Did Psychiatry Ever Endorse the Chemical Imbalance Theory of Depression?

With the chemical imbalance theory falling out of fashion, researchers examine the claim that psychiatry never truly endorsed it.


In a new article published in the journal Mental Health, Benjamin Ang and his colleagues explore how psychiatry championed the debunked “serotonin theory” of depression, the assertion that lowered serotonin levels cause depression.

As the evidence against the serotonin theory of depression grows each day, many psychiatrists have claimed that the field never truly embraced this damaging and incorrect theory. To test whether psychiatry championed the serotonin theory of depression, the current work examines highly cited reviews of the causes of depression, highly cited papers that discussed depression and serotonin, and several textbooks published between 1990 and 2012. Despite contemporary psychiatrists’ claims to the contrary, all of the textbooks examined and nearly all academic papers supported this theory despite the lack of evidence.

“The findings suggest that the serotonin theory was endorsed by the professional and academic community,” the authors write. “The analysis suggests that, despite protestations to the contrary, the profession bears some responsibility for the propagation of a theory that is not empirically supported and the mass antidepressant prescribing it has inspired. “

Despite the psy-disciplines knowing that the serotonin theory was incorrect as far back as 1970, modern psychiatrists are still pushing this debunked theory, even as others claim the psy-disciplines never truly embraced it. The serotonin theory led to the common misunderstanding that depression was caused by a “chemical imbalance” in the brain, which led to an explosion in the sale of antidepressants to treat this supposed chemical imbalance. This series of events, paired with the lack of evidence for the serotonin theory, has caused some researchers to wonder if the serotonin theory was, in truth, a marketing scheme carried out by the pharmaceutical industry.

Although antidepressants are still commonly prescribed to treat depression, their efficacy is questioned. The little evidence that does exist is at high risk for bias. There is no evidence that antidepressants treat a “chemical imbalance” in the brain. The lack of evidence for antidepressant efficacy, paired with the mounting evidence of their detrimental effects, has caused some researchers to declare, “It’s time to stop recommending antidepressants for depression.”

The theory that chemical imbalance in the brain causes depression began in the 1960s. Researchers initially focused on noradrenaline rather than serotonin as the problematic neurotransmitter. However, serotonin replaced noradrenaline as the key neurotransmitter in the chemical imbalance theory in the late 1980s, just as pharmaceutical companies rolled out selective serotonin reuptake inhibitors.

In the 1990s, the pharmaceutical industry began aggressively branding depression as an imbalance of serotonin in the brain and SSRIs as a “magic bullet” that could correct this problem. The American Psychiatric Association parroted this pharmaceutical industry misinformation in a 2005 patient leaflet declaring, “antidepressants may be prescribed to correct imbalances in the levels of chemicals in the brain.”

The branding of depression as a chemical imbalance and SSRIs as the remedy has paralleled a massive increase in antidepressant prescriptions. According to the authors, belief in the debunked chemical imbalance theory is common among people using antidepressants. This belief also encourages people to request antidepressants and discourages them from trying to stop taking these drugs.

In 2005, Jeffrey Lacasse and Jonathan Leo published a paper detailing the disconnect between pharmaceutical industry advertising and what the evidence actually said about chemical imbalance theory. This paper inspired prominent psychiatrists to defend the debunked theory by explaining that a “chemical imbalance” was a metaphor rather than a literal description of reality. As the evidence against chemical imbalance theory mounted, many within the psy-disciplines began claiming that psychiatry had never truly embraced “chemical imbalance theory” but that it was instead pushed by the pharmaceutical industry directly to the public with little involvement from the psy-disciplines.

The authors investigate the claim that the psychiatric profession did not promote serotonin theory by analyzing influential research articles and textbooks published between 1990 and 2012. The current research examines 30 reviews of the causes of depression, 30 highly cited papers that explored the connection between serotonin and depression, and a sample of influential textbooks.

23 of the 30 reviews discussed the chemical imbalance theory of depression. And 2 of the seven that did not discuss chemical imbalances were explicitly dedicated to environmental factors of depression. Eleven reviews thoroughly and unequivocally supported the serotonin theory. Additionally, nine reviews proposed that while serotonin was not the primary or only cause of depression, it was involved in depression in a similar manner described by pharmaceutical industry misinformation. Only one paper came out unequivocally against the chemical imbalance theory.

