Thursday, September 17, 2015

Oh wait, Paxil is no better than placebo in teens, and it increases suicide risk

More generally, you know what stinks about these clinical drug trials for antidepressants? Their use of the terribly lame HAM-D as the primary outcome measure. I suspect that they don't use the MMPI-2 because the scores would be too stable from Time 1 to Time 2.

"Fourteen years ago, a leading drug maker published a study showing that the antidepressant Paxil was safe and effective for teenagers. On Wednesday, a major medical journal posted a new analysis of the same data concluding that the opposite is true.
That study — featured prominently by the journal BMJ — is a clear break from scientific custom and reflects a new era in scientific publishing, some experts said, opening the way for journals to post multiple interpretations of the same experiment. It comes at a time of self-examination across science — retractions are at an all-time high; recent cases of fraud have shaken fields as diverse as anesthesia and political science; and earlier this month researchers reported that less than half of a sample of psychology papers held up....
...The dispute itself is a long-running one: Questions surrounding the 2001 study played a central role in the so-called antidepressant wars of the early 2000s, which led to strong warnings on the labels of Paxil and similar drugs citing the potential suicide risk for children, adolescents and young adults. The drugs are considered beneficial and less risky for many adults over 25 with depression.
Over the years, thousands of people taking or withdrawing from Paxil or other psychiatric drugs have committed violent acts, including suicide, experts said, though no firm statistics are available. Because many factors could have contributed to that behavior, it is still far from clear who is at risk — and for whom the drugs are protective....

...The original study began in the late 1990s, when antidepressant makers started testing the drugs in young people. Antidepressant trials are an extremely tricky enterprise, in part because anywhere from a third to more than half of subjects typically improve on placebo. Choices about how to measure improvement — and how to label side effects — can make all the difference in how good a drug looks.
And so it was in the Paxil study. The original research, led by Dr. Martin Keller of Brown University, tracked depression scores over eight weeks in three groups of about 90 adolescents each, one taking Paxil, one on placebo pills and one taking imipramine, an older generic drug for depression. The Paxil group did no better than the other two groups on the study’s main measure — a standard depression questionnaire — but did rate higher on other, “secondary” measures, like another scale of mood problems, the authors reported.
Researchers consider secondary measures like these as akin to circumstantial evidence, potentially meaningful but not as strong as the primary ones....
...Prescriptions of antidepressants to young people surged in the wake of the study, increasing by 36 percent between 2002 and 2003, according to one analysis. The growth slowed after regulators ordered the black-box warnings on labels.
...The reanalysis delivers the same critique as before — no clear effectiveness, and mislabeling of serious side effects — only from the inside, using voluminous data from the study itself. ...
...In an interview, Dr. Healy said that five of six adverse events labeled “emotional lability” in the original study involved suicidal thinking or behavior but were not presented as such. The patient-level files provided detail on what, exactly, happened in those cases: One teenager was hospitalized after taking 80 Tylenol tablets. Another overdosed on Paxil and other medications after a “disagreement with her mother.” Others suffered “severe suicidal ideation,” and one was “admitted due to severe suicidal and homicidal ideation, towards his parents.” No completed suicides occurred."

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