How Effective Are Antidepressants?

In 1953 the Dean of Harvard Medical School, George Packer Berry, MD, told the students, “half of what is taught in medical school is wrong. The problem is that we don’t know which half.”

Since that time, his admonition has been repeated by many medical school leaders. Although medical knowledge has grown enormously over the last half century, there is still tremendous uncertainty about what works and what doesn’t.

Physicians are supposed to practice “evidence-based medicine.” To do that, they need to know that the procedures they perform and the drugs they prescribe have been carefully tested in well-designed clinical trials. They need to understand when a treatment is worthwhile and when it might be worthless or even harmful.

Sadly, many studies never get published, particularly the ones that show no benefit from the medication being tested. That makes it hard for doctors to evaluate all the evidence.

This was brought home in an article published in the New England Journal of Medicine (Jan. 17, 2008). Erick Turner, MD, and his colleagues reviewed studies of 12 antidepressant drugs. There were 74 studies that had been registered with the FDA, but roughly one third of them were not published.

When trials produced positive results they were reported as such 97 percent of the time. Only 8 percent of antidepressant trials that showed no effectiveness reported the negative findings.

When negative as well as positive antidepressant trials are analyzed together, something strange happens. The overall results turn out to be surprisingly disappointing.

A recent “meta-analysis” did just that [Public Library of Science (PLoS) Medicine, February, 2008]. Researchers obtained FDA studies under the freedom of information act (including unpublished research) for four antidepressants: Effexor, Paxil, Prozac and Serzone.

When the data was crunched the antidepressants turned out to be no more effective in relieving mild to moderate depression than sugar pills. Severely depressed patients did seem to benefit a bit from the drugs, but the investigators determined that this was probably more because the placebos stopped working rather than because patients were responding better to medication.

The authors concluded that, “Given these data, there seems little evidence to support the prescription of antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed.”

Antidepressants are among the most widely prescribed drugs in the world. Tens of millions of people take drugs like Effexor, Paxil and Prozac every day. They expect such medicine to work, especially since they are pricey. A month’s supply of Effexor or Prozac can cost more than $150.

Such drugs can also cause side effects such as nausea, headache, insomnia, nervousness, dizziness, dry mouth, rash, sweating and sexual dysfunction. Many patients would be willing to accept some of these symptoms if they were guaranteed relief from depression.

The new data, however, suggests that the benefits may be too uncertain to justify the risks. Physicians and patients deserve access to all the evidence so they can better determine what works and what doesn’t.