Most of the papers the current research examined explicitly support the hypothesis that serotonin is involved in depression. Four papers admitted that the connection between serotonin and depression was inconclusive but suggested that serotonin was likely involved in depression.

While all the textbooks acknowledged that the causal relationship between serotonin and depression was an unproven hypothesis, they all provided some support for that unproven hypothesis. In addition, the textbooks all dedicated a disproportionate amount of space to describing serotonin systems and how they may affect depression. The authors conclude:

“From our research, it is clear that during the period 1990-2010, there was considerable coverage of and support for the serotonin hypothesis of depression in the psychiatric and psychopharmacological literature. Many of the most highly cited reviews of the etiology of depression endorsed the hypothesis, including some that were entirely devoted to describing research on the serotonin system and those that reviewed the etiology of depression more broadly. Research papers on the serotonin system had very large numbers of citations and most strongly supported the serotonin theory, with a smaller number highlighting inconsistencies in the evidence and adopting a more cautious tone. Textbooks, too, though taking a more nuanced line in places, at other points presented unequivocal support for the theory.”



Ang B., Horowitz M. & Moncrieff J., Is the chemical imbalance an ‘urban legend’? An exploration of the status of the serotonin theory of depression in the academic literature, SSM – Mental Health (2022), DOI: https://doi.org/10.1016/j.ssmmh.2022.100098.(Link)


  1. Thank you, Richard, for publishing this analysis. Many nails have already been pounded into the coffin of the chemical imbalance theory, and it looks likes we’re all getting close to ridding ourselves of this harmful and destructive idea.

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  2. what is the title of Szasz’s final book…Psychiatry: the science of lies, or…something like that, anyway. and so…

    yeah. lies. lying liars turned their craft into a -science-, complete with MD/DO degrees and real pills for fake diseases.

    and, now? now and then, out of…I suppose curiosity mixed with a touch of boredom…I check out the mainstream, health information sites to see what these sites have about the various psych drugs. and…

    even now, I see “correct…imbalances…natural brain chemicals…” sort of psych-lies pop up. and…then one has the more honest sites (not that it matters much, but I think WebMD is still bigger with the debunked lies, other sites have taken a more honest, less sugar coated approach…) will have a more correct take on it, for instance emphasizing the “tranquilizing effect” of “antipsychotics” (not -quite- to the point at which these pills are referred to correctly, as neuroleptics or major tranquilizers…but OK…), which is a a result of blocking dopamine and often serotonin, blah blah blah.

    the truly sad, honestly…to me, frightening…lingering result of the lies about “imbalances” and the magical meds that “correct” them? now, the pills are so ubiquitous, the lies so obvious, the options so generally non-existent…

    “ugh, take your medicine.” odd, add, adhd, sad…mix n match from the alphabet soup of lies and lingo…

    take your pills, asap. 🙁

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  3. The big hassle here is that “depression” is misinterpreted as a disease unto itself instead of a syndrome likely to have differing causes, which is why you have individuals carelessly labeled as suffering from a disease called depression, when such isn’t the case. This is also why you have patients with this “disease” losing their marbles when (erroneously) prescribed antidepressants.

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    • While this is a valid point, this research is not about the technical details about various mental conditions, but about the deception used by a professional group to make itself look like it was doing something helpful when it really wasn’t. Though this is certainly not the only profession where this has happened, this profession in the focus of this website and in this context, this context is definitely unethical.

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  4. This is a valuable article, but psychiatry’s errors of omission and commission go much deeper than what appeared in the peer reviewed journals.

    Psychiatrist Daniel Carlat, in “Unhinged,” a so-so expose of psychiatry, debunked the “chemical imbalance theory,” while admitting he promoted it to patients to induce them to take SSRI’s:

    ” … when psychiatrists start using what I call neurobabble, beware because we rarely know what we are talking about. I fall into this habit with patients all the time. When I find myself using phrases like “chemical imbalace” and serotonin deficiency,” it is usually because I’m trying to convince a reluctant patient to take a medication. Using these words makes their illness seem more biological, taking some of the stigma away from having a mental illness. The implicit message I deliver in using such language is “Your illness is biological, it is not your fault and you are not going to be able to cure it by thinking it away.”

