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 many studies finding poor long-term results with psychiatric drugs and how the drugs lead to a more chronic course for depression and psychosis. Each Monday, a new section of the book is published, and all chapters are archived here.
After psychosis pills were introduced in the mid-1950s, clinicians began speaking about the “revolving door syndrome” that now appeared in asylum medicine. First-episode patients would be discharged and then return in droves, which led the NIMH, during the 1970s, to fund four studies to assess whether psychosis pills were increasing the chronicity of psychotic disorders.
Bockoven652 reported that the rehospitalisation rate for discharged patients was higher for patients treated after the arrival of psychosis pills and the medicated patients were also more “socially dependent” than those treated before 1955. Carpenter,653 Mosher,654 and Rappaport655 reported superior outcomes for unmedicated patients after 1-3 years, which led Carpenter to “raise the possibility that antipsychotic medication may make some schizophrenic patients more vulnerable to future relapse than would be the case in the natural course of the illness.”
By this time, researchers were fleshing out the adaptive brain changes stirred by psychosis pills. Chouinard concluded that drug-induced dopamine supersensitivity “leads to both dyskinetic and psychotic symptoms. An implication is that the tendency toward psychotic relapse in a patient who has developed such a supersensitivity is determined by more than just the normal course of the illness.”656 This understanding of how the brain adapts to psychosis drugs provided a biological explanation for why drug treatment increased the chronicity of psychotic disorders and a causal explanation for the findings reported by Bockoven, Carpenter, Mosher and Rappaport.
Nancy Andreasen, also funded by NIMH, reported in a large MRI study of patients with schizophrenia that psychosis pills shrink brain volumes over time,63 and that this shrinkage is associated with a worsening of negative symptoms, increased functional impairment, and, after five years, cognitive decline.657
In the late 1970s, with funding from the NIMH, Martin Harrow and Thomas Jobe launched a long-term study of 200 patients diagnosed with schizophrenia or other psychotic disorders, most of whom were experiencing a first or second episode of psychosis. They found that the outcomes of those who got off their psychosis pills by year two began to dramatically diverge from those who stayed on the drugs, and that at the end of 15 years, the recovery rate for the off-med patients was eight times higher than for the medication compliant patients (40% versus 5%).658 They also reported that the medication compliant patients were much more likely to remain psychotic over the long term than those who got off the medication, and it was the off-medication patients who had dropped out of treatment that had the better outcomes.659 They referred to drug-induced dopamine supersensitivity as a likely reason for this difference in outcomes.
In the past two decades, longer term studies of psychotic patients conducted in the Nether-lands (the only long-term randomised trial of drug discontinuation, see Chapter 7, Part Four),192 Finland,660 Australia,661 Denmark,662 and Germany663 all told of higher recovery rates for those off drugs. Similarly, users of psychosis pills tell of how these drugs compromise functional recovery over the long-term.664
The history of depression pills is much the same. Prior to their introduction, depression—and this finding came from studies of hospitalised patients—was understood to be an episodic disorder. Patients could be expected to recover, and around half of the patients who suffered a first episode would never be rehospitalised for depression.
After the introduction of depression pills, some clinicians observed a “chronification” of the depression. In the 1980s, several studies found high relapse rates in patients treated with depression pills, and an expert panel convened by the NIMH concluded that, in contrast to older studies of mood disorders, “new epidemiological studies [have] demonstrated the recurrent and chronic nature of these illnesses.”665 The elephant in the room was ignored.
Two NIMH studies in real-world patients treated in outpatient settings confirmed that this was the long-term course for medicated patients. The STAR*D trial,647 with its 3% stay-well rate at the end of the one-year follow-up on depression pills stood in sharp contrast to another NIMH funded trial that sought to identify the long-term outcome of untreated depression in recent times. In that study, 85% of the included 84 patients had recovered by the end of one year.666 The researchers concluded that “If as many as 85% of depressed individuals who go without somatic treatment spontaneously recover within one year, it would be extremely difficult for any intervention to demonstrate a superior result to this.”
Many studies over the past 35 years have compared outcomes for medicated and unmedicated patients over longer periods of time.
