Psychopharmakologie
Online Coverage from the 9th Annual U.S Psychiatric & Mental Health
Congress
© 1996 Medscape, Inc.
Treating Pregnant Patients with Psychotropic Drugs
Speaker: Laura Miller, M.D.
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Contents
Background
When considering pharmacotherapeutic options in pregnancy, the range of
possible risks is vast. However, these risks must be weighed against the risks
of not using pharmacotherapy, said Dr. Laura Miller, Assistant Professor of
Psychiatry at the University of Illinois, in her presentation on pharmacotherapy
in pregnancy. "It is crucial" she said "to try and help these women to manage
their illness in a way that will allow them to function as parents, without
causing excessive risk to the fetus."
According to Dr. Miller, the possible risks associated with some psychoactive
drugs are an increase in the rates of spontaneous abortion, prematurity, as well
as an increase or decrease in fertility. Some drugs are also associated with
morphological teratogenicity, and, theoretically, with behavioral teratogenicity
by affecting developing neurotransmitters. These drugs may also cause side
effects or symptoms of withdrawal in the fetus or neonate, as well as in the
mother. These potential effects and side effects must be strongly considered not
just with the pregnant patient, but with all patients of child-bearing
potential.
Quantifying the risks of various psychopharmacologic agents, Dr. Miller
stated, is fraught with difficulty. Most of the information available is for
older medications and these studies are frequently flawed by the inclusion of
confounding variables such as: other medications taken, nutritional status of
the mother, physical and emotional stresses during pregnancy, maternal age, and
environmental toxins to name just a few.
Non-pharmacological options should, of course, be fully explored first for
all psychiatric problems arising in pregnant or potentially pregnant women.
However, cultural attitudes toward pregnancy have historically resulted in a
tendency to under treat pharmacologically and to allow women to remain highly
symptomatic throughout their pregnancy. Dr. Miller clearly illustrated this is
often not in the best interest of either the mother or the fetus.
Major Depression
In cases of major depression, the risks of untreated illness may be extensive
and include: maternal and fetal malnutrition, poor prenatal care, compromised
maternal-fetal relationship, and neonatal irritability.
To date, the most widely studied antidepressants have been the tricyclics,
although in recent years there have been a few early studies of fluoxetine in
pregnancy . According to Dr. Miller, in the aggregate there has been no
documented increase in the rate of congenital abnormalities associated with the
use of tricyclics during pregnancy and Dr. Miller recommended using either
desipramine or nortriptyline if no other contraindications exist. While several
studies of fluoxetine showed no increased risks either, a recent study in the
New England Journal of Medicine suggested the possibility of an increase in
multiple minor anomalies and premature delivery.
When a clinician decides to prescribe an antidepressant, in particular a
tricyclic, Dr. Miller recommended the following precautions: check serum levels
frequently, as a woman's total body water and plasma volume expand during
pregnancy, and doses may require frequent adjustment; and taper the medication
starting 3 weeks prior to the EDC to minimize neonatal withdrawal symptoms.
Prophylactic treatment should be resumed after delivery due to the increased
risks of post-partum depression in these women.
Acute Mania
The psychopharmacological treatment of pregnant women with acute mania is
somewhat more problematic, but again, the risks of untreated illness are great.
Manic women tend to be impulsive and hypersexual, increasing their risk of
acquiring and transmitting HIV. They may also refuse prenatal care and be unable
to cope with pregnancy complications such as gestational diabetes or forced bed
rest.
It is now believed that the original studies citing the risks of cardiac
malformations with lithium during pregnancy were overstated and that lithium is
at worst "a weak cardiovascular teratogen during the 4th to 10th weeks of
gestation." Other potential risks of lithium include a transient neonatal
hypothyroidism and fetal nephrogenic diabetes insipidus. The latter poses no
danger to the fetus, however, the resulting polyhydramnios can cause maternal
respiratory compromise and is an indication to stop treatment. If lithium is to
be administered during pregnancy, it is best to begin treatment after the 10th
week of gestation. Serum levels should be frequently monitored and maintained at
the lowest therapeutic level possible and the drug should be given in small
divided doses to avoid toxic peak serum levels. As Dr. Miller stressed, the dose
must be reduced by 50% at time of labor, otherwise the fluid mobilization will
cause maternal and fetal toxicity. In addition, women should be warned that in
animal studies, ethanol and lithium in combination have been shown to potentiate
the toxic effects of each.
