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Information for Healthcare Professionals
Escitalopram (marketed as Lexapro)
Selective Serotonin Reuptake Inhibitors (SSRIs)
FDA ALERT [7/2006]: Increased Risk of Neonatal
Persistent Pulmonary Hypertension
A recently
published case-control study has shown that infants
born to mothers who took selective serotonin
reuptake inhibitors (SSRIs) after the 20th week of
pregnancy were 6 times more likely to have
persistent pulmonary hypertension (PPHN) than
infants born to mothers who did not take
antidepressants during pregnancy (see SSRI drug
names at the bottom of this sheet). The background
risk of a woman giving birth to an infant affected
by PPHN in the general population is estimated to be
about 1 to 2 infants per 1000 live births. Neonatal
PPHN is associated with significant morbidity and
mortality. The FDA is updating the prescribing
information for all SSRIs with this new information.
The FDA is also accruing data from additional
sources pertaining to the potential association
between SSRIs and neonatal PPHN. The FDA will
provide additional information when it becomes
available. In the interim, the FDA recommends that
physicians carefully consider and discuss with
patients the potential risks and benefits of SSRI
treatment throughout pregnancy, including late
pregnancy.
This information reflects FDA’s current analysis of
data available to FDA concerning these drugs. FDA
intends to update this sheet when additional
information or analyses become available.
To report any
unexpected adverse or serious events associated with
the use of this drug, please contact the FDA
MedWatch program at 1-800-FDA-1088 or
http://www.fda.gov/medwatch/report/hcp.htm
Considerations
Physicians should consider the benefits and risks of
treating pregnant women with SSRIs, alternative
treatments, or no treatment late in pregnancy.
Data Summary
A retrospective case-control study published on
February 9, 2006, in the New England Journal of
Medicine assessed the risk for persistent pulmonary
hypertension of the newborn (PPHN) following
exposure to SSRIs during pregnancy. 377 women whose
infants were born with PPHN and 836 women whose
infants were healthy were enrolled in the study in
four United States metropolitan areas between 1998
and 2003. The study showed that infants born to
mothers who took SSRIs after the completion of the
20th week of gestation were 6 times more likely to
have PPHN than infants who were not exposed to
antidepressants during pregnancy. 14 infants with
PPHN and 6 healthy control infants had been exposed
to an SSRI after the 20th week of gestation. There
were too few cases of PPHN with each individual SSRI
to compare risks for PPHN with individual SSRIs. The
study did not find an association between exposure
to SSRIs during the first 20 weeks of gestation and
PPHN.
Exposure to non-SSRI antidepressants did not appear
to be associated with an increased risk of PPHN,
although the number of infants with exposure to
non-SSRI antidepressants was too small to permit a
reliable risk estimate or comparison with the risk
observed for SSRIs.
In weighing the risks and benefits of treatment with
SSRIs and other antidepressants during pregnancy for
individual patients, physicians should also note the
recent publication of a prospective longitudinal
study of 201 pregnant women with a history of major
depression in the February 1, 2006, issue of JAMA.
In this study, women who discontinued antidepressant
medication during pregnancy had a higher risk of
relapse of major depression during pregnancy (68%)
than women who maintained antidepressant medication
throughout pregnancy (26%).
SSRI Drug Names
Information for
Healthcare Professionals
Escitalopram (marketed as Lexapro)
Selective
Serotonin Reuptake Inhibitors (SSRIs)
Selective Serotonin-Norepinephrine Reuptake
Inhibitors (SNRIs)
5-Hydroxytryptamine Receptor Agonists (Triptans)
FDA ALERT
[7/2006]: Potentially Life-Threatening Serotonin
Syndrome with Combined Use of SSRIs or SNRIs and
Triptan Medications
There is the
potential for life-threatening serotonin syndrome (a
syndrome of changes in mental status, autonomic
instability, neuromuscular abnormalities, and
gastrointestinal symptoms) in patients taking
5-hydroxytryptamine receptor agonists (triptans) and
selective serotonin reuptake inhibitors (SSRIs) or
selective serotonin/norepinephrine reuptake
inhibitors (SNRIs) concomitantly (see drug names at
the bottom of this sheet). This information is based
on reports of serotonin syndrome occurring in
patients treated with triptans and SSRIs/SNRIs, and
the biological plausibility of such a reaction in
persons receiving two serotonergic medications. The
FDA recommends that patients treated concomitantly
with a triptan and an SSRI/SNRI be informed of the
possibility of serotonin syndrome (which may be more
likely to occur when starting or increasing the dose
of an SSRI, SNRI, or triptan) and be carefully
followed.
