Three Books about the Chemical Imbalance Theory of Mental Illness

I highly recommend the two-part article by Marcia Angell in recent issues of the New York Review of Books.   In June, she wrote a piece entitled ‘The Epidemic of Mental Illness:  Why?’; then in the July issue, she followed up with another piece entitled ‘The Illusions of Psychiatry.’ In these two articles, she discusses several important books that address the “epidemic” of mental illness in this country, including Robert Whitaker’s book
Anatomy of an Epidemic which I reviewed in three separate posts:  one about the theory that mental illness is caused by a chemical imbalance in the brain, another concerning the actual effects of psychiatric medications and the third addressing the entirely false belief that treating psychological disorders with such drugs is like taking insulin for diabetes.  Marcia Angell is a Senior Lecturer in Social Medicine at Harvard Medical School and a former Editor in Chief of the New England Journal of Medicine; these lengthy articles are thorough and scholarly.

The other two books under review are The Emperor’s New Drugs:  Exploding the Antidepressant Myth by Irving Kirsch and Unhinged:  The Trouble with Psychiatry — a Doctor’s Revelations About a Profession in Crisis by Daniel Carlat.  I haven’t yet read these two latter books, but here is Marcia Angell’s description of them:

“The authors emphasize different aspects of the epidemic of mental illness. Kirsch is concerned with whether antidepressants work. Whitaker, who has written an angrier book, takes on the entire spectrum of mental illness and asks whether psychoactive drugs create worse problems than they solve. Carlat, who writes more in sorrow than in anger, looks mainly at how his profession has allied itself with, and is manipulated by, the pharmaceutical industry. But despite their differences, all three are in remarkable agreement on some important matters, and they have documented their views well.”

Their first point of agreement is that the companies who manufacture psychoactive drugs have had a disturbing influence upon how we define the mental illnesses their drugs supposedly treat.  Angell covers this subject in detail.  For anyone unfamiliar with how drug companies test drugs, apply for and then receieve FDA approval, her discussion should be an eye-opener.  Other authors, including Joseph Glenmullen in Prozac Backlash, have also covered this territory.  I recommend you to inform yourselves on this important subject as it concerns not only psychoactive medications but every other drug currently being prescribed.

Second, none of the authors subscribes to the theory that mental illness is caused by a chemical imbalance in the brain.  As I discussed in my earlier posts, Whitaker has addressed and debunked this theory in the Anatomy of an Epidemic.  Angell briefly reviews the science of brain chemistry, which I also discussed, and goes on to explain how this theory evolved:  because certain drugs were found to affect neurotransmitter levels in the synapse, and to have an affect on psychosis, anxiety or depression, scientists developed a theory that those disorders were caused by abnormalities in neurotransmitter levels.

As Angell puts it, “instead of developing a drug to treat an abnormality, an abnormality was postulated to fit a drug.” She points out the large leap in logic involved in such a theory.  As author Carlat explains, “‘By this same logic one could argue that the cause of all pain conditions is a deficiency of opiates, since narcotic pain medications activate opiate receptors in the brain.’” All three of these authors document the complete failure of scientists to discover any empirical evidence for the chemical imbalance theory.

Nor do psychoactive drugs have the dramatic effects that have been advertised.  Angell provides a great deal of information about the way drug companies selectively publish studies that demonstrate a positive outcome.  Then she summarizes Kirsch’s review of ALL the double-blind placebo studies on anti-depressants, including those obtained from the FDA under the Freedom of Information Act (and of course, never published).  What he found, for readers of Whitaker, will come as no surprise:

“the relatively small difference between drugs and placebos might not be a real drug effect at all. Instead, it might be an enhanced placebo effect, produced by the fact that some patients have broken [the] blind and have come to realize whether they were given drug or placebo. If this is the case, then there is no real antidepressant drug effect at all. Rather than comparing placebo to drug, we have been comparing ‘regular’ placebos to ‘extra-strength’ placebos.”

Thereafter follows a discussion of Whitaker’s book; as I’ve already covered Anatomy in earlier posts, I’ll omit her synposis of its main points.  She concludes the first part of her review with the following question:   “Why is the current against which Kirsch and Whitaker and … Carlat are swimming so powerful?”  She addresses this subject in the July issue of the New York Review, with particular reference to the extraordinary influence
within our society of the American Psychiatric Association’s Diagnostic and Statistical Manual IV (DSM-IV).