In an NIMH study that randomised 250 patients to imipramine or to two forms of psychotherapy or to placebo, the stay-well rate was highest for cognitive therapy (30%) and lowest for imipramine (19%) and placebo (20%) after 18 months.667
In an NIMH study of 547 patients that compared six-year outcomes for depressed people treated for the disorder and those who eschewed medical treatment, the treated patients were three times more likely than untreated ones to suffer a cessation of their principal social role and nearly seven times more likely to become incapacitated.668
A WHO study of 640 depressed patients found that those treated with medication had worse general health and were more likely to still be mentally ill than those who weren’t treated at the end of one year.669
A Canadian study of 1,281 people who went on short-term disability due to a depressive episode found that 19% of those who took a depression pill went on to long-term disability compared to 9% of those who never took such medication.670
In a five-year study of 9,508 depressed patients in Canada, medicated patients were depressed on average 19 weeks a year, versus 11 weeks for those not taking drugs.671
Two reviews of the long-term outcomes of patients diagnosed with depression found that use of a depression pill was associated with worse outcomes at nine years672 and at 30 years.673
As these findings have piled up, researchers—led by Italian psychiatrist Giovanni Fava—have pointed to drug changes induced by depression pills as a likely explanation for the “bleak long-term outcome of depression … use of antidepressant drugs may propel the illness to a more malignant and treatment unresponsive course.”674-677
In a 2011 paper, American psychiatrist Rif El-Mallakh observed that 40% of depressed patients initially treated with a depression pill were now ending up in a chronically depressed “treatment resistant” state.678 He wrote that continued drug treatment may induce processes that may “cause a worsening of the illness, continue for a period of time after discontinuation of the medication, and may not be reversible.”
Given this literature, it is no surprise that depression is now the leading cause of disability in the United States for people ages 15 to 44, and that in country after country that has adopted widespread use of SSRIs, the number of people on government disability due to a mood disorder has increased in lockstep with the increased use of these drugs.119:24
Whitaker also mentioned the MTA trial (see Chapter 9, Part Two). The investigators noted that, at the end of three years, being on a stimulant was a significant marker not of beneficial outcome, but of deterioration.517 At the end of six to eight years, the results were much the same.521 Longer-term ADHD studies in Australia679 and Quebec680 also found worse outcomes for medicated youth than for those treated without stimulants.
As Whitaker noted, the research literature shows that psychosis pills and depression pills increase the chronicity of the disorders, and the same is true for stimulants, benzodiazepines, and drugs used for bipolar disorder. He also mentioned that a longer list of over 100 papers that tell of these outcomes can be found on the Mad in America resource pages for psychosis pills, depression pills, benzodiazepines, polypharmacy for bipolar disorder, and stimulants.650
None of this history is found in Insel’s book or on NIMH’s website.650 A search for Martin Harrow shows nothing even though he was considered one of NIMH’s experts on schizophrenia. A search for STAR*D shows the press release about the short-term results that tells of “particularly good results” with depression pills that “highlight the effectiveness of high-quality care.”681 The one-year stay-well rate for patients treated with depression pills of 3% is missing (that information was hidden in the journal article that reported one-year outcomes648). And the NIMH website information about ADHD682 does not inform parents that in the MTA study, medication use was a marker of deterioration by the end of year three, and that those taking stimulants had worse ADHD symptoms and were more functionally impaired at the end of six years.
The chemical imbalance myth is derided as a hypothesis that fell out of favour97 decades ago, with Ronald Pies, former editor in chief of Psychiatric Times, describing it as an “urban legend” that was never “seriously propounded by well-informed psychiatrists.”97 Allen Frances,683 and other prominent figures in the field, including Insel684 and his predecessor Steven Hyman,685 acknowledge that the disorders in the DSM manual have never been validated as discrete illnesses, and that the diagnostic categories are constructs. In his book, Insel admits that the so-called second-generation psychiatric drugs are no better than the first, the notion that they were “breakthrough medications” having been put to rest some time ago.
In 2015, Whitaker and Lisa Cosgrove published Psychiatry Under the Influence,599 a book that arose from their time as fellows at the Safra Center for Ethics at Harvard University, in a lab devoted to studying institutional corruption. In a democratic society, the expectation is that institutions that serve a public interest—and this is particularly true for medical disciplines—will adhere to ethical standards. This includes rising above financial influences; being objective in their design of studies and their analysis of the data; reporting the results in an accurate and balanced way; and putting the interests of patients first.
In a 2009 essay,686 Daniel Wikler, a professor of ethics at the Harvard School of Public Health, wrote that a medical discipline that fails to adhere to this standard doesn’t deserve to retain its privileged place in society.
On Whitaker’s Mad in America website there are two more reviews of Insel’s book.650 These reviews also describe how the book functions as a work of propaganda for a sick system.
The erosion of medical integrity is complete for psychiatry1-11,533 and the psychiatric narrative has collapsed. Yet, drug prescribing increases. If the psychiatric profession told the public the truth, psychiatry would have to completely reorganise its care.
As Whitaker wrote,650 this is the bridge that psychiatry, as a guild, cannot cross. The profession needs to keep the truth out of sight, even to itself, and it is not presented in psychiatric textbooks or in continuing medical education seminars. By keeping the history hidden, the field is breaking its compact with the public and itself—with every prescriber and all those who enter the field.
A 2022 misleading seminar in The Lancet about suicide
A recent Lancet seminar was yet another proof that psychiatry has degenerated to a point from which there is no return. Honest information about suicide is of utmost importance but the article Lancet published, “Suicide and Self-harm,”687 was dishonest.
The seminar was very long, 14 pages, with 142 references. Many people consider Lancet a highly prestigious and influential journal, which should therefore be open to criticism and debate. But it isn’t. A journal that does not accept letters for publication unless they arrive within two weeks of publication of the original item and unless they are no longer than 250 words does not invite criticism and a sound scientific debate. Many people will not know that an article has been published before it is too late to criticise it.
