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 lack of evidence for benefit, and the evidence of harms, of psychosis drugs used for early intervention/first-episode psychosis. Each Monday, a new section of the book is published, and all chapters are archived here.
Early intervention? Yes, but not with psychosis drugs
An argument for using psychosis drugs was that it is harmful not to intervene early, and the term “duration of untreated psychosis” (DUP) was often used. It was claimed that DUP worsens the prognosis for schizophrenia and similar disorders;16:194,17:326,18:79,18:233 19:235,20:416 that it is harmful for the brain to be psychotic;18:98,20:416 and that with early intervention, a chronic course can be prevented for many patients17:326 who can be taught to handle their vulnerability.18:80
These arguments are not correct. When a drug doesn’t work for a disease but only pacifies the patients, it cannot be important to use it early in the course of a disease. Furthermore, the research—none of which was referenced—that claims that the duration of untreated psychosis is related to the prognosis is unreliable. People who are not treated early are not comparable to those treated early and they are in a worse condition, on average, with a host of prognostic factors that bode for a poor long-term outcome, e.g. homelessness and alcoholism.
It is not possible with statistical methods to adjust reliably for such differences. As already noted, the more variables you include in a logistic regression, the further you are likely to get from the truth50 (see Chapter 2, Part Two).
One textbook noted that acute psychosis can be preceded by acute stress or trauma, and that full remission will usually be seen within a few months, often in a few weeks or even days.16:232 This makes it even more unacceptable that the authors a few pages later recommended second generation psychosis pills and even said that “mood stabilisers”—likely antiepileptics—can be used, in addition.
Psychiatrists also claimed that psychosis drugs are often a prerequisite for psychotherapy and that drug-free treatment has been tried for acute psychosis in some countries, but can be very dangerous, with a likely risk of brain damage and a high risk of suicide.18:233
If patients are very agitated, it may help getting in contact to sedate them, but benzodiazepines are better at this than psychosis pills.165 And it is usually easier to practice psychotherapy on a patient who is not sedated than on one who has difficulty concentrating and focusing.
It is outrageous to suggest that it can be very dangerous not to use psychosis pills. It is very dangerous to use them; they do not protect against brain damage but cause irreversible brain damage;63,64 and they do not lower the risk of suicide, they likely increase it because of withdrawal effects, e.g. when the patients need a drug holiday, which increases the risk of akathisia,134 and thereby of suicide and violence.7
Patient reports on the internet show that suicidal thoughts when taking psychosis pills are strongly associated with akathisia; 13.8% of respondents reporting akathisia also reported suicidal thoughts, compared with 1.5% of those who didn’t mention akathisia (P < 0.001).160 This harm would be expected to be related to the dose of the previous drug, which it clearly is.170
Akathisia was given little attention for many years, and physicians generally interpreted restless behaviour as a sign that patients needed a higher dose of the drug, which aggravates the situation. When the psychiatrists finally took an interest in this, the results were shocking. In one study, 79% of mentally ill patients who had tried to kill themselves suffered from akathisia.1:187 A 1990 study reported that half of all fights at a psychiatric ward were related to akathisia,171,172 and another study found that moderate to high doses of haloperidol made half the patients markedly more aggressive, sometimes to the point of wanting to kill their “torturers,” the psychiatrists. Psychotropic drugs can cause people to lose some of their conscience, losing control over their behaviour.21 Such people are at greatly increased risk of committing acts of crime and violence.
A textbook claimed that clozapine seems to be able to reduce suicidal behaviour in patients with schizophrenia, and it mentioned that two small studies suggest that classic psychosis pills can be preventative across diagnoses.17:811 This wishful thinking was cleverly manipulated by using the expression “seems to”; by referring to two small studies rather than telling us what all studies showed; and by omitting the two studies in the reference list after the chapter, leaving the reader in total darkness. This was the antithesis of evidence-based medicine.
Early intervention in schizophrenia is beneficial, provided it is not with psychosis pills but with psychosocial interventions.7:170 In 1969, the WHO launched a study that showed that patients fared much better in poor countries—India, Nigeria, and Colombia—than in the United States and four other developed countries.1:226 At five years, about 64% of the patients in the poor countries were asymptomatic and functioning well compared to only 18% in the rich countries.
Western psychiatrists dismissed the results with the argument that patients in poor countries might have milder disease. WHO therefore did another study, focusing on first-episode schizophrenia diagnosed with the same criteria in 10 countries.1:228 The results were pretty similar: about two-thirds were okay after two years in the poor countries versus only one-third in the rich countries.