In this second part of her review, Angell covers the story told in detail by Whitaker, about how the APA “launched an all-out media and public relations campaign” to re-invent and “remedicalize” itself during the 1970s when the profession’s reputation was at its nadir:

“Since psychiatrists must qualify as MDs, they have the legal authority to write prescriptions. By fully embracing the biological model of mental illness and the use of psychoactive drugs to treat it, psychiatry was able to relegate other mental health care providers to ancillary positions and also to identify itself as a scientific discipline along with the rest of the medical profession. Most important, by emphasizing drug treatment, psychiatry became the darling of the pharmaceutical industry, which soon made its gratitude tangible.”  She ties this PR effort to the release of the DSM-III in 1980, which shifted the focus of earlier versions from Freudian explanations of mental illness to a biological/medical model.

According to Carol Bernstein, last year’s President of the APA, “It became necessary in the 1970s to facilitate diagnostic agreement among clinicians, scientists, and regulatory authorities given the need to match patients with newly emerging pharmacologic treatments.”  In other words, the revision to the DSM-III was driven, not by
scientific discoveries or advances in our biological understanding of mental illness, but by the need to legitimize the APA’s efforts to medicalize mental health treatments in conjunction with the drug companies and to secure its hegemony over the profession.  The DSM-III went on to become the bible of psychiatry.  And like the “real Bible, it depended a lot on something akin to revelation. There are no citations of scientific studies to support its decisions.” Subsequent revisions did little to remedy this defect.

Angell then takes up the symbiotic relationship between the APA and the pharmaceutical industry, ground also covered by Glenmullen in Prozac Backlash.  While drug companies support other medical specialties and professional societies, the psychiatric profession is its special darling because, as Carlat notes, “Our diagnoses are subjective and expandable, and we have few rational reasons for choosing one treatment over another.”  That is to say, given the lack of “rational reasons” to choose one medication over any other, Key Opinion Leaders in the profession recommend drugs from the pharmaceutical company that supports their research and lavishes benefits upon them.

The second part of her review concludes with a long description of revisions to the upcoming DSM-V, the enlargement of diagnostic categories and the creation of entirely new ones, along with conflicts of interest (i.e., ties to the drug companies) within the community of professionals responsible for this revision.  It makes for disturbing reading.

Regardless of whether you intend to read these books, I recommend Dr. Angell’s thorough and rigorous review.  If you’re not already a psychopharmacology skeptic, this look at three important critiques of the psychiatric profession ought to make you one.

By Joseph Burgo

Joe is the author and the owner of, one of the leading online mental health resources on the internet. Be sure to connect with him on Google+ and Linkedin.


  1. Hi Joseph. I agree with the critiques of the bio-medical model. And anti-depressants in my opinion (and hers) have saved my partner’s life. Denying the chemical can be reductionist too.

    1. As I’ve said in other posts and comments, I do believe anti-depressants have their place in SHORT-term treatment and that they have saved many people’s lives. They are useful in stabilizing extremely depressed and suicidal people. But the side-effects and complications of long-term use far outweigh the benefits. I believe the statistics for post-6 week usage speak for themselves. No one can argue with you when you say anti-depressants saved your partners lives. No one can argue with anecdotal evidence. If you look at the large-scale studiess involving many people on these drugs, there is no statistical evidence of any benefit after those initial 6 weeks. Then there are the side-effects.

  2. Hi Joseph you’ll forgive me I’m sure if I rate my partner’s life above statistical levels of significance.

    This is the problem of applying research to clinical reality – or ‘the anecdotal’. My partner’s life trumps the research (even if it was 100% which the studies never are). A big discussion I know.

    My attitude to the research is that it can be useful as a guide and maybe set the boundaries of the ballpark.

    1. I certainly don’t want to talk anyone out of using meds, especially if he or she feels they are life-saving. The more serious issue, as I’m sure you’d agree, is the indiscriminate prescribing of these drugs by GPs with little follow-up, and their factory-like distribution by psychiatrists who see a patient for 15 minutes and write script. Given the lack of evidence for their usefulness, and the proven long-term side effects, this is a major problem.

  3. Thank you, Joe, for bringing up such important information…what your blog also made me think of is how many people I know who are taking medication because of untenable situations in their lives, say for example with their partners, instead of changing their circumstances. Sometimes to the outside eye, it’s very clear what is making them depressed. There are times we need to heed our depression as a signal/symptom that there is indeed something in our lives that needs to change.

