The U.S. Food and Drug Administration (FDA) has reminded prescribers and
patients alike that adults who take antidepressant medications should be
watched closely for worsening of depression and the possibility of suicidal
thoughts and behaviors, especially early in treatment or when dosing is either
increased or decreased.
In addition, the agency said in a Public Health Advisory issued June 30,
adults whose symptoms worsen while taking antidepressant medications should be
promptly evaluated by their health care professional. The recommendations, the
FDA said, "are consistent with existing warnings for treated adults in
the approved labeling (package insert) for antidepressant
The advisory and an accompanying FDA Talk Paper were issued as an interim
step while the agency awaits results of an in-depth analysis of large amounts
of clinical-trials data on antidepressant use in adults. That analysis will
mirror the full review of child and adolescent data completed last year by
suicide experts at Columbia University (Psychiatric News, March 19,
2004; March 5, 2004).
At press time the FDA was unable to confirm whether the same Columbia
researchers would play a part in the adult-data analysis.
The FDA said that rather than going another year without clear advice for
adults taking antidepressants, it was prompted to issue the advisory by the
publication of two research articles earlier this year that "suggested
the possibility of an increased risk for suicidal behavior in adults who are
being treated with antidepressant medications" (see article at
Last fall, prior to the agency's becoming aware of the adult analyses,
which were subsequently published in February, the agency announced that it
would undertake a full reclassification of all adverse-event data from
clinical trials involving antidepressant use in adults.
Last year researchers at Columbia reviewed all available adverse-event data
from clinical trials involving antidepressants in children and adolescents.
The experts reclassified each of the adverse-event reports to determine
whether it represented a true suicidal/self-harming event.
Based on the reclassified adverse-event data, an FDA internal analysis last
summer found that there was about a twofold increase in the occurrence of
suicidal thoughts or behaviors in children and adolescents taking
antidepressants in clinical trials compared with subjects taking placebo.
However, the FDA also found that there was no difference in the emergence of
suicidality or in worsening of existing suicidality between the two groups of
clinical-trial participants. The FDA has acknowledged the apparent
contradiction in the findings but to date has not offered any explanation.
The results of that analysis prompted the FDA to require black-box warnings
on labels of all antidepressants marketed in the United States
(Psychiatric News, November 5, 2004).
Earlier this year, the FDA asked the manufacturers of all marketed
antidepressants to "fully evaluate the risk of suicidality in adults
treated with these drugs," the public health advisory explained.
Manufacturers were asked to identify all placebo-controlled trials conducted
in adults for any antidepressant product, regardless of whether the trial was
specifically evaluating the use of the drug for depression. Trials
investigating the use of the drugs for anxiety disorders, personality
disorders, eating disorders, chronic pain, diabetic neuropathy, stress urinary
incontinence, and any other indication will be included in the new adult
Manufacturers were asked for detailed information on all adverse events
recorded in all trials, following the same format as that used in collecting
the child and adolescent data last year. It was important, the agency noted,
to include all available data, regardless of the indication, because some
drugs have been associated with an increased risk of suicidal thoughts and
behaviors in trials for one indication, but not others (see box above).
The FDA said its "comprehensive review will involve many hundreds of
individual clinical trials and many thousands of adult patients." The
analysis will take "a year or more to complete" because of the
large number of trials and thousands of adverse-event records that must be
"FDA will make the results of its review available to the public once
its analyses are complete and will update this advisory in the meantime if
more definitive information becomes available," the advisory stated.
"FDA Public Health Advisory: Suicidality in Adults Being
Treated With Antidepressant Medications" is posted at<www.fda.gov/cder/drug/advisory/SSRI200507.htm>.
More information about the analysis of child and adolescent data is posted at<www.fda.gov/cder/drug/antidepressants/default.htm>.▪