The WHO investigators tried to explain this big difference with various psychosocial and cultural factors, but didn’t succeed. The most obvious explanation, drug use, was so threatening to Western medicine that it went unexplored. People in poor countries couldn’t afford psychosis pills, so only 16% of the patients were regularly maintained on them, compared with 61% in rich countries.
A more recent study performed by Eli Lilly failed to find differences between poor and rich countries, but in this study all patients were treated with drugs, half of them with Lilly’s drug, olanzapine, the other half with other psychosis pills.173
A 20-year study from Chicago by Martin Harrow showed that, among 70 patients with schizophrenia, those who were not on psychosis drugs after the first two years had far better outcomes than those who were on drugs.174 This was not due to confounding by indication. The adjusted odds ratio of not being on drugs was 5.99 (3.59 to 9.99) for recovery and 0.13 (0.07 to 0.26) for rehospitalization.
Harrow was a prominent schizophrenia researcher at the National Institute of Mental Health, and other researchers arrived at similar results, but they all experienced that their funding dried out.1,5
Apart from avoiding the harmful effects of psychosis pills, there are other reasons why people with schizophrenia fared so well in poor countries.175 The illness is often seen as the result of external forces, e.g. evil spirits, and people are much more likely to keep the sufferer in the family and to show kindness, which helps patients recover and participate in social life again.
Few psychiatrists know about this. Some have asked me whether it would be more humane than using drugs to deprive people of their liberty by tying them to a tree. This may happen in Africa, but overall, the communities did a far better job in Africa than we do in the Western world where we have institutionalised deprivation of liberty through legal means and forced treatment and have killed hundreds of thousands of patients with psychosis pills.6:232 This is not a humane system.
The famous Open Dialogue Family and Network Approach initiative in Lapland aims at treating psychotic patients in their homes.8:91 The treatment involves the patient’s social network and starts within 24 hours after contact.176
A comparison between Lapland and Stockholm illustrates the difference between an empathic approach and immediately forcing drugs on patients with a first-episode psychosis.176,177 The patients in Lapland were closely comparable to those in Stockholm, but in Stockholm, 93% were treated with psychosis pills against only 33% in Lapland, and five years later, ongoing use was 75% versus 17%. After five years, 62% in Stockholm versus 19% in Lapland were on disability allowance or sick leave, and the use of hospital beds had also been much higher in Stockholm, 110 versus only 31 days, on average. It was not a randomised comparison, but the results are so strikingly different that it would be irresponsible to dismiss them. Furthermore, there are many other results supporting a non-drug approach to acute psychosis.7:330
The Open Dialogue model is gaining momentum in several countries, and randomised trials are ongoing. It started 25 years ago,176 and it was therefore surprising that the textbooks didn’t mention it. Denmark has its own version of early intervention along similar principles, which started at about the same time. It is called OPUS because an orchestra consists of many different instruments, all working together to play a piece of music. The idea with OPUS is to create a partnership between the patient and all those who are part of the treatment, including the family and social network.
The textbooks acknowledged that psychosocial interventions have a role in the treatment of schizophrenia,16:615,20:418 and there were many remarks about the positive effects of these initiatives, e.g. of family involvement, outreach,16:194,17:313 assertive community treatment on patient terms,16:616,17:313 multidisciplinary teams, cognitive behavioural therapy,16:224,17:318 and neuro-cognitive training.16:624
It was noted that the OPUS study in Denmark and the AESOP study in England showed that more than half of the patients no longer had psychotic symptoms after 10 years.16:205 Studies have shown a reduction in readmissions, fewer hospital days, and an effect on psychotic symptoms, drug abuse, and negative symptoms.16:617
One book claimed, without references, that studies have shown that cognitive behavioural therapy can alleviate both psychotic and negative symptoms, and that randomised trials have shown that family intervention halves the risk of relapse and hospital days.17:318 Another book referred to a systematic review,16:620 which found that family psychosocial interventions halved the frequency of relapse of schizophrenia or schizoaffective disorder.178 Hospital admissions were reduced by 32% whereas hospital days were only available in two small Chinese studies.
The authors noted that the treatment effects might be overestimated due to poor quality of the trials, e.g. insufficient blinding of the assessors. However, the effect on relapse was so large that it could hardly be caused by bias alone.
One book noted that supported employment made it three times more likely that the patients would find work.16:625 The reference was to a Cochrane review of trials in severe mental illness and by far most of the patients were diagnosed with schizophrenia or schizoaffective disorder. The review noted that the evidence was of very low quality.179 This was mainly because none of the 14 studies were blinded: “Participants could identify the given intervention by contents of the program.”
Of course they could. Some interventions just cannot be blinded, but conclusions like these are produced when researchers slavishly follow the Cochrane cookbook approach, which down-grades the quality of the evidence for many useful interventions that cannot be blinded like a drug trial can.
