Benzodiazepines

0 Comments | Family Practice News, Dec 15, 2000 | by Lee Cohen

The use of benzodiazepines to treat anxiety and insomnia during pregnancy as well as pregnancy associated nausea, has persisted despite concerns dating back to the early 1970s that first-trimester use may increase the risk of cleft lip and/or cleft palate (oral clefts). But subsequent studies did not link major congenital malformations with benzodiazepines as a class of drugs.

Although this issue has largely been put to rest, there have been lingering concerns about first-trimester benzodiazepine exposure.

Two recent metaanalyses suggested that as a class, benzodiazepines such as lorazepam (Ativan), alprazolam (Xanax), diazepam (Valium), and clonazepam (Klonopin) may increase the risk of oral clefts with first-trimester exposure, but probably by no more than 0.6% (Am. J. Psychiatry 153[5]:592-606, 1996, and BMJ 317[7162]:839-43, 1998).

At our center, we do not consider benzodiazepines as absolutely contraindicated during pregnancy particularly for treating anxiety disorders.

Untreated anxiety during pregnancy may be associated with compromised perinatal outcomes such as preterm labor and lower Apgar scores, perhaps secondary to the direct effect of untreated anxiety on the fetal-placental unit. It has been hypothesized that this may involve fetal-placental insufficiency or uteroplacental insufficiency

There have been anecdotal reports of benzodiazepine discontinuation syndromes in children born to mothers treated with high doses of benzodiazepines during pregnancy; there also has been a case report of a mother treated with high doses of clonazepam whose baby had neonatal apnea.

But the incidence of associated neonatal complications is probably extremely small. In a study of 38 pregnant women with histories of panic disorder who were treated with 0.5-3.5 mg of clonazepam during pregnancy we found no evidence of neonatal toxicity or withdrawal syndromes in their babies (Psychother. Psychosom. In press).

The low incidence of perinatal complications suggests that abrupt discontinuation, particularly around delivery is contraindicated.

We do not arbitrarily discontinue benzodiazepines during pregnancy or during the peripartum period, although physicians often do so. Typically benzodiazepines are discontinued during pregnancy because of concerns over oral clefts or perinatal toxicity.

Discontinuation of antipanic drugs during pregnancy appears to be associated with a high risk of relapse, which may lead to compromised perinatal outcome. Several years ago, for example, we reported on a case of abruptio placentae associated with increases in blood pressure in a pregnant woman with untreated panic attacks.

And discontinuing treatment right before delivery increases a woman's risk of worsening anxiety disorders.

A few reports suggested that older children (followed through age 5) whose mothers used benzodiazepines during pregnancy had some developmental delays, but maternal substance abuse was a confounding factor. There are no other long-term behavioral data on the sequelae of benzodiazepine use during pregnancy.

Benzodiazepines are secreted into breast milk, but the nursing infant's exposure is usually small and does not justify counseling a woman who is on a benzodiazepine to defer breast-feeding. This is consistent with the American Academy of Pediatrics 2000 guidelines, which also advise against deferring treatment with benzodiazepines in this setting. We have reported on the safety of benzodiazepines during lactation.

For references on this topic, see the Massachusetts General Hospital Web site, www.mgh.harvard.edu/depts/womens/index.htm.> DR. LEE COHEN is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston.

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