Placebo effect depressants

The neural mechanisms underlying the placebo effect are only partially understood and most of our knowledge comes from pain, although recently Parkinson s disease, immune and endocrine responses, and depression have emerged as interesting models (Fig. 1). In each of these... 

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 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 41 examine the chemical-imbalance theory. You may be surprised to leam 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 chem-... 

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 1 examine the placebo effect itself. 1 look at the myriad of effects that placebos have been shown to have and explore the theories of how these effects are produced. 1 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. 

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. 

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... 

When Schildkraut introduced the monoamine theory of depression, he admitted that there was little direct evidence for it. Instead, it was based on the supposed effectiveness of antidepressant medication and the mistaken belief that reserpine makes people depressed. Schildkraut acknowledged that Most of this evidence is indirect, deriving from pharmacological studies with drugs such as reserpine, amphetamine and the monoamine oxidase inhibitor antidepressants which produce affective changes. 21 A half-century has passed since his chemical-imbalance theory of depression was introduced, and the presumed effectiveness of antidepressants remains the primary evidence in its support. But as we have seen, the therapeutic effects of antidepressants are largely due to the placebo effect, and this pretty much knocks the legs out from under the biochemical theory. 

I suppose that some ingenious minds will be able to find a way of accommodating the chemical-balance hypothesis to these data, but I suspect that the accommodation will require convoluted circumventions, like those used by the Flat Earth Society in their efforts to maintain their defunct theory in the face of photographic evidence from space. If depression can be equally affected by drugs that increase serotonin, drugs that decrease it and drugs that do not affect it at all, then the benefits of these drugs cannot be due to their specific chemical activity. And if the therapeutic benefits of antidepressants are not due to their chemical composition, then the widely proffered chemical-imbalance theory of depression is without foundation. It is an accident of history produced serendipitously by the placebo effect. 

The biochemical theory of depression is in a state of crisis. The data just do not fit the theory. The neurotransmitter depletion studies that I described earlier in this chapter show that lowering serotonin or norepinephrine levels does not make most people depressed. When administered as antidepressants, drugs that increase, decrease or have no effect on serotonin all relieve depression to about the same degree. And the effect of anti-depressants, which was the basis for proposing the chemical-imbalance theory in the first place, turns out to be largely a placebo effect. 

If the chemical-imbalance theory is wrong, and if depression is not a brain disease, how is it produced and how can it be prevented and treated One way to look for clues is to examine the process by which we were misled into the realm of chemistry. There is a culprit hiding in the history of the chemical-imbalance theory - a culprit that is guilty of leading doctors and patients astray over and over again in the history of medicine. The culprit is the placebo effect, and its darker twin, the nocebo effect. Depressed people got better when given MAO and reuptake inhibitors as antidepressants, and this led researchers to conclude that depression must be caused by a chemical deficiency. But much (if not all) of that improvement turns out to be a placebo effect. So to understand depression and how it might be treated effectively, we need to examine the placebo effect more carefully. That is the topic of the next two chapters. 

How can this be How is it possible that a dummy pill with no active ingredients can produce substantial improvement in a condition as serious as clinical depression As it turns out, placebos can be surprisingly effective, not only in the treatment of depression, but also for various other conditions. As we shall see in this chapter, placebos can reverse the effects of powerful medications. They can affect the body as well as the mind. They produce side effects as well as beneficial effects. They can make people feel sick, and they can make them feel better. Placebo effects are part of a broader phenomenon - the power of suggestion to change how people feel, how they behave, and even their physiology. If placebos can produce such powerful effects, it is important to understand them. Only by unlocking the secrets of the placebo effect can we hope to harness its power so that it can be used in clinical practice. In this chapter we look at the power of the placebo its ability to produce therapeutic change and to cause harm. 

One of the factors that determine the effectiveness of a placebo is the nature of the condition being treated. Conditions that have a strong psychological component - such as pain, anxiety and depression - are particularly prone to placebo influence, whereas conditions like bone fractures, diabetes and infertility are less likely to be affected by placebo treatment. But this does not mean that placebo effects are all in the mind . Placebos affect physiology as well as psychology. 

Depression is not the only clinical condition in which placebo effects have been linked to changes in the brain. Changes in brain activity have also been shown in neuroimaging studies of placebo analgesics, the most influential of which was reported by a team of researchers led by Tor Wager, a neuroscientist at Columbia University who, at the time he conducted these studies, was a postgraduate student at the University of Michigan.39... 

The evidence I have reviewed in this chapter indicates that placebos work for a wide variety of conditions. They can produce both positive and negative effects. They affect the body as well as the mind. They can be as strong as potent medications, and their effects can be lasting. We have also seen that placebos can produce negative effects. Furthermore, the nocebo effect maybe an important factor in clinical depression - at least for some depressed people. For this reason, understanding the placebo effect is essential to understanding how to treat depression effectively. How do inert substances produce both therapeutic and detrimental effects Chapter 6 provides an answer to this question. 

If we are to harness the placebo effect and make use of it in clinical practice, we first have to understand how it works. A number of factors have been proposed as explanations of the placebo effect. These include the relationship between doctors and patients, the patient s beliefs and expectations, the production of opiates in the brain, and a phenomenon called classical conditioning, in which people come to associate pills and injections with therapeutic effects, just as Pavlov s dogs came to associate the sound of a bell with the presentation of food. In this chapter we look at how all of these processes combine to produce placebo effects, and we consider their implications for the treatment of depression. 

If you look in the medical literature, you will often see the term placebo defined as a non-specific treatment. What does it mean to say that a treatment is not specific It could mean that the treatment is effective for many different disorders, rather than for only one particular condition. In this sense, placebos are indeed non-specific. Besides depression, placebos have been shown to affect anxiety, pain, ulcers, irritable bowel syndrome, Parkinson s disease, angina, autoimmune diseases, Alzheimer s disease, rheumatoid arthritis, asthma, gastric function, sexual dysfunction and skin conditions. We know this from the thousands of studies in which placebos have been used as control conditions, against which the effects of medication have been evaluated, and from studies that were specifically designed to assess the placebo effect. 

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