Benefits and risks of psychiatric medications during pregnancy. (Practical Therapeutics).

Publication: American Family Physician

Publication Date: 15-AUG-02

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COPYRIGHT 2002 American Academy of Family Physicians

Psychiatric disorders are common in women of reproductive age. (1) Despite the morbidity associated with these disorders, there has been a tendency to avoid prescribing psychiatric medications during pregnancy. An expanding body of knowledge about the risks and benefits of these medications has made it possible to make more rational decisions about their use. (2,3) Growing evidence suggests that many of these agents are safe; however, there are some that clearly should be avoided.

This article reviews the risks and benefits of commonly used psychiatric medications. The use of these medications in lactation is the subject of a recent American Family Physician review. (4)

Risks of Psychiatric Medications

Psychiatric symptoms can affect pregnancy because of their effect on the mother's emotional state, functional status, ability to obtain proper prenatal care, and potential to engage in dangerous behavior. (2) After the birth of a child, untreated maternal mental illness may have an effect on the infant's development and well-being. (2,3,5)

All currently available psychopharmacologic agents and their metabolites cross the placenta, principally by simple diffusion. (6) The specific fetal serum levels are unknown, but they may be higher than maternal levels. (6) Medications can potentially affect the fetus in several ways: structural teratogenesis (birth defects), behavioral teratogenesis, and perinatal syndromes. (2,6)

STRUCTURAL TERATOGENESIS

The timing of exposure to chemical agents during development affects the risk for malformations. (7) The second through the eighth weeks postfertilization, during which time the development of major organ systems occurs, is the critical period of risk for structural teratogenesis. (7)

BEHAVIORAL TERATOGENESIS

Behavioral teratogenicity is the occurrence of behavior or neuropsychiatric symptoms in offspring after in utero exposure to a drug or toxin. (3) Subsequent prospective human studies have not shown convincing evidence for such an effect, perhaps because of the difficulty of separating the behavioral teratogenicity of maternal mental illness from drug effects. (3,5)

PERINATAL SYNDROMES

Administration of psychiatric medications proximate to delivery can cause what are termed perinatal syndromes (Table 1) (3,8-10) of drug intoxication or withdrawal. In some cases, these effects are reasonably well established and pharmacologically plausible, such as the somnolence and hypotonia of infants exposed to intrapartum benzodiazepines. (2) In most cases, the evidence is limited to case reports in which nonspecific neonatal effects (e.g., poor feeding and irritability) have been interpreted as possible evidence of exposure to, or withdrawal from, certain antidepressants. (8) The limited data are best viewed as potential class effects, and it is not possible to draw conclusions about specific agents within classes.

FDA Risk Categories

Table 2 (11) shows the five U.S. Food and Drug Administration (FDA) categories for drug use in pregnancy. These ratings have a number of limitations, including a lack of internal consistency within classes of medications; attempts to aggregate diverse information, such as risks, into a single rating; poor discrimination between different medications within a class; and lack of agreement with the findings of other credible sources. While physicians should be familiar with these ratings, they are likely to find a variety of online and print resources to be more useful. (7,12-16)

Risks of Specific Agents

ANTIDEPRESSANTS

The results of numerous studies that included thousands of pooled patients taking tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) support the relative safety of these medications for use throughout pregnancy. (8,17,18) Neither the TCAs nor fluoxetine has been associated with major teratogenic effects. (8,17,18) In...

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