Diphenhydramine Should Not Be Used for Insomnia During Pregnancy
Diphenhydramine is not recommended for treating insomnia during pregnancy due to both its lack of efficacy for sleep disorders and safety concerns, particularly during the first trimester. 1, 2
Primary Recommendation Against Use
The American Academy of Sleep Medicine explicitly recommends against using diphenhydramine for treating either sleep onset or sleep maintenance insomnia in adults, finding that its benefits and harms are approximately equal with insufficient evidence of meaningful clinical benefit. 1, 3 This recommendation applies regardless of pregnancy status, but pregnancy adds additional safety concerns that further strengthen the case against its use.
Efficacy Concerns
- Diphenhydramine provides only minimal sleep improvements: mean reduction in sleep latency of just 8 minutes compared to placebo, and total sleep time improvement of only 12 minutes—both falling below clinically significant thresholds. 1
- There is no improvement in quality of sleep compared to placebo. 1
- These marginal benefits do not justify the risks, especially in pregnancy. 3
Pregnancy-Specific Safety Concerns
First Trimester Risks
- The American College of Allergy, Asthma, and Immunology recommends using diphenhydramine with caution during pregnancy, particularly in the first trimester, due to concerns about a possible association with cleft palate. 2
- The first trimester is the most critical period for concern about congenital malformations because this is when organogenesis occurs. 2
- Although recent studies have not conclusively confirmed the cleft palate risk, the concern has not been sufficiently refuted. 2
- If diphenhydramine must be used, avoid the first trimester. 2
FDA Labeling
The FDA drug label advises pregnant women to "ask a healthcare professional before use," indicating that diphenhydramine is not considered safe without medical consultation during pregnancy. 4
Recommended Alternatives for Insomnia in Pregnancy
First-Line Approach
Cognitive behavioral therapy for insomnia (CBT-I) should be the first-line treatment for insomnia during pregnancy. 3, 5 This nonpharmacologic approach avoids any teratogenic risk while addressing the underlying sleep disturbance.
If Pharmacotherapy Is Necessary
When medication is required and antihistamine treatment is deemed necessary:
- Chlorpheniramine is the preferred first-choice antihistamine during pregnancy due to its observed safety and long track record of use. 2
- Cetirizine and loratadine (FDA Pregnancy Category B) have more accumulated safety data than diphenhydramine and may be preferred alternatives. 2
- These second-generation antihistamines have confirmed safety through large birth registries, case-control studies, and cohort studies. 2
For Insomnia Specifically (Non-Pregnant Recommendations)
If insomnia treatment requires pharmacotherapy outside of pregnancy, the American Academy of Sleep Medicine suggests:
- For sleep onset insomnia: zaleplon, zolpidem, ramelteon, or triazolam 3
- For sleep maintenance insomnia: eszopiclone, zolpidem, temazepam, or doxepin 3
However, the safety profiles of these medications during pregnancy require individual assessment and are beyond the scope of diphenhydramine-specific guidance.
Critical Pitfalls to Avoid
- Do not assume diphenhydramine is safe simply because it is available over-the-counter. 1, 2
- Do not combine antihistamines with oral decongestants during the first trimester due to potential risks of congenital malformations. 2
- Do not assume all antihistamines have equivalent safety profiles during pregnancy—they do not. 2, 6
- Avoid using diphenhydramine as a long-term sleep aid even outside of pregnancy, as it lacks evidence of clinically meaningful benefit. 1, 3
Monitoring If Diphenhydramine Is Used Despite Recommendations
If diphenhydramine must be used during pregnancy despite these recommendations: