FDA PUBLIC HEALTH
October 27, 2003
Subject: REPORTS OF SUICIDALITY IN
PEDIATRIC PATIENTS BEING TREATED WITH ANTIDEPRESSANT MEDICATIONS FOR
MAJOR DEPRESSIVE DISORDER (MDD)
Dear Health Care Professional:
The Food and Drug Administration (FDA)
would like to call your attention to reports of the occurrence of
suicidality (both suicidal ideation and suicide attempts) in
clinical trials for various antidepressant drugs in pediatric
patients with major depressive disorder (MDD). While
occurrences of suicidality are not unexpected in patients with MDD,
preliminary data suggest an excess of such reports for patients
assigned to several of these antidepressant drugs compared to those
assigned to placebo. FDA has completed a preliminary review of
such reports for 8 antidepressant drugs (citalopram, fluoxetine,
fluvoxamine*, mirtazapine, nefazodone, paroxetine, sertraline, and
venlafaxine) studied under the pediatric exclusivity provision, and
has determined that additional data and analysis, and also a public
discussion of available data, are needed. FDA plans to hold an
advisory committee meeting before the Psychopharmacologic Drugs
Advisory Committee and the Pediatric Subcommittee of the
Anti-Infective Drugs Advisory Committee on February 2, 2004.
You may also be aware of press and medical
journal reports of suicide attempts and completed suicides in
pediatric patients receiving antidepressants. Such reports are
very difficult to interpret, in the absence of a control group, as
these events also occur in untreated patients with depression.
Data available to FDA on these spontaneous reports will also be
presented at the February 2, 2004, advisory committee meeting
Pending the broad public discussion of
these issues, FDA wishes to emphasize several critical points.
In the 20 placebo-controlled trials being
considered for these 8 drugs, involving over 4100 pediatric
patients, there have been no reports of completed suicides.
However, FDA has not at this point been able to rule out an
increased risk of suicidality for any of these drugs, including
Paxil (paroxetine), which was the subject of a FDA Talk Paper on
June 19, 2003.
FDA emphasizes that, for the 7 drugs evaluated in
pediatric major depressive disorder (MDD), data reviewed by FDA were
adequate to establish effectiveness in MDD for only one of these
drugs, Prozac (fluoxetine). Failure to show effectiveness in
any particular study in pediatric MDD, however, is not definitive
evidence that the drug is not effective since trials may fail for
many reasons. FDA recognizes that pediatric MDD is a serious
condition for which there are few established treatment options, and
that clinicians often must make choices among treatments available
for adult MDD.
FDA emphasizes that these drugs must be used
with caution. Prescribers are reminded of the following
statement present in all antidepressant labeling:
“Suicide: The possibility of a suicide
attempt is inherent in major depressive disorder and may persist
until significant remission occurs. Close supervision of high-risk
patients should accompany initial drug therapy. Prescriptions for
Drug X should be written for the smallest quantity of tablets
consistent with good patient management, in order to reduce the risk
As recommended in the June 19, 2003 Talk Paper
for Paxil, FDA advises that caretakers of pediatric patients
receiving treatment with Paxil, or with any of the antidepressants,
talk to their doctor regarding the use of the drug.
Patients should not discontinue use of any of these drugs without
first consulting with their physicians, and, for certain of these
drugs, it is important that they not be abruptly discontinued (see
labeling for individual drugs).
*Although fluvoxamine data was reviewed with the
other antidepressant drugs data, it should be noted that it is not
approved as an antidepressant in the United States.
Additional Information (FDA
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Date created: October 27, 2003