What are the effects of Clonazepam (Klonopin) during pregnancy?

From the Guidelines

Klonopin (clonazepam) should be avoided during pregnancy unless the benefits clearly outweigh the risks, due to the potential for increased risks of cleft lip/palate and neonatal withdrawal symptoms 1.

Key Considerations

• Clonazepam is a benzodiazepine that crosses the placenta and may cause harm to the fetus.
• The use of clonazepam during pregnancy may be associated with an increased risk of cleft lip/palate if used in the first trimester.
• Neonatal withdrawal symptoms, including irritability, high-pitched crying, tremors, hyperreflexia, sleep disturbances, and feeding difficulties, may occur if clonazepam is used near delivery.

Alternative Approaches

• For women with anxiety disorders, non-medication approaches like cognitive behavioral therapy should be considered first.
• If medication is necessary during pregnancy, certain SSRIs may have better safety profiles than benzodiazepines.
• For seizure disorders, alternative anti-seizure medications with better pregnancy safety data might be preferable.

Management

• If clonazepam is used during pregnancy, the lowest effective dose should be used, and when possible, the medication should be gradually tapered under medical supervision rather than stopped abruptly.
• Women who are taking clonazepam and are pregnant or planning pregnancy should consult their healthcare provider before making any changes.

Evidence

The potential risks of clonazepam use during pregnancy are supported by studies that have shown an association between benzodiazepine use and increased risks of fetal malformations and neonatal withdrawal symptoms 1. Additionally, the European Respiratory Journal provides guidance on the management of reproduction and pregnancy in women with airways diseases, which includes considerations for the use of medications like clonazepam during pregnancy 1.

From the FDA Drug Label

There are no adequate and well-controlled studies of clonazepam in pregnant women. Available human data on the risk of teratogenicity are inconclusive Administration of benzodiazepines immediately prior to or during childbirth can result in a syndrome of hypothermia, hypotonia, respiratory depression, and difficulty feeding In addition, infants born to mothers who have taken benzodiazepines during the later stages of pregnancy can develop dependence, and subsequently withdrawal, during the postnatal period. In three studies in which clonazepam was administered orally to pregnant rabbits at doses of 0. 2,1,5, or 10 mg/kg/day during the period of organogenesis, a similar pattern of malformations (cleft palate, open eyelid, fused sternebrae and limb defects) was observed at all doses, in a low, non-dose-related incidence

The effects of Clonazepam during pregnancy are not well understood due to a lack of adequate and well-controlled studies in pregnant women. However, available data suggest that:

• Administration of benzodiazepines during pregnancy may result in harmful effects on the fetus, including hypothermia, hypotonia, respiratory depression, and difficulty feeding.
• Infants born to mothers who have taken benzodiazepines during the later stages of pregnancy may develop dependence and withdrawal symptoms during the postnatal period.
• Animal studies have shown a pattern of malformations in offspring when clonazepam was administered to pregnant rabbits. It is essential to weigh the potential benefits and risks of using Clonazepam during pregnancy and to closely monitor the fetus and newborn for any potential adverse effects 2, 2, 2.

From the Research

Effects of Clonazepam on Pregnancy

• The effects of clonazepam on pregnancy are not well understood, with limited studies available 3, 4.
• One study found that clonazepam use during pregnancy did not increase the risk of major malformations, but the sample size was not large enough to determine the safety of the drug 4.
• Another study suggested that benzodiazepines, including clonazepam, should be used with caution during pregnancy, and that the benefits of the drug should be weighed against the potential risks to the fetus 3.

Risks and Considerations

• Clonazepam, like other benzodiazepines, can cross the placenta and may affect the fetus 5.
• The use of clonazepam during the first trimester of pregnancy should be avoided if possible, as this is a critical period of fetal development 6, 7.
• The risk of congenital malformations associated with clonazepam use during pregnancy is not well established, but it is recommended that the drug be used at the lowest effective dose and for the shortest possible duration 3, 4.

Comparison to Other Benzodiazepines

• Diazepam has been found to be relatively safe during pregnancy, but its use during lactation is not recommended due to the risk of lethargy, sedation, and weight loss in infants 3.
• Chlordiazepoxide has been found to be safe during both pregnancy and lactation 3.
• Alprazolam should be avoided during pregnancy and lactation due to the potential risks to the fetus and infant 3.