It is unfortunate that Cochrane reviews routinely downgrade the results of psychosocial interventions, as they are so clearly superior to drugs. Another issue was that days in competitive employment, the review’s primary outcome, was only reported in half of the 14 studies, which is more serious, as all the studies were about supported employment.
One of the books, which only had psychiatrists as authors, was even more focused on drugs than Cochrane reviews are. It claimed that environmental therapy and psychotherapeutic techniques can be used when the acute psychosis is under control with psychosis pills.18:79 This is wrong. Psychotherapy can abolish the need for psychosis pills in many cases, as demonstrated by the experience with the Open Dialogue model and other approaches such as OPUS.
This book also contradicted itself. It noted that psychotherapy is recommended only in the stabilisation phase,18:99 but on the next page, it said—when commenting on OPUS—that psychotherapy can also be used from the very beginning. Curiously, still on this page, the book claimed erroneously that psychosis pills are often a prerequisite for improvement and for making it possible to include the patient in other offers.18:100
The book also claimed that cognitive behavioural therapy is the only form of therapy for which there is evidence for an effect in psychosis.18:102 This is also wrong. Family intervention, psychoeducation, and mindfulness are also effective.180
Finally, the book noted that psychotherapy was not recommended for acute mania but was a well-documented supplement to medication as prevention.18:117 We got it by now. Give them all drugs. Everything else is supplementary, if used at all. Even this recommendation was dubious. A network meta-analysis showed that psychoeducation plus cognitive behavioural therapy has a large effect on manic symptoms compared with treatment as usual, effect size −0.95 (−1.47 to −0.43).181
A much more reasonable book, which is the one that wrote the most about OPUS,16 offered five references to Cochrane reviews in a literature list that was not directly linked to the statements about its effects. I have commented on two of them just above.178,179 The other three were not particularly convincing.
One review was about intensive case management of severely mentally ill people in the community that included 40 trials, but most of them had a high risk of selective reporting of the outcomes, and not a single one provided data for relapse or important improvement in mental state.182 Despite this, the authors wrote 273 pages for their Cochrane review—the size of a book—and concluded that the intervention is effective in ameliorating many outcomes and may reduce hospitalisation, increase retention in care, and globally improved social functioning. Lovely, but difficult to know if this is just wishful thinking given how poor the evidence was.
The second Cochrane review was about shared decision-making, but there were only two studies. The authors wrote 45 pages about them even if they could not conclude anything.183 But we need not study shared decision-making in randomised trials. We have an ethical obligation to respect the patients and involve them in our decisions. This ethical imperative cannot be suspended, not even when the patients are psychotic, according to the United Nations Convention on the Rights of Persons with Disabilities, which has been ratified by virtually all countries except the United States.7:333,184 In 2014, the Convention specified that member states must immediately begin taking steps towards the realisation of the rights by developing laws and policies to replace regimes of substitute decision-making by supported decision-making, which respects the person’s autonomy, will, and preferences.184
The third Cochrane review was about early intervention for psychosis.185 Even though there were 18 studies, they were diverse, mostly small, undertaken by pioneering researchers, and had many methodological limitations, which generally made meta-analyses inappropriate. The authors found the evidence inconclusive but nonetheless wrote 134 pages about it. It is interesting that they did not find convincing evidence for early intervention with drugs, as this was touted as being important in several textbooks (see above).
One textbook noted that psychosis pills dampen or remove positive symptoms such as hallucinations, delusions, thought disturbances, and catatonia.18:86,18:234 This gives the erroneous impression that the drugs are highly effective and have specific effects on psychosis. They work in the same way on patients, healthy volunteers, and animals;7 they are major tranquillisers, which was what they were called in the distant past; and they cannot remove hallucinations or delusions. When chlorpromazine came on the market in 1954, it was first considered a chemical lobotomy, as it produced many of the same effects as lobotomy. It was also called a chemical straitjacket, as it kept the patients under control, and the psychiatrists noted that it didn’t have any specific anti-psychotic properties.1-142
It was recommended to treat pregnant women with schizophrenia because untreated psychosis can endanger the life of the mother and child.17:669 There was no thoughts about that the pills just increase this risk further. This book noted that the US FDA in 2011 issued a general warning against using psychosis drugs because of extrapyramidal symptoms and withdrawal symptoms, which suggest that the drugs affect the brain in both the child and the mother.
Suggest that the drugs affect the brain? We have known for 70 years that the drugs hamper normal brain functions,1:142 which is why they are being used. How can people supposed to be experts in psychopharmacology, which was the title of their chapter, write such nonsense? Well, they were all professors of psychiatry, which seems to be a carte blanche for people to write whatever they please.
