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The Emperor’s New Drugs makes an overwhelming case that what had seemed a cornerstone of psychiatric treatment is little more than a faulty consensus. But Kirsch does more than just criticize: he offers a path society can follow so that we stop popping pills and start proper treatment for depression.
For Leo, Alice, and the grandchildren yet to come
‘Brahms is the best antidepressant.’
The information in this book is not a substitute for professional advice on specific emotional issues. Please consult your GP before changing, stopping or starting any medical treatment, specifically antidepressant medication. So far as the author is aware the information given is correct and up to date as at 3 September 2009. The author and publishers disclaim, as far as the law allows, any liability arising directly or indirectly from the use, or misuse, of the information contained in this book.
Like most people, I used to think that antidepressants worked. As a clinical psychologist, I referred depressed psychotherapy clients to psychiatric colleagues for the prescription of medication, believing that it might help. Sometimes the antidepressant seemed to work; sometimes it did not. When it did work, I assumed it was the active ingredient in the antidepressant that was helping my clients cope with their psychological condition.
According to drug companies, more than 80 per cent of depressed patients can be treated successfully by antidepressants. Claims like this made these medications one of the most widely prescribed class of prescription drugs in the world, with global sales that make it a $19-billion-a-year industry.1 Newspaper and magazine articles heralded antidepressants as miracle drugs that had changed the lives of millions of people. Depression, we were told, is an illness - a disease of the brain that can be cured by medication. I was not so sure that depression was really an illness, but I did believe that the drugs worked and that they could be a helpful adjunct to psychotherapy for very severely depressed clients. That is why I referred these clients to psychiatrists who could prescribe antidepressants that the clients could take while continuing in psychotherapy to work on the psychological issues that had made them depressed.
But was it really the drug they were taking that made my clients feel better? Perhaps I should have suspected that the improvement they reported might not have been a drug effect. People obtain considerable benefits from many medications, but they also can experience symptom improvement just by knowing they are being treated. This is called the placebo effect. As a researcher at the University of Connecticut, I had been studying placebo effects for many years. I was well aware of the power of belief to alleviate depression, and I understood that this was an important part of any treatment, be it psychological or pharmacological. But I also believed that antidepressant drugs added something substantial over and beyond the placebo effect. As I wrote in my first book, ‘comparisons of anti-depressive medication with placebo pills indicate that the former has a greater effect . . . the existing data suggest a pharmacologically specific effect of imipramine on depression’. As a researcher, I trusted the data as it had been presented in the published literature. I believed that antidepressants like imipramine were highly effective drugs, and I referred to this as ‘the established superiority of imipramine over placebo treatment’.2
When I began the research that I describe in this book, I was not particularly interested in investigating the effects of antidepressants. But I was definitely interested in investigating placebo effects wherever I could find them, and it seemed to me that depression was a perfect place to look. Why did I expect to find a large placebo effect in the treatment of depression? If you ask depressed people to tell you what the most depressing thing in their lives is, many answer that it is their depression. Clinical depression is a debilitating condition. People with severe depression feel unbearably sad and anxious, at times to the point of considering suicide as a way to relieve the burden. They may be racked with feelings of worthlessness and guilt. Many suffer from insomnia, whereas others sleep too much and find it difficult to get out of bed in the morning. Some have difficulty concentrating and have lost interest in all of the activities that previously brought pleasure and meaning into their lives. Worst of all, they feel hopeless about ever recovering from this terrible state, and this sense of hopelessness may lead them to feel that life is not worth living. In short, depression is depressing. John Teasdale, a leading researcher on depression at Oxford and Cambridge universities, labelled this phenomenon ‘depression about depression’ and claimed that effective treatments for depression work - at least in part - by altering the sense of hopelessness that comes from being depressed about one’s own depression.3
Whereas hopelessness is a central feature of depression, hope lies at the core of the placebo effect. Placebos instil hope in patients by promising them relief from their distress. Genuine medical treatments also instil hope, and this is the placebo component of their effectiveness. When the promise of relief instils hope, it counters a fundamental attribute of depression. Indeed, it is difficult to imagine any treatment successfully treating depression without reducing the sense of hopelessness that depressed people feel. Conversely, any treatment that reduces hopelessness must also assuage depression. So a convincing placebo ought to relieve depression.
