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FDA Public Health Advisory
FDA Public Health Advisory
March 22, 2004
Subject: WORSENING DEPRESSION AND SUICIDALITY IN PATIENTS BEING
TREATED WITH ANTIDEPRESSANT MEDICATIONS
Today 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.
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Date created: March 22, 2004 |
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