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Antidepressants have been heralded as miracle drugs that have changed the lives of millions of people. Depression, we are told, is an illness – a disease of the brain that can be cured by medication. But what exactly is the evidence for this? Could it be that we've been misled?
According to drug companies, more than 80% of depressed patients can be treated successfully. Claims like this have made antidepressants such as Prozac among the most widely prescribed drugs in the world, with sales that top US$12 billion a year in the United States alone.
The companies claim that the effectiveness of antidepressants has been proven in published clinical trials showing that the drugs are significantly better than placebos.
But a closer look at the data tells a different story. Many depressed patients improve when given medication, but so do many given a placebo. The difference between the drug response and the placebo response is not all that great.
Many effects of antidepressants seem to be due to the placebo effect. And the published trials are only the tip of the iceberg of material that normally doesn't see the light of day. There are also clinical trials that have not been published. These are studies that have failed to show a significant benefit from taking the drug.
When all of the data sets are combined – published and unpublished – the inescapable conclusion is that antidepressants may be little more than active placebos, drugs with very little specific therapeutic benefit, but with serious side effects.
This conclusion is based on scientific studies, some of which became publicly accessible when my colleagues and I obtained and analysed all of the clinical trial data submitted to the U.S. Food and Drug Administration (FDA) by the manufacturers of the most widely prescribed antidepressant medications.
There are great advantages to analysing the FDA data set. One is that it includes both unpublished and published studies. Many clinical trials – especially ones that were not successful– are not published. This leads to what has been termed the 'publication bias'.
So if you are limited to examining the published literature, you will be likely to overestimate the effect of the drug you are reviewing. By analysing a complete data set, my colleagues and I have been able to avoid this bias.
The trials in the FDA data set all use the Hamilton Rating Scale for Depression as their primary measure of drug effectiveness, and the U.S. National Institute for Health and Clinical Excellence has used it to set cut-offs for establishing clinical significance. Having Hamilton scores for the trials meant that we could interpret the results in terms of how meaningful the drugs are in people's lives.
Using the FDA data, we found that 82% of the response to medication was also produced by the placebo. More importantly, the overall drug effect from trials sponsored by the drug companies was not clinically significant.
The only patients for whom the drug-placebo difference was significant were those whose depression was extremely severe. Even with these patients, it was not that the drug was more effective, but rather the placebo was less effective.
Depression is often portrayed as a brain disease – the result of a chemical imbalance in the brain. Most people are unaware that there is little direct evidence for the chemical imbalance theory. Instead, it is based largely on the supposed effectiveness of antidepressant medication.
If changes in neurotransmission can cure depression, it was argued, then depression could be due to a malfunctioning brain.
However, the effects of antidepressants are not that great – they are not dose-dependent (a small dose of Prozac is just as effective as a large dose) and drugs with different chemical effects produce the same results. This suggests that the benefits of antidepressants are not due to their specific chemical activity.
If therapeutic benefits of antidepressants are not due to their chemical composition, this casts doubt on current biochemical theories of depression.
Antidepressants may be of specific benefit to the most severely depressed patients, but for most, the response to antidepressant drugs is largely placebo.
Fortunately, there are many alternative treatments that have been found to be effective in controlled clinical research. In particular, psychotherapy has been found to be as effective in the short run and more effective in the long run.
Irving Kirsch is a professor of psychology and specialist on the placebo effect at the University of Hull in England. He is author of the The Emperor's New Drugs.
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