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 damage psychosis pills cause to the brain, and how that manifests in many clinical harms, like tardive dyskinesia. Each Monday, a new section of the book is published, and all chapters are archived here.
Irreversible brain damage and other serious harms
The textbooks provided contradictory information about irreversible brain damage, and one tried to explain it away in a most confusing fashion.16:222 It noted that psychosis pills probably prevent loss of brain tissue in many patients, but that a harmful effect in others cannot be excluded.
It has not been documented that psychosis pills can prevent brain damage and evidence-based medicine is not about speculations but about what the effect is on average. It is sobering to be reminded that psychosis pills kill nerve cells so effectively that their possible use against brain tumours has been explored. 4:176,135
These authors noted that the brain shrinkage is related to the dose of psychosis pills but also that the sickest patients receive the largest doses (confounding by indication), and that it is therefore difficult to make a judgment. They added that more recent data had shown a relationship between relapse and progressive shrinkage, which suggested that the psychosis can be toxic.
There were no literature references, but the relationship between relapse and shrinkage does not suggest that psychosis can be toxic. Using their own argument, that a harmful effect of the drugs cannot be excluded, the shrinkage might as well be caused by the drugs.
Another textbook noted that that animal experiments have shown that psychosis drugs reduce grey matter,17:314 with a reference.235 It added that this has partly been confirmed in human studies, but that the literature is equivocal. One of the authors was Merete Nordentoft, a leading schizophrenia researcher. It is strange that she did not mention Nancy Andreasen’s well-known studies.63,64 Despite the huge potential for bias in brain imaging studies (see Chapter 3), such studies and meta-analyses of them—performed by people who, judging from their papers, clearly didn’t like what they found—have convincingly shown that psychosis pills shrink the brain.63,236 They do this in a dose-dependent manner1,63 and they also shrink the brain in primates, which do not suffer from psychosis.235 In contrast, the severity of illness has minimal or no effect.63
There is no reliable evidence that a psychosis per se can damage the brain,237 and although a large study claimed this,64 it couldn’t separate the effects of treatment from any possible effect of the disease, which the authors acknowledged. A study that included patients with first-episode psychosis found that short exposure to psychosis pills could lead to brain shrinkage of grey matter, again with no relation to the severity of the illness.238
Imaging studies can always be discussed but if we turn to the extrapyramidal harms of psychosis pills, there is no doubt that they cause permanent brain damage. These harms consist of various involuntary movements, which include akathisia; dystonia (painful muscle spasms); Parkinsonism (which include tremor, difficulty finishing thoughts or speaking, stiff facial muscles and difficulty walking); and tardive dyskinesia (facial movements including sucking or chewing motions of the mouth, sticking out the tongue, blinking the eyes a lot, and inability to sit or lie still, with constant movements of the extremities).11 Patients with tardive dyskinesia have higher mortality rates, and this harm is dose-related.1
One textbook noted that tardive dyskinesia is often reversible.19:286 This is wrong7,135 and was contradicted by another book that spoke about irreversible movement disorders.17:314
Among the harms of psychosis pills, the textbooks mentioned dystonia, dyskinesia, akathisia, Parkinsonism, malignant neuroleptic syndrome, sexual dysfunction, erectile dysfunction, retrograde ejaculation, decreased libido, cardiometabolic harms, influence on heart rhythm, QT prolongation, torsade de pointes, deadly ventricular tachycardia, orthostatic hypotension, sinus tachycardia, metabolic syndrome, type 2 diabetes, stimulation of the appetite centre with weight increase, prolactin increase, galactorrhoea, gynaecomastia, amenorrhea, osteoporosis, possibly breast cancer, nasal stenosis, influence on memory and cognition, dry mouth, constipation, urine retention, and blurred vision. 16:563,18:235,19:236,19:278 A remarkable omission in most of the lists of harms in the textbooks was tardive dyskinesia.
The risk of developing malignant neuroleptic syndrome was largely ignored for many years, but it has been estimated that 100,000 Americans died from it in a 20-year period and that 80,000 might have lived if the physicians had been warned against it.1:208
One textbook warned against QTc prolongation but only if the patients receive other drugs with such effects.17:656 This advice is deadly. Some people have a long QTc interval naturally and they can suddenly die if they are treated with a psychosis drug as the only drug.
