Antidepressant Safety Debate May Include Adult Patients
By BENEDICT CAREY
Published: February 18, 2005
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The yearlong debate over whether antidepressant drugs increase the risk of
suicide in some children may soon widen to include adults, as English and
Canadian scientists are reporting findings from three new analyses of
suicide risk in people over age 18 who have taken the medications.
The new findings are mixed, and apparently contradictory, and likely to
encourage both patient advocates who believe that antidepressants like
Prozac have hidden dangers, and manufacturers who insist that the
medications are safe, experts said.
One of the reports, an analysis of data on antidepressants from previous
studies, found that adults taking the drugs were twice as likely to attempt
suicide as those receiving a dummy pill or other treatments, but no more
likely to complete the act.
The two other reports found no significant link between the medications and
suicide. Suicide attempts occurred in less than 0.5 percent of the more than
200,000 people included in the three studies.
All three papers appeared yesterday in the online version of The British
"There has been a phenomenal amount of pressure to study this issue in
adults," in part because of the debate over the risk in children, said Dr.
John Geddes, a professor of epidemiological psychiatry at Oxford University
and the co-author of an accompanying editorial in the journal. Dr. Geddes
was not involved in the studies and has received research money from drug
"We know a certain amount of negative evidence on these drugs has been
suppressed, and the more information we have on them in the public domain,
the better to guide clinical practice," he said.
In the early 1990's, a panel of experts convened by the Food and Drug
Administration concluded that there was not enough evidence to link drugs
like Prozac and Zoloft to increased suicide risk and most psychiatrists say
that the drugs are more likely to prevent suicide.
But regulators in the United States and Britain recently issued warnings
that the drugs, known as selective serotonin reuptake inhibitors, or
S.S.R.I.'s, could raise the risk of suicidal thinking in a small number of
children and adolescents. The F.D.A. is scrutinizing suicide attempts by
adults reported in drug trials.
The risk is extremely difficult to determine, experts say, in part because
suicide attempts are rare.
In one of the new analyses, researchers at the University of Ottawa
re-evaluated data from 345 antidepressant trials for depression and other
conditions, involving 36,455 men and women. The investigators found 143
total suicide attempts, and found that the rate was twice as high in people
who were taking S.S.R.I.'s as it was in those getting placebo pills, or some
other form of therapy.
"Many people are on these drugs, which makes the rare risk very important,"
said Dr. Dean Fergusson of the University of Ottawa, who is a lead author of
Dr. David A. Freedman, a clinical trials expert and statistician at the
University of California, Berkeley, who was not involved in any of the
studies, said that reviews of this kind are not a very reliable way to
determine risks. Moreover, he said, the Ottawa study presumed that all
antidepressants affected everyone the same way in terms of suicide risk.
"This is like saying your reaction to Prozac is the same as mine to Zoloft,
which we know isn't true," he said. "This assumption exaggerates the
significance of their findings."
Dr. Fergusson disagreed, saying the assumption of uniform effect gave a
In another analysis, also in the British journal, doctors evaluated data
from 477 trials involving 40,826 people, which were submitted by drug
companies to British regulators for safety review. "We found no evidence
that S.S.R.I.'s increased the risk of suicide," and weak evidence that the
drugs increased the risk of self harm, the authors concluded.
The third study analyzed case records of 146,095 people prescribed
antidepressants for the first time from 1995 to 2001. The researchers found
no evidence of increased suicide risk in adults taking S.S.R.I.'s compared
with people of the same age and similar histories taking other types of
Given that studies report suicidal behavior in a number of ways, experts are
skeptical that reviews of trial data will resolve the issue. "We have
machinery to pull diamonds from the earth, but we don't have machinery to
pull truth from data in these studies," Dr. Freedman said.
Psychiatrists said the studies were not likely to change how they treat
patients: the drugs tend to increase agitation and unusual behavior in the
first few weeks after the treatment is started, when patients need to be
closely monitored, they said.