The makers of antidepressants like Prozac and Paxil never published the results of about a third of the drug trials that they conducted to win government approval, misleading doctors and consumers about the drugs’ true effectiveness, a new analysis has found.

In published trials, about 60 percent of people taking the drugs report significant relief from depression, compared with roughly 40 percent of those on placebo pills. But when the less positive, unpublished trials are included, the advantage shrinks: the drugs outperform placebos, but by a modest margin, concludes the new report, which appears Thursday in The New England Journal of Medicine.

Previous research had found a similar bias toward reporting positive results for a variety of medications; and many researchers have questioned the reported effectiveness of antidepressants. But the new analysis, reviewing data from 74 trials involving 12 drugs, is the most thorough to date. And it documents a large difference: while 94 percent of the positive studies found their way into print, just 14 percent of those with disappointing or uncertain results did. 

http://www.nytimes.com/2008/01/17/health/17depress.html?_r=1&ex=1358226000&en=b9becee3f0d749dd&ei=5088&partner=rssnyt&emc=rss

The researchers obtained unpublished data on the more recently approved drugs from the F.D.A.’s Web site. For older drugs, they tracked down hard copies of unpublished studies through colleagues, or using the Freedom of Information Act. They checked all of these studies against databases of published research, and also wrote to the companies that conducted the studies to ask if specific trials had been published.

They found that 37 of 38 trials that the F.D.A. viewed as having positive results were published in journals. The agency viewed as failed or unconvincing 36 other trials, of which 14 made it into journals.

But 11 of those 14 journal articles “conveyed a positive outcome” that was not justified by the underlying F.D.A. review, said the new study’s lead author, Dr. Erick H. Turner, a psychiatrist and former F.D.A. reviewer who now works at Oregon Health and Sciences University and the Portland Veterans Affairs Medical Center. His co-authors included researchers at Kent State University and the University of California, Riverside.

For the study, Hen and colleagues needed to reach serotonin receptors in just the right part of the brain.

To do this, the team used mice that were genetically altered to have fewer serotonin receptors only in the region where the serotonin-producing raphe neurons are located.

Once the team had mice that had different levels of serotonin receptors in different parts of the brain, they did a behavior test that assesses boldness when mice get food in a brightly lit area.

Mice on antidepressants usually become more daring, but the drugs had no such effect on mice with surplus serotonin receptors.

"The most dramatic finding is that the mice that have high levels of receptors in these serotonin neurons do not respond to fluoxetine or Prozac," Hen said.

But when they reduced the number of these receptors -- or molecular doorways -- they were able to reverse the effect, he said.

"By simply tweaking the number of receptors down, we were able to transform a non-responder into a responder," Hen said. At least 27 million take antidepressants in the United States, nearly double the number that did in the mid-1990s

Decisive Moments

I am listening.

When I can do

nothing else

I can at least listen.

I feel detached floating,

I listen to the wind howling

and the fiery leaves it scatters.

I listen to the spring water

rushing through the boulders

cooling the air at the bridge.

I listen to that all familiar voice

to hear how

what I am thinking

sounds like from the other side

of my head

I can not explain the way

my mind feels going through

the motions.

When I can do nothing else

I can at least listen.

I feel detached floating,

not that feel good ease

float, more that suspended

sensory deprivation

could freak out float.

Decisive moments.

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