Do Anti-Depressants Work? It Very Well Might Be the Placebo That Does the Trick

Psychologist Irving Kirsch unveils the ineffectiveness of antidepressants and suggests there's more to the placebo effect than once imagined.

The following is an excerpt from The Emperor's New Drugs: Exploding the Antidepressant Myth by Irving Kirsch, Ph.D. Available fromBasic Books, a member of the Perseus Books Group. Copyright © 2011.

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 percent 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. 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."

When I began my research, 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.

Whereas hopelessness is a central feature of depression, hope lies at the core of the placebo effect. Placebos instill hope in patients by promising them relief from their distress. Genuine medical treatments also instill hope, and this is the placebo component of their effectiveness. When the promise of relief instills 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.

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 analyzed were not the only studies assessing the effectiveness of antidepressants. I discovered that approximately 40 percent 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 analyzed 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.

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 analyzed 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.

Evidence that was known to the pharmaceutical companies and to regulatory agencies 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 analyzed the data and submitted the results for peer review to medical and psychological journals, where they were then published.

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.

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. We seem to be on the cusp of a revolution in the way we understand and treat depression.

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Dr. Irving Kirsch is professor of psychology at the University of Hull, UK, and professor emeritus at the University of Connecticut. His research has been published in the British Medical Journal as well as the New York Times, Newsweek, and more.
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