The Mind Fixers

(Originally published August 2019)

Anne Harrington is a Professor of the History of Science at Harvard University. Her recently published book, Mind Fixers: Psychiatry’s Troubled Search for The Biology of Mental Illness, is (by turns) an astonishing, sobering and appalling account of the treatment of mental illness during the past 160 years, and an articulate critique of the pretensions of biological psychiatry, past and present. According to Harrington, by the 1980’s “Irrefutable evidence that mental disorders were brain diseases had emboldened a new generation of biological psychiatrists to overthrow the Freudians and bring back the brain as the primary object of psychiatric research, diagnosis, and treatment. It was a simple explanatory story, one with clear heroes and villains and, above all, a satisfyingly happy ending. The only trouble with this story is that it is wrong, -- not just slightly wrong but wrong in every particular.”


Harrington is not a Freudian, nor does she question (per Thomas Szasz) whether some mental illness is a brain disease. However, she takes dead aim at the overweening pretensions of biological psychiatry, which she believes has limited understanding of the brain mechanisms leading to mental illness, and of the simple stories (such as correcting “chemical imbalances”) disseminated to the public to justify use of psychotropic medications. She asserts that “today one is hard pressed to find anyone knowledgeable who believes that the so-called biological revolution of the 1980’s made good on most or even any of its therapeutic and scientific promises. It is now increasingly clear …that it overreached, over-promised, over-diagnosed and over-medicated, and compromised its principles … there seemed to be little, if any sound biology undergirding the psychiatric enterprise.” Harrington insists that “we need a new story.”


The history of treatments of mental illness


Harrington begins by telling an old story in which truth is stranger than fiction. She maintains that early biological psychiatry (1880-1920) was focused on anatomy. “They had no understanding of the biochemical approaches that so animate our agendas,” she asserts.  Neurologists interested in mental illness were highly critical of lunatic asylums and their directors whom they believed were uninterested in understanding mental illness. Neurologists in this era advocated for transforming asylums into research centers. They were interested in studying the brains of deceased patients in search of anatomical abnormalities. After decades of acrimony and name calling between asylum directors and neurologists, Harrington asserts, “In the end, it all led to more or less nothing.” Critics of the anatomists such as Emil Kraepelin “believed that psychiatry, like every other branch of medicine, must identify specific diseases before it could do anything else. His colleagues needed to stop focusing on the brains of dead patients and start focusing on the symptoms of living ones.”


Based on surveys of large numbers of families of discharged patients, Kraepelin maintained that there were only two major kinds of psychoses, i.e., schizophrenia (referred to as dementia praecox), characterized by disordered perception and reasoning, and manic depression, a mood disorder. Kraepelin believed that schizophrenic patients did not improve and frequently deteriorated, while manic depressives (today’s bipolar disorder) often stabilized or improved. 


During the early 20th century, Kraepelin’s pessimistic prognosis for schizophrenics was replaced by what Harrington refers to as the

“Wild West” of extreme biological treatments:


  • removal of allegedly infected organs from the bodies of schizophrenic patients: teeth, appendixes, ovaries, testes “and more”;

  • mandatory sterilization of the “feeble minded” tied to genetic explanations of mental illness and other conditions;

  • electroconvulsive therapy, still used today to treat depression;

  • malaria fever treatment in which patients diagnosed as having General Paralysis of the Insane (GPI) were deliberately infected with malaria and then treated with quinine; some clinicians used a small number of psychiatric patients as “malarial reservoirs” by repeatedly infecting them with malaria … “so the clinicians could use their contaminated blood.”

  • insulin induced comas;

  • Metrazol shock treatment in which epileptic type seizures were deliberately induced;

  • lobotomy, i.e., the deliberate surgical destruction of brain tissue in the frontal lobe; eventually transorbital lobotomies were performed by use of a “pick” to penetrate a patient’s brain via the eye socket.


Each of these treatments had an underlying theoretical rationale, and all (except sterilization) initially led to impressive, in some instances quasi-miraculous results, until negative outcomes were gradually discovered, a pattern that has persisted during recent decades of claims for the benefits of various drugs. For example, a 1938 study of 1000 patients who received insulin shock treatment found that “eleven percent of schizophrenic patients … were said to have completely recovered, 26.5 percent were declared greatly improved, and another 26 percent were said to show evidence of some improvement.” In 1958, the British psychiatrist, Harold Borne, claimed that “insulin coma treatment was - and always had been – an ineffective biological treatment but, ironically, a rather effective psychological one,” i.e., “the special attention given to patients undergoing the treatment likely did them considerable good,” a conclusion that called into question the pretension of biological psychiatrists to have discovered the brain mechanisms involved in chronic mental illness.    