    Indeed, how could mental illness not be, ultimately, biological? All thoughts and emotions come from the brain, and so disordered thoughts and emotions must come from a disordered brain. But few laypeople realize how little we actually know about the underpinnings of these disorders.” (“Unhinged,” 2020, at 74-75)

    He’s clearly a smart guy, but his words reveal how compromised most individual psychiatrists truly are. He knows he’s BS-ing patients, but he attributes his doing so to “falling into this habit,” and says he “finds” himself doing that – like he finds himself eating too much popcorn at the movies, or he’s “falling into this habit” as though he’s spending too much time on Twitter.

    No – he’s lying to patients.

    And he’s one of the more self-aware and feisty psychiatrists who dared to speak out about psychiatry’s flimsy “evidence.” But the trick is that he, like a number of other psychiatrists, knows where the line is and doesn’t cross it. Psychiatry tolerates a certain amount of internal criticism, as long as it doesn’t cross that line. Carlat saves himself by saying he does prescribe psych drugs, and by supporting psychiatry’s claim that “mental illness” is “ultimately biological.” So he remains in the club, even though his reasoning is ridiculous: to say the brain is involved in thoughts and emotions does not prove mental suffering is due to “disordered” brains – any more than saying all car accidents involve cars necessarily means that all car accidents are caused by mechanical malfunctions. In fact, somewhere around 95% of all accidents are caused by environmental factors external to the car’s mechanics – black ice, snow, fog, drunken/distracted/speeding drivers – essentially the environmental input in which the car is operating.

    And where were psychiatrists when the evidence against “chemical imbalance” was accumulating? Only a handful bothered to point out that evidence. They were perfectly willing to repeat PhARMA’s ad copy as though it were science. For the most part, even PhARMA’s ads didn’t expressly claim the “chemical imbalance theory” was factual. Mostly, they said, “While the exact cause of depression isn’t fully known, it is thought to involve low serotonin etc. etc.” Cloaking itself in the mystique of science was enough for PhARMA to persuade the public, and psychiatrists were happy to go along for the ride, without going out of their way to tip off the public.”

    So Dr. Pies can disingenously call this theory “urban myth” that psychiatry never fully endorsed. There may have been some level of doubt in some psychiatrists’ minds, but they were happy not to rock the boat, riding the gravy train as far is it would take them, rationalizing the deception and its damage as they went.

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    • What you are saying is true. However there is the reason why they are going down this road. They, as well as the entire medical science in general, are saying “it’s a meat robot so disease is a malfunction or damage in the machine” This then leads psychiatrists and medical scientists in the area to say to themselves “well, if it a mental illness, then there has to be something wrong in the brain. Makes sense doesn’t it?”
      This reasoning has lead them down the path of chemical imbalances theory for mental illness.
      If only they were to put their thinking caps on. Some 80% of people with depression have severe anxiety. Anxiety is not just a form of fear / fight or flight response. If they ask patients they find that for the most part anxiety patients will talk about fear but they will also talk about worry. Fear and worry are not the same thing, not by a long way.
      They see a fight or flight response in patients with anxiety and depression. However they dismiss as delusional anyone saying that they have a bad gut feeling of there being others in their life wanting to do them harm. A fight or flight response cannot arise without the perception of danger.. real danger. So there is an elevation of the metabolism.
      Worry requires the person to be able to think and reason and try to find a solution to some perceived problem. In the fear response the thinking areas of the brain are declined in favor of perception in order to gain the information needed for thinking and finding a solution. So the body moves to resting metabolism to facilitate thinking and bring back the thinking parts of the brain to full capacity again.
      Once the person starts thinking they again become highly aware of the danger so back to fight or flight response and raised metabolism.
      SO, what is happening that can cause depression? What is happening is the heart becomes conflicted. The heart gets signals to go fast (fear response) then signals to go slow (worry needed) and then signal to go fast again and so on. Go fast, go slow, go fast, go slow. The heart becomes conflicted and there is spasm of cardiac muscles. The end result is that the heart is unable to pump blood sufficiently to facilitate all of life’s requirements and certainly can’t respond to excitement that is part of pleasure.
      This is seen in that the heart variability is affected. The heart becoming conflicted as a pump is the reason why the metabolism is low and stays low, i.e., depression.
      And there is more too. They see immune system markers, not in the brain but in the blood. This is not to do with any inflammation of neurons in the brain, but heart muscle spasm and sometimes damage happens so there is an immune response.
      So they haven’t thought the problem out properly. It is not a meat robot but a conscious being having physical experiences through their physicality, the body. This means ideas, negative ideas have a big impact. This is the source of the problem. Where do those ideas come from? This is not being addressed but in fact trashed so that the chemical imbalance theory, which is financially expedient is seen as favorable. They can see patients for 10 to 15 mins long enough to write a new prescription and next patient enters. They can see 30+ patients a day rather than 8! And life is easy.

