FDA PUBLIC HEALTH ADVISORY

October 27, 2003
http://www.fda.gov/cder/drug/advisory/mdd.htm

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 ****ysis, 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 mentioned above.

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

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).