Editor’s Note: Over the next several months, Mad in America is publishing a serialized version of Peter Gøtzsche’s book, Critical Psychiatry Textbook. In this blog, he discusses the failures of the publicly funded long-term studies, CATIE and STAR*D, and psychiatry’s fraudulent reporting of these results. Each Monday, a new section of the book is published, and all chapters are archived here.
The disappointing CATIE and STAR*D studies
The two sane authors of the first chapter of the 1065-page textbook noted that naturalistic studies—which they did not reference but mentioned by name, CATIE, STAR*D, and Storebø 2016—have shown smaller effects than those the drug companies have advertised.17:57 They also said that psychiatry is plagued by a bad reputation after cases of overmedication and that more caution is needed when using psychiatric drugs.17:58
For CATIE, there were 191 records on PubMed. It was an NIMH-financed trial, which randomised 1,493 “real-world” patients with schizophrenia to olanzapine, quetiapine, risperidone or ziprasidone, or to a very old drug, perphenazine, marketed in 1957.
The results must have agonised the key opinion leaders in psychiatry. The primary outcome was very reasonable, time to discontinuation for any reason, which reflects both the benefits and the harms of the drugs. After 18 months, only 26% of the patients were still on the randomised drug, and perphenazine was not worse than the “atypicals” and did not produce more extrapyramidal harms than these agents.239
So much for the highly praised “modern” psychosis pills, which are far more expensive than a 65-year-old drug off patent. But psychiatry’s narrative was not affected. The study authors talked about the comparable levels of effectiveness of the five drugs,239 but they should have talked about comparable levels of ineffectiveness, as all the drugs failed according to the primary outcome. Psychiatrists are masterminds in this type of semantic deception.
STAR*D was also financed by the NIMH. It is a remarkable story of fraud.7:118 Like CATIE, it was a highly relevant study of real-world patients. With 4,041 included patients,647 it is the largest effectiveness study ever conducted of depression pills. The investigators announced that the study would produce results with “substantial public health and scientific significance,”647 which it did, but not in the way they had imagined.
There was no placebo group, and all patients started on citalopram, manufactured by Lundbeck, which was motivated by horrendously erroneous claims of citalopram’s “absence of discontinuation symptoms” and its “safety” in elderly patients. In their disclosure statements, 10 of STAR*D’s authors reported receiving money from Forest, Lundbeck’s partner in the United States.
When the study was over, NIMH announced falsely that “about 70% of those who did not withdraw from the study became symptom-free.” The investigators also made numerous false claims, e.g. that the patients who scored as remitted had “complete absence of depressive symptoms” and had “become symptom-free.” The truth was that a “remitted” patient could have a Hamilton score of 7. The only Hamilton suicide question, “feels like life is not worth living,” is scored as 1, and other symptoms that are scored as 1 include “feels he/she has let people down” and “feels incapable, listless, less efficient.” No honest professional would describe such patients as having become symptom-free.
The researchers noted in their abstract that, “The overall cumulative remission rate was 67%.” In the main text, however, they said that this was a “theoretical” remission rate assuming that those who exited the study would have had the same remission rates as those who stayed in the protocol. That assumption is extremely unlikely to be true. There are usually many more treatment failures among those who drop out than among those who continue.
The investigators cherry-picked the data they reported. This involved the Texas sharpshooter trick (see Chapter 6) by changing the measurement scale. They also included patients that, according to the protocol, should have been excluded. This, the French call “sauve qui peut” (save those you can), which characterises a state of panic or disorder.
The data were presented in such a confusing manner that it is extremely difficult to correct for all the errors and find out what really happened, even for a seasoned research detective like me. Ed Pigott et al. did the hard detective work for us.647 It turned out that only 3% of the patients who entered the trial remitted, stayed well, and stayed in the trial during the one-year follow-up!
This publicly funded study bombarded doctors and the public with the totally mendacious message that depression pills enable about 70% of depressed outpatients to recover. The medications were said to be “far more effective” than placebo, which was also mendacious, as there was no placebo group in the trial.
