03/18/2011 01:44 pm ET Updated Dec 06, 2017

Why Do Clinical Trials Exclude Depressed People?

When the U.S. Food and Drug Administration announced in 2009 that Pfizer Inc's smoking-cessation drug Chantix would need to carry a restrictive "black box" warning label, the move didn't really surprise the market.

The drug's sales had already been declining. By the end of 2009, they had dropped to $700 million, down from $846 million the previous year.

"When this drug launched, a lot of people expected a blockbuster drug, with over $1 billion in sales, but then the reports of the side effects started coming in," Damien Conover, an analyst with Morningstar, told Reuters Health.

The FDA's response came after hundreds of reports of erratic behavior and several suicides. Now, Pfizer faces a civil lawsuit involving at least 1,200 patient complaints.

In retrospect, experts say all of this could have been avoided -- or at least predicted -- had the company's clinical trials been designed differently. Pfizer tested Chantix on thousands of smokers in order to get FDA approval, but the clinical trials excluded people with depression.

That's despite the fact that the disorder is especially common among smokers: More than 40 percent of smokers are depressed, compared to just 7 percent of the general population, according to statistics from the Centers for Disease Control and Prevention and the National Institute of Mental Health.

Doctors have long known that depression often coincides with other disorders, such as addiction and heart disease. Yet clinical trials for these related conditions routinely exclude patients with depression.

This strategy may benefit drug companies during the early testing stages, but it can backfire once the treatment is released into the real world.

"Adherence is often an issue with depressed participants," said Dr. Anne Thorndike, an internist who studies smoking cessation at Massachusetts General Hospital in Boston. "But how generalizable can the results be if depression is excluded?"


Pfizer's decision to exclude smokers with depression was not unusual, and was within FDA guidelines.

Sanofi-Aventis did the same thing with the weight loss drug rimonabant (Acomplia) and saw the drug banned in Europe after being linked to suicide shortly after it was approved there a few years ago.

Last summer, an FDA panel rejected Boehringer Ingelheim's "female Viagra" drug, flibanserin, in part because it wasn't tested on women with depression. The company discontinued work on the drug a few months later.

A recent search by Reuters Health of the federally run database revealed the practice is common in smoking cessation studies.

Of 38 actively recruiting large-scale late-stage studies known as Phase 3 clinical trials, 21 excluded people with mental illness, and 10 did so for depression specifically.

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