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?"

COMMON PROBLEM

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 ClinicalTrials.gov 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.

Copyright 2011 Thomson Reuters. Click for Restrictions.

Comments

[Joseph Burgo PhD]

02:29 PM on 03/21/2011

In the case of Pfizer, my guess is that the company understood that depressed patients would have a much harder time quitting smoking, even with the aid of medication; they therefore excluded that sub-group from trials in order to prevent its results from being skewed and running the risk that the data would show no statistical improvement from Chantix. I'm no statistician so maybe I'm wrong. Maybe if the depressives were randomized to the differing test groups, this variable could be controlled.

But since depression is so widespread, and depressives are likely one of the groups most in need of help to quit smoking, it seems perverse and strange to exclude them as subjects in the testing process.

Joseph Burgo PhD
http://www.afterpsychotherapy.com

[SithRose]

09:25 PM on 03/21/2011

Well, Chantix specifically also has some of the most horrible side effects it's ever been my displeasure to experience.

Sure, it works. If you can get past the screaming horrific nightmares, the doubled-over-in-agony stomach pain...I've heard of chemo drugs with less unpleasant side effects.

[snaggle2th]

11:23 AM on 03/20/2011

How depressing....

[onionboy]

01:06 PM on 03/19/2011

The reason is practical. Clinical trials require that the majority of participants take all of their meds and remain on the trial through it's duration. When not enough research patients do this, both side effects and efficacy are under-reported.

Many reasons for dropping from a study early can be used as data points, such as side effects or a worsening of the underlying disease being studied. However, just about everything else makes the data from the research patient unevaluable. What that means, is that even when they're not overtly excluded, their data still might not be analyzed. So, simply removing the exclusion criteria is not the answer.

I'm not justifying that things should remain status quo. This does need to be re-examined. I just want people to understand the underlying issues.

[robin360]

08:02 PM on 05/06/2011

Good points. Also, depressed people are more likely to commit suicide than the general population. No drug company wants to explain that.

[Peace Walker]

04:22 AM on 03/19/2011

Nationalize big pharma now!

[JOHNSPEAKS]

09:42 PM on 03/18/2011

Drug companies and research scientists and mental health professionals all have one thing in common they will do -Anything- to keep their never ending -Ponzi Scheme- in business? Think twice before -You- get involved with the mental health industry and if -You- want proof just research the history of the mental health industry for the last hundred years and you will run from these supposed professionals???

[robin360]

08:00 PM on 05/06/2011

Thank you, Scientology spokesperson.

[UPD WAZU]

01:49 PM on 03/18/2011

"Why Do Clinical Trials Exclude Depressed People?"

Ummm, cuz they're such a downer to be around?

[mssreader]

08:30 PM on 03/18/2011

UPD, you are aware that most of them can't help it don't you? Please be nice to depressed people because they want to be happy too.