A journalist interviewed one of the STAR*D investigators, Maurizio Fava, a prominent psychiatrist, who acknowledged that the 3% success rate was accurate and that the investigators knew this all along.648
The many STAR*D papers display highly selective reporting of outcomes, numerous false claims, contradictory statements, and even pure fiction. As of mid-2011, despite over 100 papers having been published, 11 prespecified outcomes had still not been reported.147 One paper stated in the abstract that suicidal ideation was seen in only 0.7% of the patients, and the authors said that their study “provides new evidence to suggest little to no relation between use of a selective serotonin reuptake inhibitor and self-reported suicidal ideation.” This statement was contradicted by some of the same authors who, in other papers, mentioned suicidal ideation in 6.3% and 8.6% of those on citalopram in STAR*D, i.e. 10 times more.
It is remarkable that suicidality can differ by a factor of 10 or more in different publications of the same trials, but this was also the case when the FDA investigated this issue (see Chapter 8, Part Six).
The STAR*D study is so fraudulent that all its 100+ papers should be retracted. Ed Pigott says about this:649
“In my five plus years investigating STAR*D, I have identified one scientific error after another. Each error I found reinforced my search for more … These errors are of many types, some quite significant and others more minor. But all these errors—without exception—had the effect of making the effectiveness of the antidepressant drugs look better than they were, and together these errors led to published reports that totally misled readers about the actual results. As such, this is a story of scientific fraud, with this fraud funded by the National Institute of Mental Health at a cost of $35 million.”
I could not find any naturalistic study published by Storebø in 2016. The textbook authors might have referred to his 2015 Cochrane review, which found that every single trial ever performed of stimulants in children with an ADHD diagnosis was at high risk of bias.511
Thomas Insel and the NIMH: A total betrayal of public trust
Thomas Insel, called “America’s psychiatrist,” was director of the NIMH for 13 years, till 2015.650 In 2022, he published the book, Healing: Our Path from Mental Illness to Mental Health.651
The book makes an unintended case for abolishing psychiatry even though Insel tries to support it.650 He takes on the role of a drug salesman, and already the title is misleading. There has been no path from mental illness to mental health, only one to even more mental illness.
Insel is aware of this and promises to investigate why mental health outcomes in the United States are so poor. The publisher presents the book as a roadmap for change, but this is not what it is about; in fact, Insel shies away from suggesting what is so obviously needed.
Coming from the most prestigious institution in the world in mental health, it is worth looking more closely at this book, as it reflects the thinking of psychiatric leaders all over the world. This is what Robert Whitaker did in his book review.650 The book encapsulates how psychiatry has consistently betrayed public trust and misinformed the public. It underlines that psychiatry will never tell the public the truth about psychiatric drugs, and Whitaker concludes that the real source of the poor mental health outcomes in the United States is the psychiatric establishment, including the NIMH, which—although being a governmental agency—cannot be trusted.
Being a former NIMH director, Insel should have told his readers about the poor long-term outcomes of treatment with psychiatric drugs, as documented in expensive and prestigious research funded by the NIMH, e.g. CATIE and STAR*D. He didn’t, even though he had an obvious ethical obligation to do so.650 Whereas drug companies have funded the short-term studies of drugs, it was the NIMH, dating back to the 1970s, that funded studies of their long-term effects.
This made it even more deplorable that Insel avoided commenting on them. The public expects that a medical specialty will be an honest purveyor of scientific findings about the benefits and harms of its interventions, and if its research tells of treatments that worsen long-term outcomes, then the medical specialty will inform the public of those outcomes and rethink its practices.
For 65 years, psychiatry has failed to do this. Insel could have remedied this betrayal of public trust with this book and put psychiatry on a new path, but he sacrificed the patients and protected the psychiatric guild by keeping the long-term studies hidden.
When Whitaker wrote his book, Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America, first published in 2010,5 he started out with a medical puzzle.
The conventional history of psychiatry tells of how the introduction of psychosis pills in 1954 kicked off a psychopharmacological revolution, which was said to take another step forward with the SSRIs in 1988. The prescribing of psychiatric drugs soared, but why did the burden of mental illness soar, too? According to Insel, the number of adults in USA receiving a social security payment due to a mental disorder rose from around 1.3 million in 1987 to around 6 million today.
Whitaker dug through the research literature, and with each class of drugs, he tried to find out what the clinical course was before and after the introduction of drugs, and if the medicated or unmedicated patients had better long-term outcomes in clinical studies. Whitaker found that psychosis pills, depression pills and benzodiazepines worsen long-term outcomes, and that bipolar disorder, which is regularly treated with polypharmacy, runs a much more chronic course than manic depressive disorder—the diagnostic precursor to bipolar—once did.5
Whitaker is a careful researcher and his book is highly convincing. There was a great deal of pushback from prominent American psychiatrists when it came out but when a filmmaker inter-viewed Insel five years later and asked him about Whitaker’s book, he responded that Whitaker’s observations needed to be taken very seriously and noted that, in other areas of medicine, if you increase the use of your medication several times, you will see reductions in morbidity and mortality.
