Maternal Citalopram Treatment Prompts Adverse Event Reports

ST. PETE BEACH, FLA. — A total of 228 adverse events associated with the use of citalopram (Celexa) during pregnancy has been reported to the Food and Drug Administration's Adverse Event Reporting System since the drug was approved in 1998, J. Edward Fisher, Jr., Ph.D., reported at the annual meeting of the Teratology Society.

Of these reports, 120 involved adverse developmental events, and 38 of those events occurred during the peri- or postnatal period.

A total of 31 of the 38 cases occurred in the early neonatal period during the first week of life, and 18 of these involved neonatal withdrawal symptoms, including jitteriness, rigidity, tremor, and confusion associated with citalopram exposure in either the third trimester or throughout pregnancy.

The doses used by the pregnant women ranged from 20 to 40 mg/day, said Dr. Fisher, a pharmacologist with the FDA Center for Drug Evaluation and Research, Rockville, Md.

Reports of symptoms consistent with neonatal withdrawal syndrome and associated with maternal use of selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) prompted the FDA last year to require labeling changes warning of the risk associated with their use during pregnancy.

Possible cases of neonatal withdrawal syndrome have been reported with all SSRIs, but in at least one study, the majority of cases were associated with paroxetine.

In that study of 93 cases, 64 were associated with paroxetine, 14 with fluoxetine, 9 with sertraline, and 7 with citalopram, which is marketed as Celexa by Forest Laboratories. (One patient received both paroxetine and fluoxetine.) Another large study showed that the association between paroxetine and neonatal symptoms was no greater than that of other SSRIs.

The citalopram reports noted by Dr. Fisher and the other reports involving various SSRIs and SNRIs and their association with neonatal withdrawal symptoms suggest a class effect. But the data remain insufficient for determining whether there are significant differences among the individual drugs in this class, he told this newspaper.

As a rule, “the use of this agent has to be balanced with respect to the benefit to the mother if she is depressed. There is a general consensus that SSRIs and SNRIs are preferable to tricyclics in terms of safety and efficacy,” said Jeffrey Jonas, M.D., senior vice president of Forest Research Institute, a division of Forest Labs.

Experts continue to urge clinicians to weigh the risks and benefits of SSRI and SNRI use in pregnancy and to consider the increased risk of maternal morbidity associated with untreated maternal depression.