In the package inserts for psychosis pills, e.g. for olanzapine,134 the FDA warns that the drugs should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. This is not helpful advice. How should a doctor make such a judgment? FDA notes that neonates exposed to psychosis pills during the third trimester are at risk for extrapyramidal and withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in neonates, and in some cases, this has required intensive care unit support and prolonged hospitalisation. But according to Danish professors of psychiatry, it is only a possibility that psychosis pills affect the brain.
One book noted that patients with a diagnosis of schizotypy, which is a very dubious concept (as I will explain in Chapter 15),8:145 should be treated with psychosis pills if there are thought disorders, ruminations, or psychotic episodes, as 25% develop schizophrenia.18:106 There is no evidence for this, and many people have thought disturbances from time to time or ruminate.
In essence, this is a plea for prophylactic treatment of reasonably healthy people with toxic drugs, a horrible idea. The diagnostic test for this disorder is useless and bogus,8:145 and it seems that most psychiatrists would test positive (as I will explain in Chapter 15). Most psychiatrists should therefore be in prophylactic treatment with psychosis pills, according to the advice in this textbook.18:106
Four books claimed that the pills work also for negative symptoms.16:206,17:653,18:81,20:416 Negative symptoms include blunted affect, alogia (poverty of speech), asociality, avolition (lack of motivation or ability to do tasks or activities that have an end goal), and anhedonia (diminished capacity to experience pleasant emotions).186 It was also claimed, in two textbooks, that psychosis pills have an effect on cognitive symptoms, 17:653,20:416 but two pages further ahead one of them noted that cognitive disturbances are largely unaffected.20:418
This information was confusing, contradictory, and wrong. The pills worsen negative symptoms and cognition, which has been known for 70 years,1:142,5,7 and which was acknowledged in one of the books.16:562
One book mentioned that psychosis drugs can inhibit sensory inputs and psychological functions, which can increase negative symptoms and social isolation.18:235 This directly contradicted claims in the same book, 154 pages earlier,18:81 that psychosis pills have an effect on negative symptoms.
This textbook also noted that psychosis drugs can lead to drug abuse to stimulate the brain’s reward system, which will worsen psychotic symptoms. It mentioned that direct sadness or depression occurs, but that it is often difficult to distinguish between a drug-induced depression from the understandable psychological reaction to having to live with a very severe disease, which has shaken one’s self-perception.18:235 This is the only time I came across an honest account of what psychosis pills really do to patients, and this is not beneficial for them.
One textbook claimed that several meta-analyses have shown that depression pills have an effect on negative symptoms.18:101 There wasn’t any reference to this remarkable statement. As I doubted it was correct, I looked up a couple of meta-analyses, which were both negative. One noted that “the quality of information is currently too limited to come to any firm conclusions;”187 the other that “the literature was of poor quality” and that the results could “merely reflect selective reporting of statistically significant results and publication bias.”188
This textbook noted that it can be difficult to distinguish between depressive symptoms, negative symptoms in psychosis, and harms of psychosis pills.18:101 Thus, two books admitted that psychosis pills worsen negative symptoms. Nonetheless, one book advised that, in case of persistent negative symptoms, some relief can be obtained by adding depression pills to the psychosis pills.16:577
This is a common theme in the textbooks. Instead of withdrawing the drug slowly that causes the problem, psychiatrists add additional drugs, which is an important reason for the massive overmedication of psychiatric patients that is well documented.5,7,8,113,114
No matter which psychiatric drugs people take—psychosis pills, depression pills, lithium, stimulants or benzodiazepines—or what their problem is, roughly one-third of the patients have their prescriptions renewed every year and are still in treatment with the same drug or a similar one 10 years later. 113,114
This tells a story of irresponsible doctors who don’t know what they are doing or what they are causing. It also confirms what I wrote in a newspaper article in 2014 that our citizens would be far better off if we removed all psychotropic drugs from the market, because it is clear that the doctors cannot handle them.189
Danish psychiatrists have admitted they have a problem. In a 2007 survey, 51% of 108 Danish psychiatrists said that they used too much medicine and only 4% that they used too little.190 But usage of psychiatric drugs has continued to increase markedly in most countries, e.g. in the UK, psychosis pill prescriptions increased by 5% per year on average and depression pills by 10%, from 1998 to 2010.191 We have not become more mentally ill to this degree. It is the effect of marketing and corruption.6-8
Psychiatry’s main focus for the next decades should be on helping patients withdraw slowly and safely from the drugs they are on, instead of telling them that they need to stay on them and adding even more.
But this won’t happen. Psychiatry’s focus is on itself—a kind of eternal selfie it sends to the world all the time.
To see the list of all references cited, click here.
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