This short glimpse of sanity in psychiatry quickly disappeared. Insel asked the right question in the first chapter of his book:650
“When it comes to mental illness, there are more people getting more treatment than ever, yet death and disability continue to rise. How can more treatment be associated with worse outcomes?”
But he didn’t give the right answers. In a most appalling fashion, Insel dismissed any worry that psychiatric drugs could be the cause of the poor outcomes. He used the tactic philosopher Arthur Schopenhauer calls making a diversion (see Chapter 4). Insel suddenly began talking of something else, as though it had a bearing on the matter. He wrote that Whitaker argues that drugs against depression and psychosis create a “supersensitivity” that makes patients dependent and chronically disabled. This is a red herring. Whether supersensitivity occurs or not (which I believe it does; see also below) is immaterial for Whitaker’s convincing findings.
Insel claimed that Whitaker writes that the psychiatric establishment, in collaboration with the pharmaceutical industry, has conspired to overmedicate and overtreat children and adults with disastrous results, and that not everyone buys this conspiracy theory.
This is mendacious. The only time Whitaker used the term conspiracy was when he quoted a patient with schizophrenia who spoke about conspiracies.5:21 Insel used the diversion trick again and another of Schopenhauer’s tricks: “Postulate what has to be proven.”83
Insel turned sand into gold by making yet a third horrific diversion. He claimed that current treatments are necessary but not sufficient to cure complex brain disorders. This has absolutely no bearing on the case. He quoted his predecessor Steven Hyman who said we need to know much more about the biology of mental illness before we “can illuminate a path across very difficult scientific terrain” and develop medications that are as effective as insulin or antibiotics.
The pompous mumbo jumbo covered up for the fact that biological psychiatry is a total failure, which history has so clearly shown. Furthermore, Insel’s ill-founded fantasies about a better future do not remove the immense harm his specialty currently inflicts on hundreds of millions of people.
Insel went further into adventure land. He thinks clinicians are more effective today than they were 25 years ago. Indeed. They are harming their patients more than ever!
Insel’s diversions multiplied. He noted that most people with mental illness are not treated; that many of those receiving drugs do not take them; and that patients receive little more than drugs. He cleverly put the blame for the poor outcomes on society for not investing in necessary social supports and on patients for failing to take their drugs and stay engaged in treatment.
This is the standard script for psychiatrists. The disaster they have created is not their fault. Others are to blame, including the patients and society. But if more patients took their drugs, the disaster would only be worse.
Nothing in Insel’s narrative would harm psychiatry’s guild interests or pharmaceutical interests. Insel described himself as taking on the role of a journalist as he explored humanistic supports that are needed to complement drugs to promote lasting recovery.
This is a win-win position to take. Anyone will welcome social support. Critics of psychiatry have advocated for such efforts for decades, and Insel now positioned himself as the advocate for this societal response. This was manipulation at the highest level. With that framework in place, there would be no place in his 300-page book for research that told of drug treatments that worsen long-term outcomes.
Instead of criticising the drugs, Insel praised them. In the chapter “Treatments Work,” he claimed that psychiatric drugs, ECT, and transcranial magnetic stimulation work and that depression pills have an effect size as high and often higher than medications used in other areas of medicine. A remarkable statement about drugs that have no clinically relevant effects. My comment on this type of argument is that one unlawful parking does not make the next parking lawful. There are many ineffective drugs in medicine that should not be used.
Insel didn’t cite a single study that told of psychiatric drugs providing a long-term benefit. This glaring omission leads to the conclusion that the former director of the NIMH is unable to find a single study to cite that told of a drug improving long-term outcomes. Insel’s book is a superb example of The Emperor’s new clothes. The Emperor is totally naked but so well dressed up that few readers will notice it.
In his book review, Whitaker provided a summary of studies Insel did not dare mention.650 In the next chapter, I will present a brief of this summary. The links to the papers can be found in the original, which is open access, and in my reference list.
To see the list of all references cited, click here.
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