FDA Issues Public Health Advisory Entitled: Reports Of Suicidality in Pediatric Patients Being Treated with Antidepressant Medications for Major Depressive Disorder (MDD)The Food and Drug Administration (FDA) is issuing a Public Health Advisory to alert physicians to reports of suicidal thinking (and suicide attempts) in clinical studies of various antidepressant drugs in pediatric patients with major depressive disorder (MDD).
FDA recognizes that pediatric MDD is a serious condition for which there are few established treatment options. In addition to use of non-medication approaches to treatment, clinicians must often make choices among drug treatments available for adult MDD. Currently, Prozac (fluoxetine) is the only drug labeled for use in Pediatric MDD, and was approved recently under the Pediatric Exclusivity provision.
FDA has completed a preliminary review of reports for eight antidepressant drugs - citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, and venlafaxine - all studied under the pediatric exclusivity provision of the FDA Modernization Act (FDAMA, 1997). (Although fluvoxamine data were reviewed along with the other antidepressant drugs, it should be noted that it is not approved as an antidepressant in the United States.)
FDA notes, to date, that the data do not clearly establish an association between the use of these drugs and increased suicidal thoughts or actions by pediatric patients. Nevertheless, it is not possible at this point to rule out an increased risk of these adverse events for any of these drugs, including Paxil (paroxetine), which was the subject of a FDA Talk Paper on June 19, 2003. That talk paper advised that FDA is reviewing the safety concerns related to off-label use of Paxil in children based on recent trials of this drug.
FDA emphasizes that, for the seven drugs evaluated in pediatric major depressive disorder (MDD), data FDA reviewed were adequate to establish effectiveness in MDD only for Prozac (fluoxetine). Failure to show effectiveness in any particular study in pediatric MDD, however, is not definitive evidence that the drug is not effective because trials may fail for many reasons.
FDA is aware of press and medical journal reports of suicide attempts and completed suicides in pediatric patients receiving antidepressants, and many such reports have also been submitted to FDA as spontaneous reports. Such reports are very difficult to interpret, however, in the absence of a control group, as these events also occur in untreated patients with depression.
FDA emphasized the need for additional data, analyses and a public discussion of available data. As we recognize that this is a serious illness, we need a better understanding of how to use the products we have.
In order to promote a public discussion of data and pertinent regulatory actions, the FDA scheduled a meeting on February 2, 2004, before the Psychopharmacologic Drugs Advisory committee and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee.
The agency also reminds physicians and patients that these drugs must be used with caution, both in adults and children. The labeling of antidepressant drugs already carries precautionary language that the possibility of a suicide attempt is inherent in MDD and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy.
In its Public Health Advisory, FDA recommends that caretakers of pediatric patients receiving treatments with any of these antidepressants talk to their doctors before stopping the use of these drugs. 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.
FDA sent the advisory through its Medwatch partners, which includes doctors and organizations. FDA provides more information on the clinical study data in its Public Health Advisory, which is available on the FDA website at http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm096273.htm.
reproduced from FDA Talk Paper released on October 27, 2003