Anxiolytics/sedatives (non-benzodiazepines)

From: Exposure to Psychotropic Medications and Other Substances during Pregnancy and Lactation: A Handbook for Health Care Providers

On this page:

Summary and recommendations
Fetal effects
Neonatal effects
Long-term effects on the child
Breastfeeding
Withdrawal effects on the mother
Effects of untreated illness

Examples

Buspirone (BuSpar); zopiclone (Imovane)

Buspirone is a psychotropic drug with anxiolytic properties, chemically unrelated to any other anti-anxiety drug, and is used to treat anxiety disorders. Zopiclone is used as an alternative treatment to benzodiazepines for the symptomatic relief of transient and short-term insomnia. Zopiclone is structurally unrelated but pharmacologically similar to benzodiazepines.

Summary and Recommendations

Due to the lack of information about the use of buspirone in pregnancy and breastfeeding, it is not recommended as a drug of choice. However, if a woman is taking it and becomes pregnant, the provider should not be unduly concerned because there has been no evidence, in either animal studies or case reports, that this drug increases risk for adverse outcomes.
While insufficient data is available to fully assess the safety of zopiclone during pregnancy, short-term use for treatment of insomnia does not appear to present undue risk.
Zopiclone is considered safe for use during breastfeeding.

Fetal effects

Major malformations

Seventeen case reports show no evidence of buspirone increasing risk for major malformations.^1,2 One observational cohort study suggests that zopiclone does not appear to be a major human teratogen.³ However, sufficient data is not available on either of these medications to firmly establish whether they affect the fetus during pregnancy.⁴

Spontaneous abortion

There are no studies on whether either buspirone or zopiclone increases the risk for spontaneous abortion.

Neonatal effects

While there are reports that certain benzodiazepines taken during the last weeks of pregnancy have resulted in neonatal central nervous system depression,⁵ whether or not buspirone or zopiclone could cause similar effects remains unknown. There are no case reports of adverse effects in neonates associated with the use of these non-benzodiazepine anxiolytic drugs during pregnancy.

The results of a 1999 prospective observational study on zopiclone showed no differences between the study and control groups in pregnancy outcome, fetal distress, presence of meconium at birth, preterm deliveries or neonatal intensive care admissions.³

Long-term effects on the child

There are no long-term studies available on the effects on the child of buspirone or zopiclone exposure in utero.

Breastfeeding

Buspirone and its metabolites are excreted into milk in rats, but no data exists on whether buspirone is excreted into human breast milk.⁶ The average infant dose of zopiclone ingested through breast milk has been calculated at 1.4 per cent of the maternal dose.⁷ Zopiclone is therefore considered compatible with breastfeeding.

Withdrawal effects on the mother

While withdrawal effects have not been reported with buspirone, there is a risk that anxiety symptoms may recur after abrupt discontinuation.

Withdrawal symptoms have been reported in individuals who used therapeutic or high doses of zopiclone over more than a two-week period and then abruptly discontinued use.⁴ Withdrawal symptoms include rebound insomnia and anxiety, mild dysphoria and, rarely, a major withdrawal syndrome, including abdominal and muscle cramps, vomiting, sweating, tremor and convulsions.

Effects of untreated illness

There are no definitive studies on the effect of untreated anxiety or insomnia in pregnancy or postpartum.

During all three trimesters of pregnancy it is normal for women to experience changes in sleep for a variety of reasons, including high hormone levels and physical changes. The greatest sleep disturbance is typically in the first month postpartum. This may increase the risk of postpartum depression and psychosis, though this hypothesis has not been studied extensively.⁸

References

Wilton, L.V., Pearce, G.L., Martin, R.M., Mackay, F.J. & Mann, R.D. (1998). The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England. British Journal of Obstetrics and Gynaecology, 105 (8), 882–889.
McElhatton, P.R., Garbis, H.M., Elefant, E., Vial, T., Bellemin, B., Mastroiacovo, P. et al. (1996). The outcome of pregnancy in 689 women exposed to therapeutic doses of antidepressants. A collaborative study of the European Network of Teratology Information Services (entis). Reproductive Toxicology, 10 (4), 285–294.
Diav-Citrin, O., Okotore, B., Lucarelli, K. & Koren, G. (1999). Pregnancy outcome following first-trimester exposure to zopiclone: A prospective controlled cohort study. American Journal of Perinatology, 16 (4), 157–160.
Sanofi-Aventis Canada. (2006). Imovane (zopiclone): Product monograph. Laval, QU: Author.
McElhatton, P.R. (1994). The effects of benzodiazepine use during pregnancy and lactation. Reproductive Toxicology, 8 (6), 461–475.
Bristol-Myers Squibb Canada. (2004). BuSpar (buspirone): Product monograph. Montreal: Author.
Hale, T.W. (2006). Medications and Mothers’ Milk: A Manual of Lactational Pharmacology (12th ed.). Amarillo, TX: Hale Publishing.
Pien, G.W. & Schwab, R.J. (2004). Sleep disorders during pregnancy. Sleep, 27 (7), 1405–1417.