The Lancet seminar is one of the most misleading articles about suicide I have ever seen.688 The authors wrote that research has identified “associations between suicidal behaviour and dysregulation of the hypothalamic–pituitary–adrenal axis and serotonergic neural transmission.”
They tried to resurrect the stone dead myth about a chemical imbalance in the brain being the cause of psychiatric disorders, and the two references they cited are untrustworthy (see Chapter 4). The first alluded to epigenetic modification of genes, alterations in key neurotransmitter systems, inflammatory changes, and glial dysfunction in the brain as causal factors. The second suggested hypothalamic-pituitary-adrenal axis dysfunction, which “in turn can be traced back to genetic predisposition” and “early life stress-related epigenetic mechanisms.”
Among risk factors for suicide, the authors mentioned “harmful substance use” but not depression pills, antiepileptics, or the psychiatric profession itself. These are taboos for suicide researchers.
The authors wrote that “The use of medication to prevent suicide is controversial” and that there is a “possibility of exacerbating suicidal thoughts, particularly in young people.”
As I have explained in my book, it is seriously dishonest to speak about a “possibility of exacerbating suicidal thoughts.” These drugs not only exacerbate suicidal thoughts, they cause them, and they also cause suicidal behaviour, suicide attempts, and suicide.
The seminar authors did not quote any of the many meta-analyses of placebo-controlled trials that showed that depression pills increase the suicide risk. Instead, they quoted a book written by the last author of the seminar and by Robert D Goldney who has published a fatally flawed review about depression pills and the risk of suicide.689
His paper is a classic example of how one should not do a review.7:100 He cherry-picked those observational studies that supported his idea that depression pills protect against suicide, e.g. studies in the Nordic countries that linked prescribing of depression pills with a reduction of suicide, but these studies are untrustworthy.7:97 Nordic researchers have shown that there is no statistical association between the increase in sales of SSRIs and the decline in suicide rates in the Nordic countries.690 They reported that the decline in suicides in Denmark and Sweden predated the introduction of SSRIs by 10 years or more.
The Nordic researchers had no conflicts of interest while Goldney had “received honoraria and research grants from a number of pharmaceutical companies.” With his flawed reviews, Goldney must be worth far more than his weight in gold for the drug industry.
The seminar authors wrote that “treatment of underlying psychiatric conditions through medication can reduce suicidal behaviour.” They gave no references to this information. Which are the miraculous drugs that can reduce suicides? All we know is that psychiatric drugs increase suicides.
A little later, they wrote: “Evidence from several studies, most of which were observational, suggests that antidepressants might reduce the risk of suicide.” They used the UFO trick. They quoted a 2021 review that reported that meta-analyses had found that “antidepressants prevent suicide attempts, but individual randomized controlled trials appear to be underpowered.”691 These meta-analyses were of observational studies. All meta-analyses of randomised trials have shown the opposite and they are not underpowered.
In the next sentence, they wrote: “However, some research has found an association with increased risk of suicide-related outcomes in young people.” This is also blatantly false. When the FDA looked at all relevant research, not just some research, and indeed the best we have, the randomised placebo-controlled trials, it was a causal relation and not just an “association.”
In the ensuing sentence, they wrote: “The evidence base is far from complete, since many randomised trials exclude people at heightened risk of self-harm or suicide.” This is utter nonsense. We have all the data we need to conclude that depression pills double suicides. The authors used the familiar trick Schopenhauer calls diversion by suddenly talking of something else that has no bearing on the matter.
The authors claimed that “Lithium has been associated with reduced suicide rates in people with bipolar disorder and depression, which might be a specific effect not seen with other drugs designed to stabilise mood.” As noted earlier (see Chapter 8, Part Ten), there is no reliable evidence that lithium reduces suicides.
About the latest fad in psychiatry, the authors wrote that “Ketamine has shown promise.” It hasn’t (see Chapter 8, Part Three).
There was a glimpse of light in all the psychiatric darkness. The authors wrote that “cognitive behavioural therapy and related treatments have the strongest evidence base for reducing suicidal ideation and repeat self-harm compared with treatment as usual.”
This is correct, but they quoted a review that included self-harm. Self-harm does not always imply a suicidal intent. My research group therefore did a systematic review where we excluded self-harm studies. We found that psychotherapy halves the risk of a new suicide attempt in people acutely admitted after a suicide attempt.272 Our review was published in 2017 in a well-known journal but was not among the seminar authors’ 142 references even though it sends a very strong message: Do not use pills but psychotherapy if you want to prevent suicide.
Lancet is not the source to go to if one wants reliable information about depression pills. It is the extended marketing arm of the pharmaceutical industry,692 just like the New England Journal of Medicine is, also in relation to articles denying that depression pills cause suicide.337
To see the list of all references cited, click here.
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