It was with that in mind that one of my postgraduate students, Guy Sapirstein, and I set out to investigate the placebo effect in depression - an investigation that I describe in the first chapter of this book, and that produced the first of a series of surprises that transformed my views about antidepressants and their role in the treatment of depression.4 In this book I invite you to share this journey in which I moved from acceptance to dissent, and finally to a thorough rejection of the conventional view of antidepressants.
The drug companies claimed - and still maintain - that the effectiveness of antidepressants has been proven in published clinical trials showing that the drugs are substantially better than placebos (dummy pills with no active ingredients at all). But the data that Sapirstein and I examined told a very different story. Although many depressed patients improve when given medication, so do many who are given a placebo, and the difference between the drug response and the placebo response is not all that great. What the published studies really indicate is that most of the improvement shown by depressed people when they take antidepressants is due to the placebo effect.
Our finding that most of the effects of antidepressants could be explained as a placebo effect was only the first of a number of surprises that changed my views about antidepressants. Following up on this research, I learned that the published clinical trials we had analysed were not the only studies assessing the effectiveness of antidepressants. I discovered that approximately 40 per cent of the clinical trials conducted had been withheld from publication by the drug companies that had sponsored them. By and large, these were studies that had failed to show a significant benefit from taking the actual drug. When we analysed all of the data - those that had been published and those that had been suppressed - my colleagues and I were led to the inescapable conclusion that antidepressants are little more than active placebos, drugs with very little specific therapeutic benefit, but with serious side effects. I describe these analyses - and the reaction to them - in Chapters 3 and 4.
How can this be? Before a new drug is put on the market, it is subjected to rigorous testing. The drug companies sponsor expensive clinical trials, in which some patients are given medication and others are given placebos. The drug is considered effective only if patients given the real drug improve significantly more than patients given the placebos. Reports of these trials are then sent out to medical journals, where they are subjected to rigorous peer review before they are published. They are also sent to regulatory agencies, like the Food and Drug Administration (FDA) in the US, the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK and the European Medicine Agency (EMEA) in the EU. These regulatory agencies carefully review the data on safety and effectiveness, before deciding whether to approve the drugs for marketing. So there must be substantial evidence backing the effectiveness of any medication that has reached the market.
And yet I remain convinced that antidepressant drugs are not effective treatments and that the idea of depression as a chemical imbalance in the brain is a myth. When I began to write this book, my claim was more modest. I believed that the clinical effectiveness of antidepressants had not been proven for most of the millions of patients to whom they are prescribed, but I also acknowledged that they might be beneficial to at least a subset of depressed patients. During the process of putting all of the data together, those that I had analysed over the years and newer data that have just recently seen the light of day, I realized that the situation was even worse than I thought. The belief that antidepressants can cure depression chemically is simply wrong.
In this book I will share with you the process by which I came to this conclusion and the scientific evidence on which it is based. This includes evidence that was known to the pharmaceutical companies and to regulatory agencies, but that was intentionally withheld from prescribing physicians, their patients and even from the National Institute for Health and Clinical Excellence (NICE) when it was drawing up treatment guidelines for the National Health Service (NHS) in the UK.
My colleagues and I obtained some of these hidden data by using the Freedom of Information Act in the US. We analysed the data and submitted the results for peer review to medical and psychological journals, where they were then published.5 Our analyses have become the focus of a national and international debate, in which many doctors have changed their prescribing habits and others have reacted with anger and incredulity. My intention in this book is to present the data in a plain and straightforward way, so that you will be able to decide for yourself whether my conclusions about antidepressants are justified.
The conventional view of depression is that it is caused by a chemical imbalance in the brain. The basis for this idea was the belief that antidepressant drugs were effective treatments. Our analyses showing that most - if not all - of the effects of these medications are really placebo effects challenges this widespread view of depression. In Chapter 4 I examine the chemical-imbalance theory. You may be surprised to learn that it is actually a rather controversial theory and that there is not much scientific evidence to support it. While writing this chapter I came to an even stronger conclusion. It is not just that there is not much supportive evidence; rather, there is a ton of data indicating that the chemical-imbalance theory is simply wrong.
