Are any sleep aids safe to use during pregnancy?

Sleep Aids in Pregnancy

Diphenhydramine and doxylamine are the safest pharmacologic sleep aids during pregnancy, with doxylamine having the most reassuring safety data, while benzodiazepines should be avoided particularly in the first trimester due to potential teratogenic risks. 1, 2, 3

First-Line Approach: Non-Pharmacologic Management

Before considering any medication, behavioral interventions should be attempted as they are equally effective to benzodiazepines with longer-lasting benefits and no fetal risk 3:

• Stimulus control therapy has similar efficacy to benzodiazepines but with sustained effects and no adverse outcomes 3
• Sleep hygiene education addressing misconceptions about sleep physiology helps reduce anxiety that perpetuates insomnia 4, 3
• Moderate morning exercise may provide benefit, though evidence is limited 3

Pharmacologic Options When Non-Pharmacologic Measures Fail

Safest Options: Antihistamines

Doxylamine (first choice):

• Has the most reassuring pregnancy safety data among sleep aids 3
• Case-control studies show no association with birth defects 3
• FDA labeling advises consulting a healthcare professional before use in pregnancy but does not contraindicate it 2
• Main adverse effects include daytime drowsiness and anticholinergic effects 3

Diphenhydramine (second choice):

• Small comparative trials show similar efficacy to benzodiazepines 3
• FDA labeling recommends asking a healthcare professional before use in pregnancy 1
• Should not be used to make children sleepy and causes marked drowsiness 1
• Adverse effects include daytime drowsiness and anticholinergic symptoms 3

Medications to Avoid

Benzodiazepines:

• Should be avoided, particularly in the first trimester 5, 3
• Case-control studies suggest a 2-fold increased risk of oral cleft defects 5
• If absolutely necessary, midazolam is preferred over other benzodiazepines 5
• Cause dependence, withdrawal syndrome, memory disorders, falls, and fractures 3
• Efficacy is uncertain beyond two weeks due to rapid tolerance development 3

NSAIDs (including over-the-counter options):

• Must be discontinued after gestational week 28 due to serious fetal risks 6
• Can cause premature closure of ductus arteriosus, oligohydramnios, and pulmonary hypertension in third trimester 6, 7
• Women may not realize common pain relievers like ibuprofen are NSAIDs and could consider them safe sleep aids 7

Clinical Decision Algorithm

1. Start with non-pharmacologic interventions (stimulus control, sleep hygiene) for all pregnant patients with insomnia 4, 3

2. If pharmacotherapy is necessary:

   • First trimester: Doxylamine is preferred; avoid benzodiazepines due to cleft risk 3
   • Second trimester: Doxylamine remains the safest option 3
   • Third trimester: Doxylamine continues to be safe; absolutely avoid NSAIDs after week 28 6, 3

3. Use lowest effective dose for shortest duration to minimize any potential risks 8, 9

4. Counsel patients that over-the-counter medications are not risk-free and require the same careful consideration as prescription medications 1, 2

Important Caveats

• Insomnia is under-detected in pregnancy: Only 39% of pregnant women report discussing sleep with providers, and among those with moderate-to-severe insomnia, only 57% discussed it 10
• Treatment recommendations often don't match guidelines: Over-the-counter medications are most commonly recommended (53%) despite cognitive behavioral therapy being preferred 10
• Risk-benefit analysis is essential: The risks of untreated insomnia (adverse pregnancy outcomes, maternal distress) must be weighed against medication risks 8, 9, 4
• Limited data exists: Most sleep aid safety data in pregnancy comes from observational studies rather than randomized trials 8, 9
• Breastfeeding considerations: Both diphenhydramine and doxylamine pass into breast milk in trace amounts; avoid in neonates with jaundice 5, 1, 2