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      • This is all quite valid as an observation of what has been going on in this field.

        I can only add that modern alternative ideas and therapies have been available since the 1950s, and were disregarded or purposely dismissed without any actual testing.

        Thus, not only is the “meat robot” idea misguided, there are some pushing this idea who have a vested interest in it remaining the dominant idea about human life, regardless of how ineffective it has been in helping people get better.

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        • The “meat robot” idea enables them to justify drugs as treatments. And of course that means profits. But like you say it is not effective treatments.
          I have found that with all disease, not just mental illness, it is a nocebo effect. This means that there are negative ideas that the person reacts to and that reaction is physiological. Those ideas don’t arise of their own accord out of any mythical subconscious mind, but rather they are presented to the person by someone related and inhumane and who has some agenda. This has been brushed aside by discrediting ESP and telepathy. They first used only unrelated subjects and now with related subjects but still with issues that are totally irrelevant like the picture on a card.
          Once the person realizes that the ideas are not their own thinking and thus carry no authority, they can then simply and easily discard the ideas. Thus they don’t react to them. They can then maintain their health.
          I am making a series of videos on the Underlying Conditions of Disease. If you are interested I can post the link here.

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          • Are you inventing your own therapy?

            I notice you have followed CCHR but have an issue with them. Do you consider there is something wrong with the other alternative therapies out there?

            Do you think the only form of triggering is from the presence of a toxic personality? You don’t allow the possibility that triggering can take other forms and that the responses are supplied by the person who gets triggered and not by the toxic personality?

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    • yes! the talking section of the guild is often -worse- than the witchdoctors at pushing “treatment for ‘imbalances, ‘ ” etc. I think…its supposed to be some sort of “no-fault” approach to “treatment…”

      its an “imbalance,” because apparently the person/patient’s brain just broke one day, which the “miracle meds” can correct (hooray!), not a result of personal failings, social problems, economic issues, personal history, abuse and/or mistreatment, or…you know, life hitting an individual, in any number of different ways. no, no…not that, not that -at all- . definitely an “imbalance.” definitely.

      thing is…without going deep into “bitter ex-patient” territory, here…the talking ones are often just as prone to fraud and deliberate destruction as the pill and shock docs, and they also seem to be more threatened by people with resources or access to resources, any sort of education or intellectual ability, on and on. Personal experience: counselors, in particular, seem to be taking over the talking section in droves. I guess its sort of like the equivalent of using highly trained nurses instead of doctors? sufficient credentials, lower costs…something like that, anyway.

      problem? especially in the psych guild, which in the US is (of course…and yes, this is Szasz material, yet again) a pseudoscientific, religious control system operating to maintain the current neoliberal capitalist system…

      the “professionals” who are, themselves, on the very edge of the middle-middle class and profiteering and defrauding the vulnerable…

      have — in my own, limited experience — proven even more dangerous than some of the higher status professionals. Some critiques of the industry I’ve skimmed over point that the mass produced master’s level counselors a) are not given the “correct training” or…something and b) that the training programs, themselves, leave much to be desired. I suppose that if I thought that any of the psych guild could be reformed and possibly made “helpful,” I might (?) buy into that line of thought, but…

