|
|
TABLE 5
Treatment and Prevention of Panic Disorder During Pregnancy
|
|
| Drug Class |
Remarks
|
| Generic Name |
| Trade Name
|
|
Treatment and prevention: Benzodiazepine agonists
Alprazolam
Xanax
Clonazepam
Klonopin
Diazepam
Valium
Lorazepam
Ativan |
Neonatal effects: The
major neonatal side effects of benzodiazepines include sedation and
dependence with withdrawal signs. A benzodiazepine-induced "floppy
infant syndrome" characterized by muscular hypotonia, low Apgar
scores, hypothermia, impaired response to cold, and neurologic
depression can occur at the time of delivery in
benzodiazepine-dependent neonates, even with the lower doses used to
treat anxiety disorders. Withdrawal signs include hypertonia,
hyperreflexia, restlessness, irritability, seizures, abnormal sleep
patterns, inconsolable crying, tremors or jerking of the extremities,
bradycardia, cyanosis, chewing movements, and abdominal distention.
These signs can appear shortly after delivery to 3 weeks after birth
and last up to several months depending on the degree of dependence and
the pharmacokinetic profile of the benzodiazepine. Diazepam has a
long-acting metabolite, dimethyldiazepam, whose mean elimination
half-life is 73 (30-100) hours in adults. Of the benzodiazepines with
no or weakly active, short-lived metabolites, clonazepam has the
longest mean elimination half-life of 23 (18-50) hours in adults.
|
Prevention only: selective serotonin reuptake
inhibitor
Fluoxetine
Prozac
Tricyclic
antidepresssant Imipramine
Janimine
|
Teratogenic effects: Tricyclics and fluoxetine do not have
known teratogenic effects in the human.5,7,22 Insufficient
human data exist to ascertain the teratogenicity of monamine oxidase
inhibitors. The belief that diazepan causes congenital malformations,
especially cleft lip/palate, is controversial.7 No
congenital defects in humans have been attributed to lorazepam or
alprazolam.79 The data based on the conclusion for
alprazolam have been contested,11 but the authors state
that the risk for oral cleft remains small. A limited surveillance
study revealed 3 major birth defects (0.8 expected) in 19 pregnant
women exposed to clonazepam80; therefore, targeted
sonography for anomaly screening is recommended at 18 to 20 weeks of
gestation. |
Tofranil
Monoamine oxidase
inhibitor
Phenelzine
Nardil |
Animal
studies have suggested that neurobehavioral teratogenicity occurs with
some of the benzodiazepines.81-84 In humans, the findings
were mixed, no motor or cognitive deficits were observed in children at
8 months of age, and no effects on IQ were observed at 4 years of
age.85 Conversely, delayed motor development and mental
retardation were reported in 7 of 8 children with in utero exposure to
various benzodiazepines.86
Guidelines: From the viewpoint of the fetus, fluoxetine
is recommended for preventive therapy for panic disorder during
pregnancy. When a benzodiazepine is indicated for treatment of an acute
panic disorder in the pregnant patient, alprazolam or lorazepam is
preferred during pregnancy to longer-acting diazepam and clonazepam. No
birth defects have been linked to alprazolam, lorazepam, or fluoxetine.
Lorazepam is preferred over alprazolam for preventive therapy, because
it has a somewhat longer duration of action, it lacks active
metabolites, and it does not seem to be associated with an immediate
and as severe a withdrawal syndrome in the neonate compared with
alprazolam. However, withdrawal reactions may be more severe but less
protracted compared with the longer acting benzodiazepines, clonazepam,
and diazepam. |
|
