Klinische Pharmakologie / Psychopharmakologie

 
 

 
 

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.

Back 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

  1. Miller LJ. Psychopharmacology during pregnancy. Psychiatry Update 1996;3(3): 79-86.
  2. Miller LJ. Psychiatric medication during pregnancy: understanding and minimizing risks. Psychiatric Annals 1994; 24(2): 69-75.
  3. Chambers CD; Johnson KA; Dick LM, et al. Birth outcomes in pregnant women taking fluoxetine. N Engl J Med 1996;335:1010-5.
  4. Smith RM: Women with Bipolar Illness. Medscape Conference News Online, 1996 American Psychiatric Association Meeting.

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