While anticonvulsants remain alternatives to lithium in the treatment of
mania in pregnancy, both carbamazepine and valproic acid have been shown to
increase the risks of neural tube defects and to increase the degradation of
certain vitamins. With the use of these drugs, Dr. Miller recommended minimizing
the risks to the fetus by avoidance of the drug during the first trimester when
possible, and folate supplementation before and during pregnancy. Alpha fetal
protein (AFP) screening can be used to detect neural tube defects., however, AFP
is associated with many false negatives, and a more definitive test, such as
amniocentesis, may be preferable. If the mother is taking carbamazepine, she
should begin vitamin K supplementation during the last months of pregnancy and
the newborn should receive one intramuscular injection of vitamin K at birth.
Electroconvulsive therapy (ECT), especially during the first trimester, is an
excellent alternative to pharmacotherapy for the treatment of either depression
or mania. Though few cases of transient fetal tachycardia have been reported no
long term sequelae have been shown. As long as the appropriate modifications in
technique are made, the procedure is considered safe both for mother and fetus.
Psychosis
Dr. Miller noted that untreated maternal psychosis poses some of the greatest
risks to the fetus throughout the pregnancy. Paranoia may lead to malnutrition
and poor prenatal care. Women may attempt premature self-delivery, or most
devastating of all, neonaticide which occurs in 800-1000 cases per year.
Of the older antipsychotics, only the phenothiazines have been associated
with an increase in teratogenicity. Treatment with high potency agents -- the
best studied are haloperidol and trifluoperazine -- is recommended at the lowest
effective doses. One long term effect of treatment with these agents is that
school age children are both taller and heavier than their peers, but no
cognitive impairments have been seen.
As many women being treated with antipsychotics develop extrapyramidal
symptoms (EPS), consideration must be given to the agents used to treat the side
effects as well. Generally speaking, pregnant women on neuroleptics should be
given calcium supplementation, which has been shown to reduce EPS, but no other
prophylaxis is indicated. If symptoms develop, it is important to note that both
benztropine and diphenhydramine have been associated with an increased risk of
minor malformations. By far the safest drug to use is propranolol which is
excellent for restlessness but does not always treat other symptoms as
effectively.
Anxiety
Mild to moderate levels of anxiety can often be treated successfully with
non-pharmacological interventions. Severe, persistent anxiety, however, should
be treated because it can increase prematurity, prolong labor, and may have long
term behavioral effects on the fetus and neonate.
Diazepam has been weakly linked to an increased incidence of cleft palate. If
benzodiazepines must be used, lorazepam or clonazepam are recommended as they
are well studied and have not been shown to accumulate in the fetus to the same
degree as diazepam. With higher doses, the risks of toxicity or withdrawal at
birth are significant and use of these agents around the time of delivery may,
theoretically, increase the incidence of kernicterus.
Dr. Miller briefly discussed drugs used to treat addiction, such as
disulfiram or methadone. Disulfiram is contraindicated in pregnancy because of
resulting hypotension and poor placental perfusion. Methadone, however, is not
contraindicated. Even with its potential side effects, methadone has been shown
to result in better outcomes than allowing a woman to continue using street
heroin.
In summary, the decision of when and how to treat pregnant women with
psychotropic medications is a complicated one that involves a thorough and
thoughtful evaluation of the risks and benefits. In the long run, it is often in
the best interests of both mother and child to treat serious mental illness
pharmacologically, in spite of the risks, rather than prolong suffering and
further impair a possibly already tenuous maternal - child bond.
Suggested Readings
- Miller LJ. Psychopharmacology during pregnancy. Psychiatry Update
1996;3(3): 79-86.
- Miller LJ. Psychiatric medication during pregnancy: understanding and
minimizing risks. Psychiatric Annals 1994; 24(2): 69-75.
- Chambers CD; Johnson KA; Dick LM, et al. Birth outcomes in pregnant women
taking fluoxetine. N Engl J Med 1996;335:1010-5.
- Smith RM: Women with Bipolar Illness. Medscape Conference News Online,
1996 American Psychiatric Association Meeting.
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