We are told that clozapine and olanzapine carry the highest risk of obesity, diabetes and cardiovascular disease,17:655 which makes it difficult to understand why these drugs are so popular. Another textbook mentioned that meta-analyses have shown that the biggest risk of metabolic harms is seen with clozapine and olanzapine, and that patients on olanzapine gain more in weight than those on other drugs.16:564
Only one textbook informed honestly about the serious harms.16:563 It noted that the extrapyramidal harms are dose-dependent, and that tardive dyskinesia is a severe harm, which may be irreversible and has an incidence of about 5% per year with first-generation drugs but is also seen with second-generation drugs. It mentioned that akathisia, in severe cases, can contribute to increased suicide risk and can be confused with psychomotor agitation as a result of the psychotic condition, leading to a dose increase, worsening the situation. Akathisia was said to occur in 25% of the patients on first-generation drugs and to a lesser degree with second-generation drugs.
Not even this book could refrain from semantically downplaying the problems. Akathisia does not contribute to increasing the suicide risk, it causes an increased risk. No other factors in the causal chain are needed for suicides to happen.7
Two books were dangerously dishonest.17:654,18:235 They claimed that first-generation drugs cause extrapyramidal harms, which can be irreversible in the case of tardive dyskinesia,17:655 and that these harms can be avoided by using second-generation drugs.17:657 As already noted, this marketing message is false; the newer drugs are not any better in this respect.239 Furthermore, when the authors stated that some patients with akathisia consider suicide, they did not say that this also applies to second-generation drugs. A third book that mentioned akathisia19:286 failed to note that it is a dangerous harm that increases the risk of suicide and violence.7
There are videos of children and adults with akathisia and tardive dyskinesia that show how horrible these brain damages can be.240 It took psychiatry 20 years to recognize tardive dyskinesia as an iatrogenic illness,7:163 even though it is one of the worst harms of psychosis pills and also one of the most common ones, affecting about 4-5% of the patients per year.241 In 1984, Poul Leber from the FDA extrapolated the data and concluded that, over a lifetime, all patients might develop tardive dyskinesia.11:368 Three years later, the president of the American Psychiatric Association said at an Oprah Winfrey show that tardive dyskinesia was not a serious or frequent problem.242
Neurologists are much better at spotting tardive dyskinesia than psychiatrists and the same applies to researchers. Among 58 consecutively admitted patients with acute psychosis, 48 of whom were treated for at least a week with psychosis drugs, the researchers found 10 patients with tardive dyskinesia, but the psychiatrists only made this diagnosis in one of them.243 The akathisia diagnosis is also often missed or misinterpreted, particularly when the symptoms involve the extremities rather than the face. In the same study, the researchers diagnosed akathisia in 27 patients, the clinicians only in 7.243 In a community sample of patients with schizophrenia, the prevalence was 19%.244
There are several reasons why akathisia might go undetected.245 Its symptoms resemble and often overlap with those of other psychiatric disorders, such as mania, psychosis, agitated depression, and ADHD. In addition, akathisia often occurs concurrently with, and is masked by, akinesia, a common extrapyramidal harm of psychosis pills. Such patients might have the inner feeling of restlessness and urge to move but do not exhibit characteristic limb movements but sit still, in a state of inner turmoil. When akathisia is mistaken for worsening anxiety, psychosis, or agitated depression, the clinician usually increases the dosage of the offending agent, leading to further harm.
Even less recognised than akathisia is tardive akathisia,11:70 which has a delayed onset, usually more than three months since a medication or dose change. It is often associated with tardive dyskinesia. A journalist described his experience this way: “And then, one day about four months after my taper [of a depression pill], I woke up shaking, with a sense of impending doom like nothing I’d ever experienced.”246
Akinesia is frequently overlooked or misdiagnosed as depression. Akinesia should therefore be considered in the differential diagnosis of any patient taking psychosis pills that becomes amotivational, depressed, lethargic, or slowed down. Severe forms of akinesia tend to be overlooked more often than mild cases, which might be because severely affected patients complain less about their symptoms.
What was totally missing in the textbooks were the harms psychiatrists inflict on their patients that are not drug harms. There was nothing about the lack of hope that occurs when psychiatrists stigmatise their patients by telling them they have schizophrenia and say it is a lifelong disease that sometimes requires lifelong treatment with psychosis pills, and subject them to forced treatment with these drugs.
Understandably, this increases the risk of suicide considerably.7 A 2014 Danish register study of 2,429 suicides showed that the closer the contact with psychiatric staff—which often involves forced treatment—the worse the outcome.247 Compared to people who had not received any psychiatric treatment in the preceding year, the adjusted rate ratio for suicide was 6 for people receiving only psychiatric medication, 8 for people with psychiatric outpatient contact, 28 for people with psychiatric emergency room contacts, and 44 for people who had been admitted to a psychiatric hospital. Patients admitted to hospital would of course be expected to be at greatest risk of suicide because they are more ill than others (confounding by indication), but the findings were robust and most of the potential biases in the study were conservative, i.e. favoured the null hypothesis of there being no relationship.
