Is hydroxyzine (an antihistamine) safe for anxiety treatment during pregnancy?

Hydroxyzine for Anxiety in Pregnancy

Hydroxyzine is contraindicated in early pregnancy and should not be used for anxiety treatment at any stage of pregnancy. 1

FDA Contraindication

The FDA drug label explicitly states that hydroxyzine is contraindicated in early pregnancy because it induced fetal abnormalities in rats and mice at doses substantially above the human therapeutic range, and clinical data in humans are inadequate to establish safety. 1 This represents the strongest regulatory warning against its use during pregnancy.

Guideline Consensus Against Hydroxyzine

• British guidelines explicitly identify hydroxyzine as the only antihistamine specifically contraindicated during the early stages of pregnancy. 2
• U.S. allergy guidelines list hydroxyzine among medications to avoid during pregnancy, particularly in the first trimester. 2
• This contraindication is based on animal data showing potential teratogenic risks, even though the doses used were substantially above human therapeutic ranges. 1

Safer Alternatives for Anxiety in Pregnancy

First-Line Antihistamine Options (if considering antihistamines for anxiety-related sedation):

• Cetirizine is the active metabolite of hydroxyzine and represents a safer alternative with a long safety record and no significant increase in congenital malformations during first trimester exposure. 2
• Chlorpheniramine has been specifically recommended as a first-choice agent during pregnancy with sufficient human observational data demonstrating no significant increase in congenital malformations when used during the first trimester. 2
• Loratadine is confirmed safe through large birth registries, case-control studies, and cohort studies. 2

Antidepressants for Anxiety Treatment:

• Sertraline and citalopram at low doses appear more favorable for anxiety disorders in pregnancy based on their safety profiles and efficacy data. 3
• Antidepressants are generally considered relatively safe when used during pregnancy and can be used as alternatives for treating anxiety. 4
• SSRIs represent a more appropriate pharmacological approach for anxiety disorders in pregnancy compared to benzodiazepines or hydroxyzine. 5

Non-Pharmacological Approaches:

• Cognitive-behavioral therapy should be first-line treatment in pregnant women with anxiety disorders whenever possible. 5
• Psychotherapy is a potential alternative to medication for the treatment of anxiety disorders. 4

Critical Clinical Considerations

• The first trimester is the most critical period for concern about medication-induced congenital malformations due to organogenesis. 2
• Untreated maternal psychiatric illness can have adverse effects on pregnancy outcome and infant well-being, so treatment decisions must balance risks of medication against risks of untreated anxiety. 4
• Benzodiazepines, while sometimes used for anxiety, have a small but significant risk of birth defects and should generally be avoided. 4

Common Pitfalls to Avoid

• Do not assume hydroxyzine is safe simply because it is an antihistamine - it is the only antihistamine with a specific contraindication in pregnancy. 2
• Do not substitute hydroxyzine with cetirizine without proper evaluation - while cetirizine is safer, anxiety disorders typically require more comprehensive treatment than antihistamines alone. 2, 3
• Avoid combining any antihistamines with oral decongestants during the first trimester due to associations with gastroschisis and small intestinal atresia. 2