Book Review: The Drugs Don’t Work? Antipsychotics, Big Pharma, and Psychiatry

Seena Fazel from the Department of Psychiatry, University of Oxford, UK reviews The Bitterest Pills: The Troubling Story of Antipsychotic Drugs by Joanna Moncrieff.

The first antipsychotic drugs were introduced to treat psychiatric patients in the 1950s, and since that time, they have become the principal pharmacological treatment for a wide range of severe psychiatric illnesses. These include schizophrenia, and bipolar disorder, which together effect 1.5-2% of the general population. They are also prescribed for other psychiatric conditions, particularly severe depression and anxiety, and personality disorders, where they are thought to relieve distressing symptoms. Prescription rates for antipsychotic drugs have increased over the last few decades, partly as the number of conditions for which they can be used has been widened. This increase has coincided with the introduction of a second generation of antipsychotics during the 1990s, which were reported to have less neuromuscular side effects. Spending on the antipsychotics has reached almost $17 billion in the US, and in the UK, it is estimated that the cost to the NHS is £282 million, overtaking antidepressants in 2007. Their increasing use has not been without its problems, particularly in individuals with behavioural problems. For example, in older people with dementia, research has demonstrated that they worsen cognitive impairment and this has led to their less frequent use in this population. Their use in children with challenging behaviours is controversial as the evidence for their efficacy is weak. In addition, antipsychotics are occasionally abused by adults as a ‘downer’, and there is an illegal market in prisons and elsewhere.

In The Bitterest Pills: The Troubling Story of Antipsychotic Drugs, Joanna Moncrieff, a psychiatrist and senior lecturer at University College London, provides an account of both the history and use of antipsychotic drugs. The book puts the case for the prosecution, which is both its strength and weakness. Moncrieff presents a survey of the history of these medications drawing on academic research, investigative journalism, and first-hand accounts to present a strong narrative that the evidence for the effectiveness of antipsychotics has been overstated, that they have been overprescribed for too long, and that many psychiatrists have been complicit in this abuse. Moncrieff’s use of drug company advertising materials over the last 50 years was particularly interesting, and remarkable as much for how it demonstrates how public attitudes towards mental illness have become less stigmatizing. The description of the discovery of many common antipsychotics and the alternatives that they replaced are useful reminders that the history of medicine has many examples of widespread practices with little evidence in support (such as insulin-coma therapy in psychiatry) and the chance discovery of many treatments, including chlorpromazine (originally used as an antihistamine) and haloperidol (found by a research team developing synthetic opiates). This historical narrative is interesting and engaging.

However, Moncrieff is writing as an advocate. Despite drawing on the scientific literature and the neutrality with which she writes most of the book, she occasionally lapses into positions that are quite eccentric. On the penultimate page, she states that the current model of understanding antipsychotic action (‘the disease-centered model’ in which antipsychotics act to correct the underlying dopamine dysfunction) ‘has played a major part in the obfuscation of the social control function that has always been embedded at the heart of psychiatry’ (page 219). Elsewhere, Moncrieff writes that the view that antipsychotics act by correcting an underlying disease ‘kept the genie of social control firmly inside the psychiatric lantern…. [and] made the practice of forced drugging respectable’ (page 143). This is an extreme view. Clearly, psychiatry has occasionally been abused but psychiatrists have also been instrumental in challenging such abuses. To suggest that ‘social control’ has ‘always’ been at its ‘heart’ would be a surprise to most psychiatrists who one would reasonably think are mostly motivated by treating illness and reducing distress. Other examples of unusual statements include that the dopamine hypothesis of schizophrenia is ‘pseudoscience’ (p. 74), and that the medications are ‘evil’ (p. 169).

Moncrieff presents in some detail a review of the trial data that informs the consensus view of almost all experts internationally that antipsychotics significantly reduce psychotic symptoms, rates of relapse and rehospitalisation, and other adverse outcomes in individuals with schizophrenia and related illnesses. Moncrieff’s view is that these data are subject to a range of biases, and the consensus view is incorrect. Clinical guidelines around the world have also come to very similar conclusions about the value of treating persons with schizophrenia with antipsychotics, and it is very difficult to believe that the experts sitting on these guideline committees, such as NICE in England, have all been duped by the ‘hopelessly flawed’ industry-sponsored research, and the marketing campaigns that accompany them.

One of the main criticisms that Moncrieff makes towards the trial evidence is it is primarily explained by the supersensitivity psychosis, that people who take antipsychotics suffer withdrawal psychotic symptoms when their medication is stopped. Thus randomised controlled trials that compare medication with placebo will invariably find that medication works as the individuals allocated to the placebo arms of these trials will be suffering from a withdrawal psychosis after stopping their antipsychotics. Supersensitivity psychosis may explain why the effects of antipsychotics slightly wear off over time, but the most recent and largest meta-analysis of antipsychotic trials, published in The Lancet last year by Stefan Leucht and colleagues, found no difference in risk of relapse at 7-12 months when the withdrawal was abrupt or tapered, or if the trial solely included patients with first episode psychosis compared with those who had several previous episodes. Another important finding that argues against Moncrieff’s view is that even if participants who had not relapsed for 9 months were included in these trials, antipsychotics were more effective than placebo. This is indicative of a problem with the book more generally. As Moncrieff does not intend The Bitterest Pill to be a systematic and transparent presentation of the research literature, and nor should it be, most readers will not be able to evaluate how selective Moncrieff has been in her presentation of the evidence. What is presented is quite depressing to read and suggests that antipsychotics should only be used for short periods of time in severely ill people. The problem with this extreme position is that the alternatives offered (such as using benzodiazepines) have even less evidence in support, and are subject to the same biases that Moncrieff highlights with industry-sponsored antipsychotic drug trials. It may also persuade patients and carers who have benefited from maintenance treatment to discontinue their medication.

The Bitterest Pill presents an opening argument against antipsychotics. It is useful insofar as it highlights the experience of patients taking these medications, the difficult history of many psychiatric treatments, and the overdiagnosis and overtreatment that seems to be prevalent in much of medicine including psychiatry. It carefully but selectively reviews the research evidence, and highlights the considerable problems with antipsychotics. However, a more judicious and cautious approach to the evidence would be more helpful for patients, carers, and their doctors, rather than extreme positions on either side. Having read the book, I came away thinking even more of the need for continual and critical reviews of the evidence base, the importance of non-industry funded research, and the relative ease with which the public face of psychiatry can be attacked. Books for the defence need to be written that focus on key problems for patients and public health – underfunded and overstretched psychiatric services in high income countries, and the continued scarcity of such services in low and middle income countries. Even in America, the three largest institutions that treat psychiatric patients are jails, many of whom according to recent surveys by the Department of Justice are subject to appallingly high rates of sexual abuse. Books like Moncrieff’s that only target the drugs and their manufacturers miss the mark.

The Bitterest Pills: The troubling Story of Antipsychotic Drugs by Joanna Moncrieff is published by Palgrave Macmillan, ISBN: 978-1-137-27743-5

Seena Fazel is a Wellcome Senior Research Fellow in Clinical Science at the department of Psychiatry, University of Oxford, UK.

Competing interests statement: I am researching the effects of antipsychotic medication on adverse outcomes in psychiatric patients. I have not worked as a consultant or advisor for a pharmaceutical company, nor received any research grants. Travel to three conferences during 2002-2004 was subsidized by a pharmaceutical company.