March 22, 2004
Subject: WORSENING DEPRESSION AND SUICIDALITY IN PATIENTS BEING TREATED WITH ANTIDEPRESSANT MEDICATIONSToday the Food and Drug Administration (FDA) asked manufacturers of the following antidepressant drugs to include in their labeling a Warning statement that recommends close observation of adult and pediatric patients treated with these agents for worsening depression or the emergence of suicidality. The drugs that are the focus of this new Warning are: Prozac (fluoxetine); Zoloft (sertraline); Paxil (paroxetine); Luvox (fluvoxamine); Celexa (citalopram); Lexapro (escitalopram); Wellbutrin (bupropion); Effexor (venlafaxine); Serzone (nefazodone); and Remeron (mirtazapine).
Warning Information
- Health care providers
should carefully monitor patients receiving antidepressants for possible
worsening of depression or suicidality, especially at the beginning
of therapy or when the dose either increases or decreases. Although
FDA has not concluded that these drugs cause worsening depression
or suicidality, health care providers should be aware that worsening
of symptoms could be due to the underlying disease or might be a result
of drug therapy.
- Heath care providers
should carefully evaluate patients in whom depression persistently
worsens, or emergent suicidality is severe, abrupt in onset, or was
not part of the presenting symptoms, to determine what intervention,
including discontinuing or modifying the current drug therapy, is
indicated.
- Anxiety, agitation,
panic attacks, insomnia, irritability, hostility, impulsivity, akathisia
(severe restlessness), hypomania, and mania have been reported in
adult and pediatric patients being treated with antidepressants for
major depressive disorder as well as for other indications, both psychiatric
and nonpsychiatric. Although FDA has not concluded that these symptoms
are a precursor to either worsening of depression or the emergence
of suicidal impulses, there is concern that patients who experience
one or more of these symptoms may be at increased risk for worsening
depression or suicidality. Therefore, therapy should be evaluated,
and medications may need to be discontinued, when symptoms are severe,
abrupt in onset, or were not part of the patient’s presenting
symptoms.
- If a decision
is made to discontinue treatment, certain of these medications should
be tapered rather than stopped abruptly (see labeling for individual
drug products for details).
- Because antidepressants
are believed to have the potential for inducing manic episodes in
patients with bipolar disorder, there is a concern about using antidepressants
alone in this population. Therefore, patients should be adequately
screened to determine if they are at risk for bipolar disorder before
initiating antidepressant treatment so that they can be appropriately
monitored during treatment. Such screening should include a detailed
psychiatric history, including a family history of suicide, bipolar
disorder, and depression.
- Health care
providers should instruct patients, their families and their caregivers
to be alert for the emergence of agitation, irritability, and the
other symptoms described above, as well as the emergence of suicidality
and worsening depression, and to report such symptoms immediately
to their health care provider.
Background
Among antidepressants, only Prozac (fluoxetine) is approved for the treatment of pediatric major depressive disorder. Prozac (fluoxetine), Zoloft (sertraline), and Luvox (fluvoxamine) are approved for pediatric obsessive compulsive disorder. None of these drugs is approved as monotherapy for use in treating bipolar depression, either in adults or children.
The requested labeling changes are consistent with recommendations made to the Agency at a meeting of the Psychopharmacological Drugs Advisory Committee (PDAC) and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee (Peds AC), held on February 2, 2004. The possibility of suicidality associated with the use of antidepressant drug products in the pediatric population was also the subject of two previous FDA communications (FDA Talk Paper on June 19, 2003, and FDA Public Health Advisory on October 27, 2003).
FDA is continuing to review available clinical trial data for pediatric patients with depression and other psychiatric disorders to try to determine whether there is evidence that some or all antidepressants increase the risk of suicidality. Later this summer, the FDA plans to update the PDAC and Peds AC about the results of this review.
FDA plans to work closely with each of the nine manufacturers of the antidepressants that are the subject of today’s request to continue investigating how to optimize the safe use of these drugs and implement the proposed labeling changes and other safety communications in a timely manner.
Source: http://www.fda.gov/cder/drug/antidepressants/AntidepressanstPHA.htm