The chemical effect of antidepressant drugs may be small or even non-existent, but these medications do produce a powerful placebo effect. In Chapters 5 and 6 I examine the placebo effect itself. I look at the myriad of effects that placebos have been shown to have and explore the theories of how these effects are produced. I explain how placebos are able to produce substantial relief from depression, almost as much as that produced by medication, and the implications that this has for the treatment of depression.
Finally, in Chapter 7, I describe some of the alternatives to medication for the treatment of depression and assess the evidence for their effectiveness. One of my aims is to provide essential scientifically grounded information for making informed choices between the various treatment options that are available.
Much of what I write in this book will seem controversial, but it is all thoroughly grounded on scientific evidence - evidence that I describe in detail in this book. Furthermore, as controversial as my conclusions seem, there has been a growing acceptance of them. NICE has acknowledged the failure of antidepressant treatment to provide clinically meaningful benefits to most depressed patients; the UK government has instituted plans for providing alternative treatments; and neuroscientists have noted the inability of the chemical-imbalance theory to explain depression.6 We seem to be on the cusp of a revolution in the way we understand and treat depression.
Learning the facts behind the myths about antidepressants has been, for me, a journey of discovery. It was a journey filled with shocks and surprises - surprises about how drugs are tested and how they are approved, what doctors are told and what is kept hidden from them, what regulatory agencies know and what they don’t want you to know, and the myth of depression as a brain disease. I would like to share that journey with you. Perhaps you will find it as surprising and shocking as I did. It is my hope that making this information public will foster changes in the way new drugs are tested and approved in the future, in the public availability of the data and in the treatment of depression.
Listening to Prozac, but Hearing Placebo
In 1995 Guy Sapirstein and I set out to assess the placebo effect in the treatment of depression. Instead of doing a brand-new study, we decided to pool the results of previous studies in which placebos had been used to treat depression and analyse them together. What we did is called a meta-analysis, and it is a common technique for making sense of the data when a large number of studies have been done to answer a particular question. It was once considered somewhat controversial, but meta-analyses are now common features in all of the leading medical journals. Indeed, it is hard to see how one could interpret the results of large numbers of studies without the aid of a meta-analysis.
In doing our meta-analysis, it was not enough to find studies in which depressed patients had been given placebos. We also needed to find studies in which depression had been tracked in patients who were not given any treatment at all. This was to make sure that any effect we found was really due to the administration of the placebo. To better understand the reason for this, imagine that you are investigating a new remedy for colds. If the patients are given the new medicine, they get better. If they are given placebos, they also get better. Seeing these data, you might be tempted to think that the improvement was a placebo effect. But people recover from colds even if you give them nothing at all. So when the patients in our imaginary study took a dummy pill and their colds got better, the improvement may have had nothing to do with the placebo effect. It might simply have been due to the passage of time and the fact that colds are shortlasting illnesses.
Spontaneous improvement is not limited to colds. It can also happen when people are depressed. Because people sometimes recover from bouts of depression with no treatment at all, seeing that a person has become less depressed after taking a placebo does not mean that the person has experienced a placebo effect. The improvement could have been due to any of a number of other factors. For example, people can get better because of positive changes in life circumstances, such as finding a job after a period of unemployment or meeting a new romantic partner. Improvement can also be facilitated by the loving support of friends and family. Sometimes a good friend can function as a surrogate therapist. In fact, a very influential book on psychotherapy bore the title Psychotherapy: The Purchase of Friendship.1 The author did not claim that psychotherapy was merely friendship, but the title does make the point that it can be very therapeutic to have a friend who is empathic and knows how to listen.
The point is that without comparing the effect of placebos against rates of spontaneous recovery, it is impossible to assess the placebo effect. Just as we have to control for the placebo effect to evaluate the effect of a drug, so too we have to control for the passage of time when assessing the placebo effect. The drug effect is the difference between what happens when people are given the active drug and what happens when they are given the placebo. Analogously, the placebo effect is the difference between what happens when people are given placebos and what happens when they are not treated at all.
