FDA ISSUES PUBLIC HEALTH ADVISORY ON CAUTIONS FOR USE OF ANTIDEPRESSANTS
IN ADULTS AND CHILDREN
The Food and Drug Administration today issued a Public Health Advisory that
provides further cautions to physicians, their patients, and families and
caregivers of patients about the need to closely monitor both adults and children
with depression, especially at the beginning of treatment, or when the doses
are changed with either an increase or decrease in the dose. FDA has been
closely reviewing the results of antidepressant studies in children, since
June 2003, after an initial report on studies with paroxetine (Paxil), and
subsequent reports on studies of other drugs, appeared to suggest an increased
risk of suicidal thoughts and actions in the children given antidepressants.
There were no suicides in any of the trials. On close examination of the initial
reports, it was unclear whether certain behaviors reported in these studies
represented actual suicide attempts, or other self-injurious behavior that
was not suicide-related. FDA has initiated a full review of these reported
behaviors by experts in such evaluation. However, it is not yet clear whether
antidepressants contribute to the emergence of suicidal thinking and behavior.
The agency is advising clinicians, patients, families and caregivers of adults
and children that they should closely monitor all patients being placed on
therapy with these drugs for worsening depression and suicidal thinking, which
can occur during the early period of treatment. The agency is also advising
that these patients be observed for certain behaviors that are known to be
associated with these drugs, such as anxiety, agitation, panic attacks, insomnia,
irritability, hostility, impulsivity, akathisia (severe restlessness), hypomania,
and mania, and that physicians be particularly vigilant in patients who may
have bipolar disorder. FDA is asking manufacturers to change the labels of
ten drugs to include stronger cautions and warnings about the need to monitor
patients for the worsening of depression and the emergence of suicidal ideation,
regardless of the cause of such worsening. The drugs under review include
bupropion, citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine,
sertraline, escitalopram and venlafaxine. It should be noted that the only
drug that has received approval for use in children with major depressive
disorder is fluoxetine (Prozac). Several of these drugs are approved for the
treatment of obsessive-compulsive disorder in pediatric patients, i.e., sertraline
(Zoloft), fluoxetine (Prozac), and fluvoxamine (Luvox). Luvox is not approved
as an antidepressant in the United States. These interim actions follow recommendations
made by FDA's Psychopharmacologic Drugs and Pediatric Subcommittee of the
Anti-Infective Drugs Advisory Committees, which met on February 2, 2004. The
advisory committee members advised FDA that the labeling should draw more
attention to the need to monitor patients being treated with certain antidepressants.
FDA has previously noted (in Public Health Advisory and a Talk Paper T03-70
published Oct. 27, 2003) the possible finding of increased suicidal thinking
or behavior, but emphasized that it was not clear that the drugs caused such
events and additional analyses were being done to allow FDA to seek more definitive
answers. The Public Health Advisory containing the new label warnings and
cautions is available online at <http://www.fda.gov/cder/drug/antidepressants/default.htm>.
Later this summer, FDA plans to update the Advisory Committees on the results
of the expert analyses and its own analyses of the pediatric suicidality data.