An accompanying editorial noted that there is little doubt that suicide is related to both stigma and trauma and that it is entirely plausible that the stigma and trauma inherent in psychiatric treatment—particularly if involuntary—might cause suicide.248 The editorialists believed that some people who commit suicide during or after an admission to hospital do so because of conditions inherent in the hospitalisation.
One textbook mentioned 10 risk factors for suicide,18:131 but admission to a psychiatric ward was not among them even though this seems to be the greatest risk of all.
Lithium and antiepileptics
By and large, the information on lithium in the textbooks was incorrect (as I will explain further in Chapter 8). One book claimed that lithium has a prophylactic effect in schizoaffective disorders and can dampen aggression,18:241 with no reference. However, a systematic review of 22 trials of lithium for schizophrenia found no reliable evidence that lithium worked.249 The trials were generally small, with only 35 patients on average, of short duration, incompletely reported, and insufficiently blinded, and a positive effect disappeared when non-double-blind studies or those with high attrition were excluded. I updated the search in April 2022 by searching on lithium schizo* in the title field on PubMed and did not find any additional trials.
Psychotic patients are often treated with antiepileptics. As far as I can see, lithium and antiepileptics (see below, under bipolar disorder) should not be used in patients with psychosis.
Benzodiazepines
One textbook mentioned that agitation increases the risk of suicide and aggressive behaviour towards staff and other patients, and that it may be due to intoxication with psychoactive substances, abstinences, or harms of psychiatric drugs.16:84
These authors recommended non-pharmacological interventions for acute agitated conditions, e.g. de-escalation techniques,16:85 and they said that psychosis drugs are better than benzodiazepines if drugs are needed. In the same book, another author said that benzodiazepines are important in an acute agitated phase of psychosis,16:577 and that the effect is equivalent with that of psychosis pills.16:560
The drug industry has of course shied away from comparing their highly expensive psychosis pills with off-patent benzodiazepines that can be acquired almost for free, and psychiatrists failed to live up to their professional responsibility by neglecting to perform such trials themselves.
In 1989, 35 years after chlorpromazine came on the market, only two trials had compared the two types of drugs, and they produced similar improvements.5:200
In 2012, there were 14 head-to-head trials, summarised in a Cochrane review.165 The desired sedation occurred significantly faster with a benzodiazepine than with a psychosis pill, but the authors paid tribute to the drug industry by providing a conclusion that did not agree with their results: “There is currently no convincing evidence to confirm or refute the practice of administering benzodiazepines as monotherapy.”
There surely was, and we should use benzodiazepines if sedation is needed in the acute phase. The psychiatrists who did the Cochrane review noted that the trials they reviewed were of poor quality, but it is the best evidence we have.
When I lecture for psychiatric patients, I often ask them which drug they would prefer next time they became admitted acutely and needed something to calm them down. All of them have preferred a benzodiazepine. It is therefore unethical to force them to take a psychosis pill or to give them an involuntary injection with a psychosis drug, but this is standard practice.
Since acute psychosis tends to disappear again if left untreated, psychiatrists should be very reluctant to use drugs, apart from a benzodiazepine for a few days.
An Icelandic psychiatrist told me that when he worked at a psychosis ward in London, he and his colleagues waited on average about two weeks before starting psychosis medication on newly admitted people. Most people chose to take some medication, but often in very small doses, so it is very well possible that it was respect, time, and shelter that helped the patients, not the “sub-treatment threshold doses.”
Psychiatrist Simon Wilkinson from Akershus University Hospital in Norway told me that they don’t have a regime for rapid tranquillisation and have never needed one.
It is all a question of the prevailing culture. Psychiatrists could do vastly better by meeting the patients where they are while mustering all the respect and empathy they can, without forced drugging.
Psychotherapy and caring
As noted above, psychotherapy was generally not a stand-alone treatment option but a supplement to pills.
This is a serious blunder. The authors of the Cochrane review, which pointed out that we don’t have evidence that psychosis drugs in an acute early episode of schizophrenia is effective,154 included a randomised trial by Loren Mosher in their review.250 Mosher compared 55 patients in hospital, all of whom received psychosis drugs, with 45 patients treated in a non-hospital milieu where 67% did not receive psychosis drugs, and the results after six weeks were virtually the same.
Mosher wasn’t against using psychosis drugs.7:168 He opened a 12-room Soteria house in 1971, as he wanted to treat acutely psychotic people in a humanistic way with empathy and caring. There were no locks on the doors, and the idea was to treat people with respect.