    Our society’s intolerance for any “mood” that is not a good or positive one certainly doesn’t help matters, and the pharmaceuticals both create and feed into that attitude.

    I like Thomas Moore’s book “The Care of the Soul,” in which he calls depression “the winter of the soul,” part of the natural ebb and flow of being human.

    Marla Estes

    1. Excellent points, Marla. I hadn’t thought before about the way our society’s intolerance for negative emotions coincides with the financial interests of the pharmaceutical industry in “curing” them. Thanks for bringing that up.

  4. For sure psych med , like all meds are misused and misunderstood by both docs and patients. I don’t think anyone knows the actual mechanism that SSRI’s use to relieve depression , and there are side effects to consider. Even when clients are told they’re receiving placebos they often get better anyway. Getting the body’s inherent chemical regulation ” balanced” Somehow is the only important personal (as opposed to scientific) issue. I know in my [anecdotal] case and one of my dearest friends, as well as countless clients over the decades, various psych drugs prescribed by artistic expert specialists have allowed relatively “normal” lives when nothing else did–even good psychotherapy. In many cases, the meds allowed folks to access and use psychological approaches which they couldn’t before. I suggest using whatever works, and that’s often a combo of talk therapy and meds , when neither alone was sufficient.

  5. I was diagnosed as manic-depressive in 1976 at age 21. I was prescribed Lithium, and no other drugs. Suffered another manic episode in 1977, and again prescribed Lithium. I was fortunate to have good Lithium blood test results for 32 years and no episodes. In 2009, I suffered severe depressive episode. It did not require hospitalization, but I was prescribed numerous anti-anxiety drugs: Generic Zoloft, Clonazepam, and tested others. My question is; was the lithium enough for the “bipolar”? I’ve been given the “diabetics need insulin.” quote twice by doctors. Thinking I have a chemical imbalance makes my condition easier to accept. My manic breakdowns were extreme. Is this merely the difference between 1976 and 2011?

    1. I’m not sure what you mean, about the difference between 1976 and 2011. One of the points Whitaker makes is that the same arguments have been made all along, for lithium as well as the SSRIs. I understand that thinking you have a chemical imbalance makes your condition easier to accept. I believe many people feel that way, and it’s why that explanation is so popular, despite the lack of evidence for it. Have you had any “talk therapy”?

      1. I mentioned the years, because of the changing nature of psychology. Lithium was discovered in the 1950’s I believe. After my hospitalizations, I had therapy for approximately two years, but it was talk therapy. My therapist just sat and listened. I’m having issues about finding a good therapist. I don’t fear therapy, but there seems to be an infinite quality about it. Thank you for the response.

  6. I would like to share my story in the context of this debate. Not because I dont think that anti-depressants have their role (because I do) but to highlight in my experience the role that chemical imbalances DO have on mental health.

    In my case I am extremely intolerant to histamines (which includes wide classes of drugs and foods). If I have histamines releasing drugs I become suicidal, mentally confused, and emotionally unstable within 24 – 48 hours.

    Dr Walsh (Pfeiffer Institute) has done a lot of research into chemical imbalances. Whilst I believe his research was relevant, and he helped diagnose me, I have chosen to go down a more traditional path and have been diagnosed and successfully treated by a professor of immunology and professor of pharmacology. My initially sceptical psychiatrist (‘it makes no medical sense’) is now sold as I became happy and stable within 48 hours of all drugs being withdrawn.

    I am told my situation is genetic – a gift from my keltish ancestors. Add to that post-partum depression, menopause, wilson’s disease to mention a few other known chemical imbalance and in my opinion there is enough pause for thought.

  7. I, too, completely agree with your article. Not only drugs for mental illness, but MANY MANY drugs are being pushed on the American (and other) public for little or no reason. The pharmaceutical companies do not care about the sick, they care about the profit. I agree that while short-term use can be helpful, there are a terrifying number of people taking unnecessary drugs when they could be benefiting from other forms of therapy.

  8. aged 23 I was diagnosed as having depression and have had it nearly every year since mostly in the winter but this year it has been a constant since january. My ex wife and a few trusted friends believe that I may actually be more bipolar as I have experienced brief periods of hyper enthusiasm and passion for life that are so out of normal character. They normally involve a number of ideas for businesses and a belief that I am suddenly well and will never be depressed or even unhappy again.

