BUSPIRONE

Fetal Risk Summary

Buspirone is an antianxiety agent that is unrelated chemically and pharmacologically to other sedative and anxiolytic drugs. Reproduction studies in rats and rabbits at doses approximately 30 times the maximum recommended human dose revealed no fertility impairment or fetal adverse effects (1).

A 1993 report described the use of buspirone, in combination with four other agents, all started before conception, in a pregnant woman with major depression, a coexisting panic disorder, and migraine headaches (2). The pregnancy was electively terminated after 12 weeks, resulting in the delivery of a male fetus with normal organ formation and a normal placenta. No dysmorphology was observed during the complete macroscopic and microscopic examination, including a normal 46,XY karyotype.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 42 newborns had been exposed to buspirone during the 1st trimester (F. Rosa, personal communication, FDA, 1993). One (2.4%) major birth defect was observed (two expected). The anomaly was not included in six defect categories for which specific data were available (cardiovascular defects, oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias).

A 1998 non-interventional observational cohort study described the outcomes of pregnancies in women who had been prescribed one or more of 34 newly marketed drugs by general practitioners in England (3). Data were obtained by questionnaires sent to the prescribing physicians one month after the expected or possible date of delivery. In 831 (78%) of the pregnancies, a newly marketed drug was thought to have been taken during the 1st trimetster with birth defects noted in 14 (2.5%) singleton births of the 557 newborns (10 sets of twins). In addition, two birth defects were observed in aborted fetuses. However, few of the aborted fetuses were examined. Buspirone was taken during the 1st trimester in 16 pregnancies. The outcomes of these pregnancies included 2 elective abortions, 1 intrauterine death, 12 normal term babies, and 1 newborn with a genetic defect (cystic fibrosis) (3).

In a 1998 case report, a 32-year-old woman with bipolar disorder took buspirone, fluoxetine, and carbamazepine (see Breast Feeding Summary for doses and further details) throughout gestation (4). At 42 weeks' gestation she gave birth to a healthy 3940-g, normally developed female infant. The mother contin ued her medications for 3 weeks while exclusively breast feeding the infant. She reported seizure-like activity in her infant at 3 weeks, 4 months, and 5.5 months of age.

Although no drug-induced congenital malformations have been observed after 1st trimester exposure to buspirone, the data are too limited to assess the safety of the drug in human pregnancy. The cause of the intrauterine death cited above is unknown. Moreover, that study lacked the sensitivity to identify minor anomalies because of the absence of standardized examinations. Late appearing major defects, including neurobehavior effects, may also have been missed due to the timing of the questionnaires.

Breast Feeding Summary

Buspirone and its metabolites, at least one of which is pharmacologically active, are excreted into the milk of lactating rats (1). Only one report has investigated the excretion of buspirone into human milk. In a 1998 case report, a 32-year-old woman with bipolar disorder took buspirone (45 mg/day), fluoxetine (20 mg/day), and carbamazepine (600 mg/day) throughout pregnancy and during the first 3 weeks postpartum (4). She reported seizure-like activity in the infant at 3 weeks, 4 months, and 5.5 months of age. Breast milk, maternal serum, and infant serum were evaluated for buspirone on postpartum day 13, but the drug was not detected in any of the samples (test sensitivity not reported). Similar evaluations were conducted for fluoxetine, norfluoxetine, and carbamazepine on days 13 and 21 postpartum (see Fluoxetine and Carbamazepine for results). A neurologic examination of the infant, that included electroencephalography, was within normal limits. The authors were unable to determine the cause of the seizure-like activity, if it had indeed occurred (none of the episodes had been observed by medical personnel) (4).

Although buspirone was not detected in breast milk or maternal and infant serum in the above case, the timing of the samples in relation to the mother's ingestion of the drug and the test sensitivity were not specified. Therefore, because other agents in this pharmacologic class are excreted into milk (e.g., see Diazepam), the excretion of buspirone, at least to some degree, should still be expected.

Because of the potential for central nervous system impairment in a nursing infant, maternal use of the drug, especially for prolonged periods, should be undertaken cautiously, if at all. The American Academy of Pediatrics classifies other antianxiety agents as drugs whose effects on the nursing infant are unknown, but may be of concern because effects on the developing brain may not be apparent until later in life (5).

References

1. Product information. Buspar. Mead Johnson Pharmaceuticals, 1994.
2. Seifritz E, Holsboer-Trachsler E, Haberthur F, Hemmeter U, Pöldinger W. Unrecognized pregnancy during citalopram treatment. Am J Psychiatry 1993;150:1428–9.
3. Wilton LV, Pearce GL, Martin RM, Mackay FJ, Mann RD. The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England. Br J Obstet Gynaecol 1998;105:882–9.
4. Brent NB, Wisner KL. Fluoxetine and carbamazepine concentrations in a nursing mother/infant pair. Clin Pediatr 1998;37:41–4.
5. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.