Two developers of treatments in the list above, Julius Wagner-Jauregg and Egas Moniz, won the Nobel Prize in Physiology or Medicine, Jauregg-Wagner in 1927 for his work in developing malarial fever treatment and Moniz in 1949 for “pioneering the use of lobotomy in relieving certain kinds of mental illness,” despite the ethically repugnant nature of these treatments. Biological psychiatry in the early 20th century was ethically challenged (to put it mildly) by the support of some of its proponents for eugenics, mandatory sterilization of the “feeble minded” and even euthanasia. It would be difficult to overestimate the corrupting influence of various kinds of economic support provided by drug companies to many biologically oriented psychiatrists during the past several decades.        


Early drug treatment of schizophrenia 


In 1954, the Food and Drug Administration approved the use of chlorpromazine, aka, Thorazine, for the treatment of schizophrenia.

According to Harrington, “in the early years, many clinicians described this new drug as a “chemical lobotomy” because “it accomplished many of the therapeutic and managerial goals of the lobotomy, but in … far less destructive ways.” Initially, Thorazine was viewed as a miracle drug that allowed a chronically mentally ill person to live outside mental hospitals. Harrington quotes a 1956 ad in a trade journal: “Disturbed wards have virtually disappeared.” She asserts that “Within ten years of approval, some fifty million prescriptions had been filled.” However, she writes that “By the 1960’s … the initial high hopes for what anti-psychotic drugs would accomplish had been significantly dampened.” These drugs were “often effective in reducing delusional thinking and hallucinations – the so-called positive symptoms of schizophrenia … (but) had little effect on the so-called negative symptoms: lack of motivation and problems in interpersonal relations.” In addition, “Side effects ranged from chronic nausea to a sense of restlessness that some described as wanting to crawl out of one’s skin. Many also gained a lot of weight, and a significant number also developed tardive dyskinesia, a neurological disorder that causes abnormal limb movements, disabling facial twitches, and tongue protrusions, usually permanently …”  Some patients developed a Parkinson’s like side effect, “a strange shuffling way of walking” that came to be known among psychiatrists as the “Thorazine shuffle,” Harrington states. 


Second generation, “atypical” anti-psychotic drugs


Harrington description of the development and use of second generation antipsychotic drugs between 1975 and the early 1990’s has many of the same elements as her chapter on Thorazine. One of the first of these new antipsychotics was Clozapine which “did not seem to cause extrapyramidal side effects (twitching, restlessness, Parkinson’s like forms of motor retardation, etc.).” In controlled trials, “Clozapine came out squarely ahead,” of Thorazine with positive effects on both the active symptoms of schizophrenia and the “negative symptoms,” e.g., withdrawal, apathy.  Other copycat atypical anti-psychotics quickly came on the market; Risperdal, Zyprexa, Seroquel and Abilify. To increase sales, drug companies marketed these new miracle drugs for treatment of not only schizophrenia but also bi-polar disorder, depression and problems with dementia, as well as “a non-specific treatment for moodiness, irritability and insomnia,” Harrington maintains.


However, documents leaked to the New York Times in 2006 revealed that one of the drug companies, Eli Lilly, “had actively downplayed or buried evidence showing a strong link between Zyprexa and medication induced obesity, high blood sugar, and diabetes. According to Harrington, “By 2007, Eli Lilly had paid at least $1.2 billion to settle lawsuits involving 28,500 people who claimed to have developed diabetes or other disorders after taking Zyprexa.”


Harrington acknowledges that second generation anti-psychotic drugs had tremendous positive benefits for some people while harming others. Some persons experienced both great benefits and great harm. In 2006, the New York Times published the following letter to the editor:


"Zyprexa is a miracle drug for some of us … it opened up the world, allowed me to read and feel a crackling enthusiasm for life for the first time in years, and it cut down drastically on the voices and strange thoughts.


Zyprexa was also the worst drug I’ve ever taken, making me gain 65 pounds and adding 100 points to my cholesterol, and raising my   triglycerides sky-high. I was both ecstatic to be involved in the world and miserable, obese and unhealthy. … I now take three different antipsychotics that are effective but not as miraculous.


I miss Zyprexa."  