      as society continues to modernize and such, people are required to obtain more and more credentials. Seems to be more pronounced in some nations, some economies than in others. Some European nations, for instance, wisely track their students into skilled vocational training (which I would assume involves obtaining credentials, too…) rather than telling people to go to college and get a 4 year degree and live the (dying, largely fictional from the beginning…) American Dream, etc. Point there is…there’s lots of people, in lots of fields, who have mass produced degrees that they obtain without developing much in the way of critical thinking or analytical skills, writing skills, etc., because…

      that’s what is bound to happen when the economy demands more and more credentials, and when society places more value on a masters level counselor than a well trained HVAC technician who probably makes more per year (and actually benefits the common good!). 🙂

      but…yeah…worse troubles with counselors than psychologists or nurse practitioners. psychiatrists…hellish, but that’s to be expected.

      The “imbalance theory” was, at best, a fun lie masquerading as a necessary over-simplification. Dig a little deeper, and…

      lies, lies, lies. fraud, fraud, fraud. The deception is deliberate, the destruction is expected. Welcome to Mental Health, Inc. 🙁

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  5. I seem to remember when the distinction was between endogenous and exogenous depressions. The latter were indeed caused by a chemical imbalance while the former were the result of exterior forces. Have we now dropped these distinctions?

    In 1995, I was part of a sample of Tourette’s patients who, because we were so “predisposed,” developed a severe depressions after taking Risperdal and an antidepressant that were prescribed to reduce the severity of our tics. (15% of patients who were prescribed the drug regimen developed severe depression.)

    What I understood was that there was an endogenous component to our depression insofar as we were “predisposed.” My question is how does this jibe with the conclusions of the above article? To reiterate, the depression I suffered was chemically induced but not all patients under the drug regimen developed depression. Only those so predisposed supposedly got depressed (and this was very depressed, there were suicides among the 15% of patients predisposed). Are some people because of their genetics more likely to develop depression and how does this jibe with the chemical theory of depression if certain people are more likely to develop depression than others?

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    • This was another trope of the psychiatric/psychological community to justify their drug interventions. There was never any means to distinguish “endogenous” from “exogenous depression.” It’s kind of dropped out of use, since it has served its purpose and allowed the drugging paradigm to take full hold. Now most psychiatrists assume that all “depression” is biologically caused, despite still having no evidence to prove or even suggest that is the case. Note at the end it states “The exact cause of depression is still unknown.” Which really means, “We have NO CLUE of the cause of depression, and we’re making this up!”


      “According to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), anyone experiencing endogenous or exogenous depression will likely receive a diagnosis of major depressive disorder (MDD).

      Medical professionals no longer give endogenous depression as an official diagnosis, and the DSM-5 no longer lists endogenous depression as a diagnostic category. Still, some researchers and mental health professionals find that locating the sources of depression — internal or external — could help you with finding treatment that best suits the specific needs.

      The exact cause of depression is still unknown.”

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      • I would add that the cause of depression is still unknown to the medical/psychiatric community!
        There are other groups who have figured it out. Medicine hopes that the general public NEVER finds out about that.

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        • Well, I think the first mistake is thinking “depression” is a thing that is always caused by the same factors. But I agree, there are certainly many understandable causes for depression that are addressable, once psychiatry’s false categorizations are set aside. And there are many, many things that can be done to help, regardless of the underlying reasons.

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          • Though a full treatment for a reaction like this may not be practical in all cases, I don’t want to leave the impression here that its causes remain a total mystery.

            At the risk of being over-technical, I will summarize my understanding of the situation: Depression (or apathy) is one of many possible psychological reactions to events and environments that may be more or less obvious. In other words, the “triggers” can exist above or below our level of awareness.

            One whole set of valid therapies involves medical care, nutrition, and changing the environment to one that causes less of a problem. It also involves training and educative “therapies” that would help a person to cope with the problem.

            But if time and resources permit, the root cause of the problem can be located and handled. This is not necessarily a quick process. The root cause is unique for every single individual. There is no pat answer that will work for everybody. But there are people who know how to do this and get results.

            My main point in being here and commenting is not to point out that psychiatry is an unethical profession, even within its own set of rules, but that it is acting to hide from us much better solutions.