It is rare for a study to focus on the placebo effect - or on the effect of the simple passage of time, for that matter. So where were we to find our placebo data and no-treatment data? We found our placebo data in clinical studies of antidepressants, and our no-treatment data in clinical studies of psychotherapy. It is common to have no-treatment or wait-list control groups in studies of the effects of psychotherapy. These groups consist of patients who are not given any treatment at all during the course of the study, although they may be placed on a wait list and given treatment after the research is concluded.
For the purpose of our research, Sapirstein and I were not particularly interested in the effects of the antidepressants or psychotherapy. What we were interested in was the placebo effect. But since we had the treatment data to hand, we looked at them as well. And, as it turned out, it was the comparison of drug and placebo that proved to be the most interesting part of our study.
All told, we analysed 38 clinical trials involving more than 3,000 depressed patients. We looked at the average improvement during the course of the study in each of the four types of groups: drug, placebo, psychotherapy and no-treatment. I am going to use a graph here (Figure 1.1, overleaf) to show what the data tell us. Although the text will have a couple more such charts, I am going to keep them to a minimum. But this is one that I think we need, to make the point clearly. What the graph shows is that there was substantial improvement in both the drug and psychotherapy groups. People got better when given either form of treatment, and the difference between the two was not significant. People also got better when given placebos, and here too the improvement was remarkably large, although not as great as the improvement following drugs or psychotherapy. In contrast, the patients who had not been given any treatment at all showed relatively little improvement.
The first thing to notice in this graph is the difference in improvement between patients given placebos and patients not given any treatment at all. This difference shows that most of the improvement in the placebo groups was produced by the fact that they had been given placebos. The reduction in depression that people experienced was not just caused by the passage of time, the natural course of depression or any of the other factors that might produce an improvement in untreated patients. It was a placebo effect, and it was powerful.
Figure 1.1. Average improvement on drug, psychotherapy, placebo and no treatment.2 ‘Improvement’ refers to the reduction of symptomson scales used to measure depression. The numbers are called ‘effect sizes’. They are commonly used when the results of different studies are pooled together. Typically, effect sizes of 0.5 are consideredmoderate, whereas effect sizes of 0.8 are considered large. So the graph shows that antidepressants, psychotherapy and placebos produce large changes in the symptoms of depression, but there was only a relatively small average improvement in people who were not given any treatment at all.
One thing to learn from these data is that doing nothing is not the best way to respond to depression. People should not just wait to recover spontaneously from clinical depression, nor should they be expected just to snap out of it. There may be some improvement that is associated with the simple passage of time, but compared to doing nothing at all, treatment - even if it is just placebo treatment - provides substantial benefit.
Sapirstein and I were not surprised to find that there was a powerful placebo effect in the treatment of depression. Actually, we were quite pleased. That was our hypothesis and our reason for doing the study. What did surprise us, however, was how small the difference was between the response to the drug and the response to the placebo. That difference is the drug effect. Although the drug effect in the published clinical trials that we had analysed was statistically significant, it was much smaller than we had anticipated. Much of the therapeutic response to the drug was due to the placebo effect. The relatively small size of the drug effect was the first of a series of surprises that the anti-depressant data had in store for us.
One way to understand the size of the drug effect is to think about it as only a part of the improvement that patients experience when taking medication. Part of the improvement might be spontaneous - that is, it might have occurred without any treatment at all - and part may be a placebo effect. What is left over after you subtract spontaneous improvement and the placebo effect is the drug effect. You can see in Figure 1.1 that improvement in patients who had been given a placebo was about 75 per cent of the response to the real medication. That means that only 25 per cent of the benefit of antidepressant treatment was really due to the chemical effect of the drug. It also means that 50 per cent of the improvement was a placebo effect. In other words, the placebo effect was twice as large as the drug effect.
The drug effect seemed rather small to us, considering that these medications had been heralded as a revolution in the treatment of depression - blockbuster drugs that have been prescribed to hundreds of millions of patients, with annual sales totalling billions of pounds.3 Sapirstein and I must have done something wrong in either collecting or analysing the data. But what? We spent months trying to figure it out.
