Previous FDA Alert: Suicidality in Pediatric and Adult
Patients [Issued 6/2005]
7/2006: The issues described
below have been
addressed in product labeling.
All patients being treated with any type of antidepressants
should be observed closely for clinical worsening and
suicidality especially during the first few months of therapy
and when the dose is modified.
Pediatrics
FDA has concluded that suicidal thinking or behavior may
increase in pediatric patients treated with any type of
antidepressant, especially early in treatment. Increases in
suicidal thinking or behavior due to drug can be expected in
about 1 out of 50 treated pediatric patients. Note that,
although Cymbalta is prescribed for pediatric patients, it is
not approved by FDA for use in pediatric patients.
Adults
Several recent scientific publications report the possibility
of an increased risk for suicidal behavior in adults who are
being treated with antidepressant medications. Even before
these reports became available, FDA began a complete review of
all available data to determine whether there is an increased
risk of suicidality (suicidal thinking or behavior) in adults
being treated with any type of antidepressant medication. It is
expected that this review will require a year or longer to
complete. In the meantime, FDA is highlighting that adults
being treated with any type of antidepressant medication,
particularly those being treated for depression, should be
watched closely for worsening of depression and for increased
suicidal thinking or behavior.
A higher than expected rate of suicide attempts was observed in
the open-label extensions of controlled studies of Cymbalta for
stress urinary incontinence (SUI) in adult women. An increased
rate of suicidality was not seen in controlled trials of
Cymbalta for treatment of depression or diabetic neuropathic
pain (the approved indications for Cymbalta). Cymbalta is not
approved for the treatment of SUI. The FDA is evaluating
additional data to determine the relationship, if any, between
suicidality and Cymbalta use.
This information reflects FDA’s preliminary analysis of data
concerning this drug. FDA is considering, but has not reached a
final conclusion about, this information. FDA intends to update
this sheet when additional information or analyses become
available.
Recommendations
All patients being treated with any type of antidepressant for
any indication should be observed closely for clinical
worsening, suicidality, and unusual changes in behavior,
especially during the initial few months of a course of drug
therapy, or at times of dose changes, either increases or
decreases. For pediatric patients, such observation would
generally include at least weekly face-to-face contact with
patients or their family members or caregivers during the first
4 weeks of treatment, then every other week visits for the next
4 weeks, then at 12 weeks, and as clinically indicated beyond
12 weeks. Additional contact by telephone may be appropriate
between face-to-face visits. Adults whose symptoms worsen while
being treated with antidepressant medications, including an
increase in suicidal thinking or behavior, should be evaluated
by their healthcare professional.
Consideration should be given to changing the therapeutic
regimen, including possibly discontinuing the medication, in
patients whose depression is persistently worse, or who are
experiencing emergent suicidality or symptoms that might be
precursors to worsening depression or suicidality, especially
if these symptoms are severe, abrupt in onset, or were not part
of the patient’s presenting symptoms.
Physicians who are considering prescribing Cymbalta for SUI
should consider the following:
• Cymbalta is not approved for the treatment of SUI.
• In the open-label extensions of controlled studies of women
with SUI, a higher than expected rate of suicide attempts was
observed. A causal relationship with Cymbalta has not been
established.
Cymbalta is approved for the treatment of major depressive
disorder and diabetic neuropathic pain.
Data Summary
Pooled analyses of short-term (4 to 16 weeks)
placebo-controlled trials of 9 antidepressant drugs (SSRIs and
others) in children and adolescents with MDD, obsessive
compulsive disorder (OCD), or other psychiatric disorders (a
total of 24 trials involving over 4400 patients) have revealed
a greater risk of adverse events representing suicidal thinking
or behavior (suicidality) during the first few months of
treatment in those receiving antidepressants. The average risk
of such events in patients receiving antidepressants was 4
percent, twice the placebo risk of 2 percent. No suicides
occurred in these trials; however, the duration of treatment
was limited. Spontaneous post-marketing reports of
suicide-related events associated with the use of SSRIs,
including suicidal ideation, suicide attempt, self-mutilation
and completed suicide have been received. Because these events
may also be related to underlying psychiatric illness,
definitive evaluation of the effects of SSRIs on suicide
related events from post-marketing reports alone is not
possible, and the data from controlled clinical trials is more
informative.
Although there are no similar comprehensive data linking the
use of antidepressant medications and an increased risk of
suicidality in adults, FDA has initiated a complete review of
all available data. FDA has asked the manufacturers of all
marketed antidepressants to identify all placebo-controlled
clinical trials conducted in adults in their development
programs for their antidepressant products, regardless of the
indication studied, and to provide information from these
trials to FDA. Manufacturers are being asked to use a similar
approach to assembling this information as was used in
evaluating the risk of suicidality in placebo-controlled trials
in pediatric patients treated with antidepressant medications.
As of June, 2005, in trials of Cymbalta for the treatment of
SUI in women who were mostly middle-aged, eleven suicide
attempts and three cases of suicidal ideation were reported.
The reports of suicide attempt were all from the open label
extensions of these placebo-controlled trials (i.e., when all
patients were taking Cymbalta). The reports of suicidal
ideation occurred both during the placebo-controlled and open
label phases of the trials. There was no difference between
drug and placebo in the rate of suicidal ideation.
The role of confounding psychosocial stressors
or concomitant depression in the cases observed is not clear.
The suicide attempt rate in the SUI study population (based on
9,400 patients) was calculated to be 400 per 100,000 person
years. This rate is greater than the suicide attempt rate among
middle-aged U.S. women that has been reported in published
studies, i.e., 150 to 160 per 100,000 person years.
In addition, one death from suicide was reported in a Cymbalta
clinical pharmacology study in a healthy female volunteer
without SUI. No increase in suicidality was reported in
controlled trials of Cymbalta for depression or diabetic
neuropathic pain.
This information reflects FDA’s preliminary analysis of data
concerning this drug. FDA is considering, but has not reached a
final conclusion about, this information. FDA intends to update this
sheet when additional information or analyses become available.