            Because Psychiatry has been so active in hiding better answers, many of us believe there are none, or that they still have to be discovered. I am simply here to point out that this has been happening and that we, as a species, are in a much better position than most of us believe. It is just a matter of ignoring the unethical “experts” and finding and using the more workable answers that they have been hiding from us.

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          • I particularly agree with your point that everyone’s “cause” is unique to their own life situation, both physiologically and psychologically/spiritually. Trying to come up with one answer for everyone denies this obvious fact. “Depression” is a false category of “disorder.” It is an effect, not a cause. If we want to handle the situation, we have to find the cause, and calling “depression” the problem implies that all “depressions” are caused by the exact same circumstances, which is a silly thing to think.

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  6. Thanks Steve for the feedback and link. Depression is a terrible thing. My depression in 1995 was induced. It was chemical. i will always remember the feeling. I had terrible akathisia. At the same time, there was a part of me that was able to observe what I was feeling from a distance. The mind body separation was a very real thing for me. I was not my physical sensations. Nor was I my emotions. These were tortured. All i felt was shame and regret. Yet another part of me knew these were a side effect.

    It was expected that the depression would pass and my body became accustomed to the drugs — neuroleptics and an anti-depressant (which ironically triggered a depression). It never did. I had to finally change medications. Other patients didn’t have that separation between what they were feeling and what they were thinking and succumbed to the effects of the depression.

    The doctor,Yves Dion, at least had the professional integrity to write an article warning of the possible side effects of the drug therapy that he had prescribed, this after he had refused to believe patients’ when they tried to report to him what they were feeling.

    “Depression and dysphoria in adults and adolescents with Tourette’s disorder treated with Risperidone,” Journal of Clinical Psychiatry; 2002, vol.63

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    • But pretending that we “know” the cause and providing “treatment” on those assumptions clearly leads to destruction. You can provide aspirin or morphine for a broken leg, but you’re not treating “leg pain disorder.” On that basis, getting drunk can be called a “treatment” for “anxiety disorders.”

      And of course, in many, many cases, we DO know the actual cause of a particular case of “depression,” and it is usually NOT due to a physiological event, though sometimes it IS and we know it and we should “treat” the actual problem rather than the “symptoms” (low thyroid would be one example). We certainly know enough to know that “depression” is itself a “symptom” rather than a “disorder” that “causes symptoms.” It would be best for the clients involved if we dropped the whole notion of “depression” as a disorder and started viewing it a symptomatic of something else.

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  7. It is interesting to note that we are only now learning that the latest pesticides ( cf. imidacloprid) are toxic not just for bees but for mammals too. Yet ALL agriculture is now based on this single kind of pesticide and we continue to use it indoors because there is no cost-effective alternative. The same FDA that approves drugs approved these pesticides. But what is the real toxicity of the pharmaceuticals we now also consume in the tons? Even if depression was indeed treatable with drugs, do we have the drugs to treat it safely and effectively? Is it not healthy to be a bit wary about these very powerful drugs that can induce such horrific side effects as akathisia and severe depression (and I speak from experience here)?

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    • Posting as moderator: After a certain number of layers of comments, the “reply” button disappears, so Mr. Cox has no control over this. What you have to do to comment is go back up the thread to the first one that still has a “reply” button and hit it. Your comment will appear next in line.

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  8. Reading both the article and the comments again has impressed on me even more the problematic character of the medical model in psychiatry. Psychiatry, such as it is, is premised on certain assumptions. Yes it is materialist but at the same time it is the least empirical of the sciences. It gambles that the benefits will outweigh the costs. When these do not, it is the patient who pays the costs. Akathisia is the apotheosis of this philosophy. To suffer its depredations is to be acutely aware of the implications of the “medical model” for the object of its interest. And the onus is too often on the patient to prove the cost (in the case of akathisia it is often visible indeed palpable though not always).

    The fact that doctors speak in terms of costs and benefits is telling. It is only over time that these become evident. SSRIs, of course, are still routinely prescribed. When insurance companies refuse to pay for SSRIs because they are deemed inefficient, doctors will stop prescribing them so Yes the medical model has important economic aspects.

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