WASHINGTON -- Adults taking popular antidepressants such as
Prozac, Paxil and Zoloft are more than twice as likely to
attempt suicide as patients given sugar pills, according to
an analysis released Thursday of hundreds of clinical trials
involving tens of thousands of patients.
The results mirror a recent finding of the Food and Drug Administration
that the drugs increase suicidal thoughts and behavior among
some children and offer tangible support to concerns going
back 15 years that the mood-lifting pills have a dark side.
The examination of 702 controlled clinical trials involving
87,650 patients is the most comprehensive look at the subject
and is particularly telling because it counted suicide attempts
and included patients treated for a variety of conditions,
including sexual dysfunction, bulimia, panic disorder and
depression.
Experts cautioned, however, that the risks should be balanced
against the drugs' benefits. They have been shown to be effective
against depression and a host of other disorders in adults,
a positive track record largely missing in tests of the drugs
on children.
Adults with severe depression should continue to be considered
for drug treatment, but those with milder symptoms should
probably not be medicated, said John Geddes, professor of
epidemiological psychiatry at Oxford University, who wrote
a commentary accompanying the studies.
"For a lot of time, these drugs were seen as a panacea for
low mood in general," he said in a telephone interview. "We
do need to ensure they are only prescribed for patients with
clearly diagnosed depressive disorders."
The new study is certain to add to the controversy over the
class of drugs known as selective serotonin reuptake inhibitors,
or SSRIs. Following the arrival of Prozac in 1988, these drugs
have transformed psychiatry in the United States, even as
persistent critics have warned that their benefits were hyped
and their risks ignored. A spate of lawsuits in recent years
have claimed that the drugs were responsible for violent and
suicidal behavior.
New analyses of clinical trials in children last year prompted
FDA to require a prominent black box warning on labels that
the medications could increase the risk of suicide. The warning
refers only to children but is given to all patients.
American psychiatrists continue to strongly back SSRI drugs.
Groups such as the American Psychiatric Association say that
fears of drug-induced suicide are vastly exaggerated and that
untreated depression carries a far greater risk of suicide.
"If these medications were really increasing the incidence
of suicide attempts, you would think we would be seeing more
completed suicides," said David Fassler, an APA trustee and
psychiatrist in Burlington, Vt. "In fact, we are seeing exactly
the opposite."
Adolescent suicide rates have dropped 25 percent since the
early 1990s, even as more than a million children were put
on the drugs, Fassler said. Although no one can say for sure
what the connection is between those two trends, Fassler said,
"if the medications were significantly increasing the risk
of suicide, it is unlikely we would be seeing this kind of
decline over time."
The new analysis seems likely to deepen transatlantic divisions
over how the drugs are perceived and prescribed: British authorities
last year recommended that depressed patients who were able
to function at home and work should not be medicated right
away, but should be counseled to try exercise, self-help,
talk therapy -- or watchful waiting.
David Healy, a psychiatrist at the University of Wales who
helped conduct the new study, said managed-care insurance
companies in the United States were not likely to look kindly
upon physicians who monitor patients without prescribing drugs.
Healy prescribes the drugs but has long raised red flags about
them. He asked Thursday why scientists at the FDA and research
universities had not previously conducted this analysis, given
that the data have long been available.
"For whatever reason, an awful lot of people didn't want to
think there was a risk," he said.
FDA officials have said they are conducting an independent
analysis.
The new study was conducted by epidemiologist Dean Fergusson
and his colleagues at the Ottawa Health Research Institute
and included scientists from McGill University. It is published
in the current issue of the British Medical Journal along
with two related articles and a commentary by Geddes and University
of Verona psychiatrists Andrea Cipriani and Corrado Barbui.
Complicating the picture is the fact that suicide is rare
-- meaning that it takes very large studies to yield definitive
results. Fergusson's meta-analysis pooled data from a large
number of studies in the same manner as the recent FDA analysis
involving children's trials.
The American Psychiatric Association's Fassler said such an
approach could miscount the number of attempted suicides.
He said depressed patients who were getting better as a result
of medication might be more likely to tell doctors about a
suicide attempt, thereby muddying the data.
While Fergusson agreed that better trials are needed, he said
he was confident about the results of this analysis, because
it relied on placebo-controlled trials -- considered the most
definitive. And not all the patients getting drugs were being
treated for depression, he said -- there was evidence of increased
risk of suicide attempts for patients with all kinds of disorders.
Suicide "is uncommon but serious," Fergusson said in an interview.
"The biggest concern is these drugs are widely prescribed.
There are millions of people on the drugs, so even a risk
of one in a 1,000 when you amplify it to the millions, it
becomes a public health issue."