    During the last eight months I have contemplated ending my life many times as I am just fed up battling this state of mind which I believe is a result of not accepting the realities of life. I have pushed my GP to try and get an appointment with a Psychiatrist as my current medication appears to be of no use other than helping me get to sleep and I want to be properly assessed. I was hoping that medication for bipolar may be more beneficial buyt reading these threads I’m not encouraged.

    1. I’m not big on medications, as you’ve probably figured out. If you’re truly suicidal, that would be one of those cases where it might well be indicated, but you should also see a psychotherapist — someone who is going to talk with you about your experience — and not just someone who is going to evaluate you for meds.

  9. Psych meds,I say yes and no.Chemical imbalances,I’m not sure,maybe,it may depend on the person.I think it largely depends on the condition.Take schizophrenia,sometimes meds are all that will help to make the voices reduce/disappear,sometimes vitamins can help.Anxiety meds, I’ve been extremely helped by them,only problem now is the withdrawal.For mild to moderate depression I don’t agree with antidepressant use,I think as stated in the book “Healing without Freud or Prozac” & other books I’ve read : exercise,omega3 fatty acids,cardiac coherence,love,charity work,connecting to something greater than yourself,dawn simulation,EMDR,meditation,better communication and even hypnotherapy can be helpful.
    more details see link:

    I’ve suffered with severe clinical depression,tried 5HTP,St Johns Wort & an antidepressant (separately) none of them worked.Then a friend of a friend has a daughter who is bi-polar,she takes a vitamin supplement,she is living a much better life now,I go on this same supplement & I am getting my old self back,slowly but my friends & I can see the change.The funny thing is that I’ve taken other multivitamins & had blood tests for deficiencies that came out fine,I go on the supplement(EMPower Plus) ,2 months later I am a hell of a lot more stable,I eat,sleep better hours,have less suicidal urges,emotional pain,hospitalizations,crying & screaming “fits” all of which therapy didn’t help much at all & in some cases made me worse.Inositol (vitamin B8) helps with anxiety.I really hope more research will be done in the genetic vulnerabilities which may cause difficult nutrient use to nourish our brains causing depression & bi-polar so that psychiatrists will help people more effectively.After all isn’t lithium a mineral ? Maybe there are more chemical imbalances than just serotonin,or it is another system which we have not yet figured out? Nobody really knows exactly how lithium works,but who cares as long as it helps more than it hurts us,future research will probably tell us how.Whatever you choose to do,I wish you the best of luck. =)

  10. The video below contains some evidence for the effectiveness of antidepressants, and explanations for how they work. The lecturer is Robert Sapolsky of Stanford:

  11. Dear Dr. Joseph,

    Thank you for your response. I am a fan of your blog, although I disagree with some of your views.

    I can see a video on my screen, but clearly it does not show up in other people´s computers. I apologize for not doing due dilligence and checking this carefully. 🙂

    Here´s a how to get to the video:

    1) Youtube –> Stanford´s Sapolsky on Depression
    (the most relevant segment is between 14mins:25secs and 31mins:00secs)

    While I´m at it, here are a couple of other video references:

    2) Youtube –> Brain chemistry lifehacks: Steve Ilardi at TEDxKC
    (note that the speaker is advocating a type of essentially-but-not-necessarily med-free therapy)

    3) Youtube –> The most important lesson from 83,000 brain scans | Daniel Amen | TEDxOrangeCoast
    (most relevant segment: between 5mins25secs and 7mins:5secs)

    Both of the the above speakers both present evidence for “depression as a brain/brain chemistry theory” and warn about the limits dangers of medication-only treatment.

    I´m also at your disposal to present references to both books and research articles.

    Full disclosure: at this point I am very much in favor of the chemical-imbalance theory, but very much open to other approaches. Previously I did Lacanian therapy without taking medication and the result was ultimately disastrous. I am now both being treated by a “mindfulness-based” cognitive-behavioral therapist and taking medication under the guidance of a psychiatrist. The psychatrist communicates with the CGT therapist and vice-versa. Both agree that my condition results from a combination of brain disorders and environmental stressors, past and present.

    Finally, I apologize for the overly long reply. 🙂

    best wishes,


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