Oregon: A new analysis reported in JAMA Psychiatry raises serious
questions about the increasingly common use of second-generation
antidepressant drugs to treat anxiety disorders. It concludes that studies supporting the value of these medications
for that purpose have been distorted by publication bias, outcome
reporting bias and “spin.” Even though they may still play a role in
treating these disorders, the effectiveness of the drugs has been
overestimated.
In some cases the medications, which are among the most widely
prescribed drugs in the world, are not significantly more useful than a
placebo.
The findings were made by
researchers from Oregon State University, Oregon Health & Science
University, and the University of Groningen in The Netherlands. The work
was supported by a grant from the Dutch Brain Foundation.
Publication bias was one of the most serious problems, the
researchers concluded, as it related to double-blind, placebo-controlled
clinical trials that had been reviewed by the U.S. Food and Drug
Administration. If the FDA determined the study was positive, it was
five times more likely to be published than if it was not determined to
be positive.
Bias in “outcome reporting” was also observed, in which the positive
outcomes from drug use were emphasized over those found to be negative.
And simple spin was also reported. Some investigators concluded that
treatments were beneficial, when their own published results for primary
outcomes were actually insignificant.
“These findings mirror what we found previously with the same drugs
when used to treat major depression, and with antipsychotics,” said
Erick Turner, M.D., associate professor of psychiatry in the OHSU School
of Medicine, and the study’s senior author. “When their studies don’t
turn out well, you usually won’t know it from the peer-reviewed
literature.”
This points to a flaw in the way doctors learn about the drugs they prescribe, the researchers said.
“The peer review process of publication allows, perhaps even
encourages, this kind of thing to happen,” Turner said. “And this isn’t
restricted to psychiatry – reporting bias has been found throughout the
medical and scientific literature.”
Craig Williams, a professor in the Oregon State University/Oregon
Health & Science University College of Pharmacy, and co-author of
the study, said that “most of these drugs are fairly safe and
well-tolerated, but if a medication is less effective than believed,
this still raises serious questions about its use.
“The level of bias we found did not change the fact that some
antidepressants can have value in treating anxiety disorders,” Williams
said. “However, there is less evidence for value of these drugs than
published studies would have you believe. And these concerns are
increased when such medications are frequently prescribed by general
practitioners with less training in psychiatry.”
In this study, the researchers examined a broad body of the evidence
and scientific research that had been presented to the Food and Drug
Administration, including studies that had been done but were not
published in open scientific literature. They found that negative data
on drug efficacy tended not to get published, or was de-emphasized when
it was published.
Conclusions might have been manipulated or exaggerated because
positive results receive more scientific attention, are published
sooner, and lead to higher sales of a drug, said Annelieke Roest, the
lead author of the publication at the University of Groningen.
“Lots of research is funded eventually by the taxpayer, and that’s
reason enough to say that scientists should publish all their results,”
Roest said.
The study reiterated this point, and the need to more routinely publish nonsignificant results.
“There is strong evidence that significant results from randomized
controlled trials are more likely to be published than nonsignificant
results,” the researchers wrote in their study. “As a consequence, the
published literature . . . may overestimate the benefits of treatment
while underestimating their harms, thus misinforming clinicians, policy
makers and patients.”
Antidepressants are now widely prescribed for conditions other than
depression, the study noted. They are being used for generalized
anxiety, panic disorder, social anxiety, post-traumatic stress disorder
and other uses. In both the U.S. and Europe, use of antidepressant drugs
has significantly increased in the past two decades, the researchers
said, with much of that use driven by non-specialists in primary care
settings.
The level of reporting bias in the scientific literature, the
researchers wrote, “likely impacts clinicians’ perceptions of the
efficacy of these drugs, which could reasonably be expected to affect
prescription behavior.”