What is the evidence for the use of doxylamine (antihistamine) in treating insomnia during pregnancy?

Doxylamine for Insomnia in Pregnancy: Evidence Assessment

Doxylamine is not recommended as a first-line treatment for insomnia during pregnancy due to limited efficacy data and potential safety concerns, though it may be considered in specific situations when the benefits outweigh the risks. 1

Safety Profile in Pregnancy

Doxylamine has been extensively studied for nausea and vomiting in pregnancy (NVP), showing a favorable safety profile when used in combination with pyridoxine:

• The FDA has approved doxylamine-pyridoxine combination (Diclegis®) for NVP, with studies demonstrating maternal safety 2
• According to the American College of Obstetricians and Gynecologists (ACOG), H1-receptor antagonists like doxylamine are considered safe first-line pharmacologic therapies for persistent nausea and vomiting in pregnancy 3

However, when considering its use specifically for insomnia:

• The FDA label for doxylamine advises pregnant women to consult a healthcare professional before use 4
• While case-control studies examining doxylamine use during pregnancy are generally reassuring regarding birth defects 5, its use specifically for insomnia has not been as thoroughly evaluated

Efficacy for Insomnia

The evidence for doxylamine's efficacy in treating insomnia is limited:

• The American Academy of Sleep Medicine (AASM) suggests that clinicians not use diphenhydramine (a similar first-generation antihistamine) for sleep onset and maintenance insomnia due to limited efficacy 3
• Small comparative trials of doxylamine showed no major efficacy difference versus benzodiazepines, but with notable side effects including daytime drowsiness, altered vigilance, and anticholinergic effects 5

First-Line Approaches for Insomnia in Pregnancy

1. Non-pharmacological interventions:

   • Cognitive Behavioral Therapy for Insomnia (CBT-I) is the first-line treatment for insomnia, including during pregnancy 1, 6
   • Digital CBT-I during pregnancy has shown benefits for postpartum insomnia remission and may prevent postpartum depression and anxiety 6
   • Sleep hygiene education, stimulus control, and relaxation techniques should be implemented first

2. If medication is necessary:

   • Consider the risk-benefit profile for both mother and fetus
   • Chlorphenamine is often chosen by clinicians in the UK when antihistamine therapy is necessary because of its long safety record 3
   • Loratadine and cetirizine are classified as FDA Pregnancy Category B drugs, implying no evidence of harm to the fetus during pregnancy 3

Algorithm for Managing Insomnia in Pregnancy

1. First step: Non-pharmacological approaches

   • Implement CBT-I techniques
   • Ensure proper sleep hygiene
   • Use relaxation techniques and stimulus control

2. If pharmacological intervention is necessary:

   • Evaluate severity of insomnia and impact on maternal functioning
   • Consider intermittent use of medications on an as-needed basis to minimize fetal exposure 3
   • For short-term use, doxylamine may be considered if:
     • The patient has failed non-pharmacological approaches
     • Insomnia is significantly impacting maternal health
     • Benefits outweigh potential risks

3. Monitoring and follow-up:

   • Limit use to the lowest effective dose for the shortest duration
   • Schedule follow-up within 7-10 days to evaluate treatment response 1
   • Monitor for side effects including daytime drowsiness and anticholinergic effects

Important Precautions

• Avoid using doxylamine if the patient has:
  • Breathing problems such as asthma or chronic bronchitis
  • Glaucoma
  • Urinary retention or prostate enlargement 4
• Avoid alcohol when using doxylamine 4
• If insomnia persists continuously for more than two weeks, reevaluate for underlying medical conditions 4
• Consider that sedating antihistamines can cause daytime sedation, impairment, and anticholinergic side effects 1

Conclusion

While doxylamine has demonstrated safety for nausea and vomiting in pregnancy, its use specifically for insomnia should be approached with caution. Non-pharmacological approaches like CBT-I should be the first line of treatment, with pharmacological options considered only when necessary and after careful risk-benefit assessment.