first choice for severe depression.

But Cipriani said any of the drugs might still have their uses. The trial data cannot show which drug would be likely to work best for any one individual.

Antidepressants and psychological therapies – of which the most frequently used is CBT (cognitive behaviour therapy) – have similar success rates. Around 60% of people respond by about two months to the drugs with about a 50% reduction in their symptoms - an improvement in mood, better sleep and so on. But, he said, “about 80% of people stop antidepressants within a month”.

https://www.theguardian.com/science/2018...%20so%20on.

[Syne]

But I guess you don't see that as any kind of conflict of interest.

LOL Then every use of any medication for any condition whatsoever listed in the Merck Manual is also untrue? That's quite a litany of medication-treated ailments. Diabetes? Vaccines for viruses? Cancer treatments? Antibiotics? Pain medications? Merck the big evil Pharma making up studies and diseases just to make itself richer by selling drugs? You'd think medical science would've caught such a massive deception going on by now. But nope? They are all dupes of Merck?

False dilemma ad absurdum. We're talking about psych meds, and specifically the chemical imbalance theory.
You trying to bring up cancer treatments, antibiotics, etc. just reeks of desperation... or imbecility.

Again, you're the only one trying to posit conspiracies. But I guess it comes so naturally for you.

Within a decade of Prozac’s approval by the F.D.A. in 1987, scientists had concluded that serotonin was only a finger pointing at one’s mood—that the causes of depression and the effects of the drugs were far more complex than the chemical-imbalance theory implied.

Yes...antidepressants target the mood. Depression is a mood disorder. They don't cure it. But they alleviate the symptoms. And they do it biochemically. Much as diabetes medications treat the symptoms of that disease but don't cure it. Millions benefit from the effects of antidepressants keeping them from getting depressed and committing suicide. And that's a very good thing. And until we come up with an actual cure for depression, it remains the first line of treatment for it. I should know. I have benefited from them for a long time.

Yet, the previous sentence said:

"...they have proven to be no more effective than placebos in clinical trials."

That literally means they are no more efficacious then placebo, and as you cite below, Prozac "was one of the least effective but best tolerated."
So inducing a placebo effect with the least side effects. Sounds familiar:

...and to the placebo effect, so it's only a matter of finding an ineffective drug with the least pronounced side effects.

"Millions more people around the world should be prescribed pills or offered talking therapies, which work equally well for moderate to severe depression, say the doctors.
...
Antidepressants and psychological therapies – of which the most frequently used is CBT (cognitive behaviour therapy) – have similar success rates."

Do you even read your own citations? That literally says "talking therapies... work equally well for moderate to severe depression."

"Some doctors and patients have doubts over whether they work at all and point to the big placebo effect – in trials, those given dummy pills also improve to some degree."

Same as I've repeatedly said about the placebo effect.

It doesn't seem you even read your own citations, since they don't support your argument.

[Magical Realist]

"Antidepressants work – some more effectively than others – in treating depression, according to authors of a groundbreaking study which doctors hope will finally put to rest doubts about the controversial medicine.

Millions more people around the world should be prescribed pills or offered talking therapies, which work equally well for moderate to severe depression, say the doctors, noting that just one in six people receive proper treatment in the rich world – and one in 27 in the developing world."----- https://www.theguardian.com/science/2018...%20so%20on

"Clinical trials provide compelling evidence for antidepressant effectiveness, with thousands of positive trials over the past five decades [Hollon et al. 2002]. Randomized controlled trials (RCTs) are the gold-standard methodology for assessing efficacy, in which patients are assigned in a double-blind fashion to a placebo (inert ‘sugar pill’) or active-drug group.

Meta-analyses of RCTs typically report antidepressants as 20–30% more effective than placebo, with higher response rates (50% reduction in Hamilton Depression Rating Scale [HDRS] scores) and improved remission rates (HDRS score of less than 8) [Davis et al. 1993; Walsh et al. 2002; Arroll et al. 2005]. Meta-analyses indicate antidepressant effectiveness varies as a function of symptom severity, with greatest efficacy in severe depression. For example, Khan and colleagues found greater symptom change as baseline HDRS scores increased in patients taking antidepressants, whereas no significant relationship was found with placebo [Khan et al. 2002]. Similarly, Fournier and colleagues found the effectiveness of imipramine and paroxetine was markedly superior to placebo in patients with highest levels of depression severity [Fournier et al. 2010].

Although there is significant variation in the pharmacodynamics of drug receptor and transporter-binding profiles, at a population level there is little evidence to differentiate the various antidepressants’ efficacy, and prescribing is generally based upon tolerability. However, it is well recognized that there is significant individual variation in response to different medications, although the so-called pharmacogenetics of such variation is only poorly understood at this time. Recent meta-analyses, which have attracted attention and criticism in equal measure [Cipriani et al. 2009a, 2009b, 2009c], suggest modest superiority of mirtazapine, escitalopram, venlafaxine and sertraline over duloxetine, fluoxetine, paroxetine and reboxetine, and when acceptability and cost are added sertraline emerged with the best profile. The modesty of the superiority and the short-term follow up of many trials analysed must temper these intra-class difference results.

Nevertheless the many positive RCTs and millions of patients benefitting from antidepressants is compelling evidence that antidepressants are effective in depression management. This is complemented by neurobiological evidence implicating the importance of the medication-targeted monoamine system in depression, e.g. decreased 5HT levels in cerebrospinal fluid and reduced 5HT1A receptor binding potential using positron emission tomography (PET) in depressed patients [Bhagwagar et al. 2004]. Further, decreasing 5HT levels via tryptophan depletion (a 5HT precursor) causes relapse of depressive symptoms in previously depressed individuals [Smith et al. 1997]....

Antidepressants offer substantial benefits in the short and long term to millions of people suffering from depression. To cast them as ineffective is inaccurate and, whilst Kirsch and colleagues opened our eyes to potential bias and inflation in the literature, the potential for such studies to be sensationalized by the media is merely destructive to both drug companies and patients."--- https://pmc.ncbi.nlm.nih.gov/articles/PMC3736946/