His staff were not mental health professionals but people who had social skills and empathy and who listened to the patients’ stories, which often revealed traumas with abuse and extreme social failure.251 Thus, Mosher paved the way for the Open Dialogue approach (see Chapter 7, Part Three).
The good results obtained by Mosher, also after the randomised trial, by avoiding using psychosis drugs were too threatening to other psychiatrists.1 His patients had fewer relapses and functioned better in society in terms of holding a job and attending school than those on drugs. It was offensive to the psychiatrists to suggest that ordinary people could help crazy people more than psychiatrists with their drugs. But Mosher was the chief of the Center for Studies of Schizophrenia at the US National Institute of Mental Health, so it wasn’t obvious how he could be stopped.
The NIMH clinical project committee raised doubts about the scientific rigour of his research team and reduced the funding for Mosher’s project to such a low level that it was a financial kiss of death.1 This is the standard method used in healthcare by those who hold the power when the results of a project threaten the status quo and their carefully pruned self-image. Mosher tried to get around the obstacle by applying for funding from the NIMH division that dealt with social services, and the peer review committee was very enthusiastic. However, the clinical projects committee killed his project right off, as it threatened the very credibility of academic psychiatry with its medical model of drug therapy. This was done with derogatory remarks about the study’s postulated “serious flaws” and with the fatal blow that further funding would only come forward if Mosher stepped down so that the committee could redesign the project with another investigator.
This is one of the ugliest manoeuvres I have ever seen being used against a high-ranked investigator who was a treasure for the patients, and a bitter Mosher said 25 year later: “If we were getting outcomes this good, then I must not be an honest scientist.”1:224 The NIMH made Mosher an outcast and threw him out of the NIMH three years later. Others in America who questioned the merits of psychosis pills learned quickly that this would not advance their career, and NIMH did not allot any more funds to this type of project.5 Many years later, the first author on the Cochrane review analysed the follow-up data from Mosher’s study and discovered that they were even more positive than what Mosher had published.1:225
Psychotherapy for schizophrenia seems to be cost-effective. According to a NICE guideline from 2012, a systematic review of the economic evidence showed that cognitive behavioural therapy improved clinical outcomes at no additional cost, and economic modelling suggested that it might result in cost savings because of fewer hospital admissions.252
It wasn’t until 2014 that the first trial of psychotherapy in people with schizophrenia who were not on drugs was published.253 All the patients had declined to be treated with drugs. The effect size was 0.46 compared to treatment as usual, about the same as that seen in seriously flawed trials comparing psychosis pills with placebo, which is a median of 0.44.254
This means that the effect of psychotherapy is likely better than the effect of pills.
US Psychiatrist Peter Breggin has described what a remarkable effect empathy, caring and understanding can have in patients with severe schizophrenia.135 As an 18-year old college freshman without mental health training, he volunteered at a state mental hospital and approached the patients as he would want himself to be approached, with care and concern, and with a desire to get to know the patients and finding out what they needed and wanted.
He was immediately appalled by how abused and humiliated the patients were by the authoritarian and sometimes violent staff, and by the brain-damaging treatments they used, including insulin coma therapy, electroshock, and lobotomy, all the while he was told that these treatments “killed bad brain cells,” which he found unlikely to be true of course.
Breggin developed an aide programme in which 15 students were assigned their own patient among those who were chronic inmates considered beyond help—burnt out schizophrenics—who had not yet been subdued by chlorpromazine. They were able to help 11 of the 15 patients to return home or to find improved placements in the community. During the next one to two years only three patients returned to the hospital.
Breggin’s programme drew national headlines and was praised as an important innovation by the Joint Commission on Mental Illness and Health in 1961. This was the last psychosocially oriented document to be issued by the NIMH. Ever since, the focus has been on co-operative efforts with the drug industry to promote biochemical explanations and drugs.
Psychiatrists have found out recently that if they talk more with their patients with schizophrenia, there is less need of forced treatment. Merete Nordentoft conveyed this positive experience in a TV debate with me. I wondered why this was something psychiatrists should discover. Shouldn’t they have known this all along?
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To see the list of all references cited, click here.
Reading chapter 7 on psychosis for me was very interesting. I do believe psychopharmacology plays a significant role in treating psychosis but the high reliance on drugs have created a lest than holistic care of persons with brain illnesses. It would appear that most psychiatrist has related themselves to prescribers rather than therapist.
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Using drugs you can “treat” more patients. More important, you can generate more fees.
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The drug companies & medical establishment lose a lifelong cash cow if a patient is cured.
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Scares me.
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