Harrington’s account of the development of anti-depressants has the same general features as her summaries of biologically based treatments for schizophrenia:


  1.  A straightforward theoretical rationale based on hypotheses regarding the effects of specific neurotransmitters such as serotonin and norepinephrine on depressed moods;

  2.  Early success in controlled trials leading to heightened expectations of an actual cure for depression;

  3.  Growing awareness of negative side effects associated with prolonged use;

  4.  Disillusionment with the whole enterprise, bitterness directed at psychiatrists who prescribed these drugs and skepticism regarding the underlying scientific rationale(s).


Some readers may remember Peter Kramer’s book , Listening to Prozac  (1993), in which Kramer, a psychiatrist, suggested that Prozac was not only an effective treatment for depression, but also a performance enhancing drug that could transform formerly troubled people into confident, relaxed and more attractive people. Harrington writes: 

“In a remarkable sentence … (Kramer asked) “Who was I to withhold from her (one of his patients who was not depressed) the bounties of science.” Prozac became the best-selling antidepressant of all time.


However, according to Harrington, “It was not all good news for Eli Lilly. In … 1990 the company found itself facing a first slew of lawsuits that suggested Prozac might not be as safe as all that, after all. Pointing to research spearheaded by the Harvard psychiatrist, Martin Teicher, the plaintiffs argued that Eli Lilly had suppressed evidence that the drug was capable of sparking violent or suicidal behavior in a fraction of patients who had never previously acted that way.” This lawsuit was settled out of court. Harrington states that “the drugs (selective serotonin re-uptake inhibitors, aka SSRI’s) remained widely used, but with greater awareness that they did not always work, that they did not work forever, and that taking them was not without risk.” She might have added that people taking the drugs for long periods of time often had great difficulty discontinuing their use, even when they were experiencing serious side effects, a subject I will discuss in next month’s Sounding Board.    


In recent decades, Harrington asserts, it has become difficult for drug companies to demonstrate in controlled trials that anti-depressants work better than placebos. Harrington summarizes a 1998 meta-analytic study in which “patients in the active treatment group did only marginally better than those in placebo groups. She asserts that “some 75 percent of the improvement seen in people taking the active medication could be attributed to the placebo effect.” Two researchers, Kirsch and Sapirstein, stated in the report of their meta-analysis that “they had “listened” to Prozac, then realized they were actually “hearing” placebo,” Harrington states.  


Is there a new story of mental illness?


Harrington clearly believes that recent stories promulgated to justify drug treatments of mental illness are as mistaken as old stories of brain infections used to justify extraction of teeth and surgical removal of the colons of schizophrenics. She is caustic in her comments regarding claims that antidepressants correct “chemical imbalances” in the brain.

She asserts that  “… general practitioners and psychiatrists perpetuate the fictions that the drugs they are prescribing are correcting biochemical deficiencies caused by disease, much as … a prescription of insulin corrects a biochemical deficiency caused by diabetes.” Nevertheless, Harrington maintains that some people who suffer from “mental affliction” are “(almost certainly) suffering from a real illness, one that is understandable (in principle) like any other medical complaint. … others are (almost certainly) not.” This perspective resembles the distinction popularized by E. Fuller-Torrey (author of Witchdoctors and Psychiatrists) in the 1970’s between mental health conditions which are brain diseases, i.e., schizophrenia, and “problems of daily living.” Torrey’s distinction is appealingly simple, but also clearly wrong.


Depression, “the common cold” of mental health problems, appears to have a biological component, and is greatly affected by intra-psychic processes such as negative self-talk. Depression also has a social dimension in the relative powerlessness of high-risk groups such as women, the elderly and low-income adults. If depression (and its frequent companion, anxiety) is not a “problem of living,” nothing is.


If schizophrenia is a brain disease (as seems likely), it’s onset, course of illness and treatment outcomes are nevertheless influenced by social factors and interpersonal relationships. No bright line between mental health conditions resulting from brain disease and those which are “problems of living” is likely to be discovered, for the reason described by Harrington:


“…people are not engineered systems that can absorb only so much load before they collapse; they are thinking organisms who appraise their situation and figure out whether or how they can cope with it.”


A new plausible story of mental illness must speak cogently to the interactions between biology/brain, intrapsychic processes and the social environment. Harrington, despite her encyclopedic knowledge of mental health treatments and astute judgment, does not offer a suggestion of what this story might be.




Harrington, Anne, Mind Fixers: Psychiatry’s Troubled Search for The Biology of Mental Illness, W.W. Norton & Co., 2019.  


Torrey, E. Fuller, Witchdoctors and Psychiatrists: The Common Roots of Psychotherapy and Its Future, Harper and Row, New York City, 1972.       


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