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Do antidepressants actually work better than placebo?

antidepressants

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Scientists have been debating the efficacy of antidepressants for decades. The latest paper to throw its hat into the ring concludes that there is little evidence to show that they perform better than placebos. Let’s find out more.

What is a placebo?

A placebo is a substance, such as a pill or shot, that doesn’t contain any active medicine. Scientists typically use placebos as controls in research studies. This helps them understand how much of a medicine’s effects are due to the drug itself, versus how much are due to participants’ expectations or other factors.

The placebo effect, and its underlying psychobiology, has also been extensively studied in the treatment of major depression.

Generally, people who are given a placebo may report improvements in symptoms, sometimes even when they know they’re taking something that doesn’t contain real medicine. The placebo effect, and its underlying psychobiology has also been extensively studied in the treatment of major depression.

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Not surprisingly, placebo effects are also affected by a patient’s previous treatment for depression, individual genetics, and his or her idiosyncratic personality features. It is a widely held belief in the mental health community that some people are more genetically predisposed to psychopathology, including disorders that influence the rewarding effects of illicit drugs, gambling, and other pleasurable activities.

Depression and its manifestations

Depression (major depressive disorder) is a common and serious medical illness that negatively affects how you feel, the way you think and how you act. Fortunately, it is also treatable. Depression causes feelings of sadness and/or a loss of interest in activities once enjoyed, however, being sad is not the same as having depression.

Hallmark or gateway symptoms of clinical depression can include, but are not limited to the following:

  • Feeling down or depressed most of the day, nearly every day, for two weeks or more (decreased mood)
  • A lack of pleasure from interests or activities that were previously enjoyed (also called anhedonia)
  • A significant change in sleep patterns (either increased or decreased)
  • A marked change in diet and eating habits (either increased or decreased appetite and food consumption)
  • Feelings of either being more agitated and restless or, conversely, more sluggish and “heavy”
  • An impaired ability to concentrate on tasks related to school, work, or household-related activities

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Current use of antidepressants

In 2017, around 17.3 million adults in the United States experienced an episode of major depression. Alongside talking therapies such as psychotherapy, many people with depression take antidepressants.

Depression is a common and serious medical illness that negatively affects how you feel, the way you think and how you act.

According to the Centers for Disease Control and Prevention (CDC), a 2011–2014 survey found that 12.7% of U.S. individuals aged 12 or above had taken antidepressant medication in the previous month.

That equates to almost 1 in 8 people. Of these individuals, one-quarter had been taking antidepressants for at least 10 years. Although many people use these drugs, there is still a great deal of controversy surrounding how well they work — and studies have generated conflicting results.

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Why the doubt?

To a greater or lesser degree, all the factors below and more have combined to produce a situation where scientists are still not clear whether antidepressants work better than a placebo:

  • Pharmaceutical companies are keen to market the drugs they have spent years designing and testing.
  • Doctors want to provide medication to those with a reduced quality of life.
  • Patients are keen to try anything that might improve their well-being.
  • Journals are more likely to publish studies with positive findings.

The latest analysis to form part of this ongoing battle comes from scientists at the Nordic Cochrane Centre in Denmark. This time, the authors conclude that the current level of evidence in support of antidepressants is not sufficient to prove that they work better than placebo.

Although many people use these drugs, there is still a great deal of controversy surrounding how well they work — and studies have generated conflicting results.

The review, which now appears in BMJ Open, is a response to a paper by Dr. Andrea Cipriani and team that The Lancet published in February 2018. In the paper, Dr. Cipriani and team compared the performance of 21 antidepressants.

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They set out to “compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder,” as a guide for doctors. Their analysis was the largest of its kind; it included 522 trials and 116,477 participants. The researchers concluded that, among other things, “[a]ll antidepressants were more efficacious than placebo in adults with major depressive disorder.”

For many, these findings were definitive proof that antidepressants work. However, “[t]he review received widespread media coverage, largely citing it as finally putting to rest any doubts regarding the efficacy of antidepressants,” explain the authors of the latest BMJ Open paper.

Reopening the data

Led by Dr. Klaus Monkholm, the authors of the new publication believe that the earlier work by Dr. Cipriani did not address certain biases in the data. Dr. Monkholm and others initially penned a critique in The Lancet in September 2018.

In it, the authors outline a number of issues. For instance, in an ideal study, participants are “blinded.” This means that they do not know whether they are receiving the drug or the placebo.

However, because antidepressants have well-known side effects, it is very difficult to conduct studies wherein participants are adequately blinded; in other words, participants are likely to know that they are in the experimental group rather than the placebo group.

Dr. Monkholm and his team believe that Dr. Cipriani did not adequately account for this. Because so many people use antidepressants, the scientists decided to go beyond the critique. They set out to repeat Dr. Cipriani’s analysis, but this time, they would account for the biases they believe the team missed the first time.

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