ARE ALL DRUGS CREATED EQUAL? DOUBLE-BLIND OR DOUBLE-TALK
One thing that occurred to us, when considering how surprisingly small the drug effect was in the clinical trials we had analysed, was that a number of different medications had been assessed in those studies. Perhaps some of them were effective, whereas others were not. If this were the case, we had underestimated the benefits of effective drugs by lumping them together with ineffective medications. So before we sent our paper out for review, we went back to the data and examined the types of drugs that had been administered in each of the clinical trials in our meta-analysis.
We found that some of these trials had assessed tricyclic antidepressants, an older type of medication that was the most commonly used antidepressant in the 1960s and 1970s. In other trials, the focus was on selective serotonin reuptake inhibitors (SSRIs) like Prozac (fluoxetine), the first of the ‘new-generation’ drugs that replaced tricyclics as the top-selling type of antidepressant. And there were other types of antidepressants investigated in these trials as well. When we reanalysed the data, examining the drug effect and the placebo effect for each type of medication separately, we found that the diversity of drugs had not affected the outcome of our analysis. In fact, the data were remarkably consistent - much more so than is usually the case when one analyses different groups of data. Not only did all of these medications produce the same degree of improvement in depression, but also, in each case, only 25 per cent of the improvement was due to the effect of the drug. The rest could be explained by the passage of time and the placebo effect.
The lack of difference we found between one class of antidepressants and another is now a rather frequent finding in antidepressant research.4 The newer antidepressants (SSRIs, for example) are no more effective than the older medications. Their advantage is that their side effects are less troubling, so that patients are more likely to stay on them rather than discontinue treatment. Still, the consistency of the size of the drug effect was surprising. It was not just that the percentages were close; they were virtually identical. They ranged from 24 to 26 per cent. At the time I thought, ‘What a nice coincidence! It will look great in a PowerPoint slide when I am invited to speak on this topic.’ But since then I have been struck by similar instances in which the consistency of the data is remarkable, and it is part of what has transformed me from a doubter to a disbeliever. I will note similar consistencies as we encounter them in this book.
“[Kirsch’s] case that the drugs’ benefits are due to placebo and enhanced placebo effect is fascinating and demands urgent research…Clearly, it's time for a big rethink of what constitutes mental illness and about how to treat it.”
Literary Review (UK)
“[B]rilliantly subversive… a fascinating and disturbing book.”
Kelly Lambert, PhD, Professor of Psychology, Randolph-Macon College; President, International Behavioral Neuroscience Society; Author of Lifting Depression
“Considering the crude and nonspecific therapies that have been historically available for depression, the thought of a pill acting as an effective agent against the tumultuous symptoms of this disease was appealing to everyone in the mental health industry. But, as Irving Kirsch points out in this provocative and informative treatise, The Emperor’s New Drugs, this dream ultimately turned out to be a fairy tale. There was no prince of healing to provide the promised relief for patients. Kudos to Dr. Kirsch for his impressive scientific investigative reporting described in this book, forcing our attention away from the fairy tale and toward the reality of more effective treatment strategies for depression.”
David D. Burns, author of
Feeling Good: The New Mood Therapy
“A beautifully written, profoundly important book.”
Druin Burch, author of Taking the Medicine
“A terrific account of how optimism, greed and scientific incompetence have misled us about the nature of depression and the drugs we throw at it.”
“[The Emperor’s New Drugs] absolutely dismantles the case for antidepressants as a pharmacologically effective treatment.”
“Writing with a broad audience in mind, Kirsch expands on this important topic in a lively style with clear, cogent explanations of the science involved, and many examples of the differences between solid and flawed research. The result is a fascinating book with broad implications for science policy.”
St. Petersburg Times
“Measured and laserlike in focus…The Emperor's New Drugs dismantles the case for antidepressants as a pharmacologically effective treatment.”
“Kirsch…uses clear no-nonsense prose to marshal the extraordinary and convincing evidence needed to support his position.”
- On Sale
- Jan 26, 2010
- Page Count
- 240 pages
- Basic Books