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

Alprazolam (Xanax), bromazepam (Lectopam), chlordiazepoxide (Librium), clonazepam (Rivotril), diazepam (Valium), flunitrazepam (Rohypnol), flurazepam (Dalmane), lorazepam (Ativan), midazolam (Versed), nitrazepam (Mogadon), oxazepam (Serax), temazepam (Restoril), triazolam (Halcion)

Street names

Benzos, tranks, downers

Benzodiazepines are frequently used to treat anxiety disorders,^* which affect approximately 1.9 million people in Canada each year.¹ These disorders occur in women significantly more often than in men;¹ consequently, many women of childbearing age may be taking a benzodiazepine when they become pregnant.

These drugs have anticonvulsant, anxiolytic, hypnotic and sedative properties. They are used to manage anxiety disorders (including panic disorder), insomnia, seizure disorders, skeletal muscle spasticity and alcohol withdrawal, and as premedicants prior to surgical or diagnostic procedures. Benzodiazepines have also been used to manage nausea and vomiting associated with emetogenic cancer chemotherapy.

*SSRIs and SNRIs, not benzodiazepines, are generally the preferred firstline treatment for long-standing anxiety disorders.

Summary and Recommendations

A woman who requires benzodiazepines during pregnancy or who has taken them prior to becoming pregnant should be advised of the conflicting information (see below), and helped to weigh the benefits of such treatment against the risks.
A level II ultrasound can be performed to rule out visible forms of oral clefts.
To minimize discontinuation effects on the neonate, the dose can be decreased during late pregnancy.
During breastfeeding, the infant should be monitored for any adverse effects (e.g., drowsiness, difficulty feeding).

Fetal effects

Major malformations

Overall, there is insufficient evidence that benzodiazepines are human teratogens.^2–6 A meta-analysis of 23 studies⁵ addressed the risk for congenital malformations with the use of benzodiazepines during the first trimester of pregnancy. Pooled data from the case-controlled studies revealed a marginally significant two-fold increase in the risk of major malformations and oral cleft specifically. However, the case-controlled studies were heterogeneous, which decreases the results’ reliability. Pooled data from the cohort studies, on the other hand, revealed no association between fetal exposure to benzodiazepines and the risk of oral clefts or any other major malformations.

The absolute risk for clefts, if present, remains small (i.e., the incidence of oral clefts in the general population is about one per thousand; the two-fold increase is therefore two per thousand).

Spontaneous abortion

No data are available on benzodiazepines and spontaneous abortion.

Neonatal effects

Babies exposed in utero to benzodiazepines should be watched carefully after birth for signs of abrupt discontinuation syndrome. This syndrome may include sedation, hypotonia, reluctance to suck, apnea, cyanosis and impaired metabolic responses to cold stress. The effects are self-limiting.

Long-term effects on the child

There have been no reports of long-term adverse effects on the intelligence quotient or neurodevelopment of children born to mothers who took benzodiazepines during pregnancy.

Breastfeeding

Most benzodiazepines are excreted into breast milk at low concentrations (less than five per cent of the maternal dose).⁴ It is preferable to use the newer short-acting preparations (e.g., lorazepam) and avoid agents with a long half-life (e.g., diazepam); however, the short-acting benzodiazepines are more addictive.

Withdrawal effects on the mother

Women who suddenly stop taking a benzodiazepine may experience symptoms of abrupt discontinuation, including withdrawal symptoms or a re-emergence of the underlying illness. Symptoms may last for weeks or months and can occur when therapeutic doses are suddenly stopped. People who take benzodiazepines daily are at risk for withdrawal if they have been taking therapeutic doses for at least two months,⁷ or excessive doses for at least two weeks.

Withdrawal symptoms start one to two days after short-acting benzodiazepines have been stopped and two to four days after long-acting benzodiazepines are discontinued. Symptoms commonly fall into two groups:

anxiety-related symptoms—such as irritability, palpitations, panic attacks, labile mood, restlessness and insomnia
neurological symptoms—including perceptual disturbances, primarily visual and auditory (e.g., sounds are unpleasantly loud, colours are harsh, staircases look longer than they actually are); odd sensations such as depersonalization, derealization, déjà vu and dysperceptions; and seizures, psychosis and delirium.

These symptoms can last for many weeks. In addition, patients often report feeling fragile, with rapid shifts in emotions.

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

One study compared the rates of major malformations between treated and untreated women with panic disorder. This study found a higher rate of isolated oral cleft and multiple congenital abnormalities in the children of mothers with the untreated panic disorder.⁶ The authors concluded that anti-panic drug treatment appears to have a protective effect.

References

Health Canada. (2002). Anxiety disorders. In A Report on Mental Illnesses in Canada. Ottawa: Author. Available: www.mooddisorderscanada.ca/ report/english/chapter4/index.htm. Accessed June 29, 2007.
Czeizel, A. (1987). Lack of evidence of teratogenicity of benzodiazepine drugs in Hungary. Reproductive Toxicology, 1 (3), 183–188.
Bergman, U., Rosa, F.W., Baum, C., Wiholm, B.E. & Faich, G.A. (1992). Effects of exposure to benzodiazepine during fetal life. Lancet, 340 (8821), 694–696.
McElhatton, P.R. (1994). The effects of benzodiazepine use during pregnancy and lactation. Reproductive Toxicology, 8 (6), 461–475.
Dolovich, L.R., Addis, A., Vaillancourt, J.M., Power, J.D., Koren, G. & Einarson, T.R. (1998). Benzodiazepine use in pregnancy and major malformations or oral cleft: Meta-analysis of cohort and case-control studies. British Medical Association Journal, 317 (7162), 839–843.
Acs, N., Banhidy, F., Horvath-Puho, E. & Czeizel, A.E. (2006). Maternal panic disorder and congenital abnormalities: A population-based case-control study. Birth Defects Research. Part A, Clinical and Molecular Teratology, 76 (4), 253–261.
Kahan, M. & Wilson, L. (2002). Managing Alcohol, Tobacco and Other Drug Problems: A Pocket Guide for Physicians and Nurses. Toronto: Centre for Addiction and Mental Health.
Pien, G.W. & Schwab, R.J. (2004). Sleep disorders during pregnancy. Sleep, 27 (7), 1405–1417.