This
information reflects FDA’s current analysis of data
available to FDA concerning these drugs. FDA intends
to update this sheet when additional information or
analyses become available.
To report any
unexpected adverse or serious events associated with
the use of this drug, please contact the FDA
MedWatch program at 1-800-FDA-1088 or
http://www.fda.gov/medwatch/report/hcp.htm
Considerations
-
Weigh the potential risk of concomitant
SSRI/SNRI and triptan use with the benefit
expected from using each drug, prior to
prescribing these drugs together.
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When prescribing an SSRI or a triptan,
physicians should discuss the possibility of
serotonin syndrome with patients if an SSRI and
a triptan will be used concomitantly. Healthcare
providers should keep in mind that triptans are
often used intermittently, and that the SSRI,
SNRI, or triptan may be prescribed by a
different healthcare provider.
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Healthcare providers should be alert to the
highly variable signs and symptoms of serotonin
syndrome. Serotonin syndrome symptoms may
include mental status changes (e.g., agitation,
hallucinations, coma), autonomic instability
(e.g., tachycardia, labile blood pressure,
hyperthermia), neuromuscular aberrations (e.g.
hyperreflexia, incoordination) and/or
gastrointestinal symptoms (e.g., nausea,
vomiting, diarrhea).
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If concomitant treatment with an SSRI or SNRI
and triptan is clinically warranted, the patient
should be carefully observed, particularly
during treatment initiation and dose increases.
Data Summary
The FDA has reviewed 27 reports of serotonin
syndrome reported in association with concomitant
SSRI or SNRI and triptan use. Two reports described
life-threatening events and 13 reports stated that
the patients required hospitalization. Some of the
cases occurred in patients who had previously used
concomitant SSRIs or SNRIs and triptans without
experiencing serotonin syndrome. The reported signs
and symptoms of serotonin syndrome were highly
variable and included respiratory failure, coma,
mania, hallucinations, confusion, dizziness,
hyperthermia, hypertension, sweating, trembling,
weakness, and ataxia. In 8 cases, recent dose
increases or addition of another serotonergic drug
to an SSRI/triptan or SNRI/triptan combination were
temporally related to symptom onset. The median time
to onset subsequent to the addition of another
serotonergic drug or dose increase of a serotonergic
drug was 1 day, with a range of 10 minutes to 6
days.
Serotonin syndrome following concomitant SSRI or
SNRI and triptan use is biologically plausible.
SSRIs, SNRIs, and triptans independently increase
serotonin levels. Therefore, it is expected that
concomitant use of SSRIs or SNRIs and triptans would
result in higher serotonin levels than the serotonin
levels observed with the use of SSRIs, SNRIs, or
triptans alone, potentially leading to serotonin
syndrome.
SSRIs and a
Combination
Drug Containing an SSRI
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SNRIs
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Triptans
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Cymbalta (duloxetine)
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Effexor (venlafaxine)
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Additional
Information
http://www.fda.gov/cder/drug/antidepressants/default.htm
Report serious
adverse events to
FDA’s MedWatch reporting system by completing a form
on line at
http://www.fda.gov/medwatch/report.htm, by faxing
(1-800-FDA-0178),
by mail using the postage-paid address form provided
online
(5600 Fishers Lane, Rockville, MD 20852-9787),
or by telephone (1-800-FDA-1088
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