Is diphenhydramine (Benadryl) safe for long-term use as a sleep aid?

Diphenhydramine is Not Recommended for Long-Term Use as a Sleep Aid

Diphenhydramine (Benadryl) is not recommended for long-term use as a sleep aid due to lack of proven efficacy and potential safety concerns. 1

Evidence Against Long-Term Use

• The American Academy of Sleep Medicine (AASM) explicitly recommends against using diphenhydramine for treating sleep onset and sleep maintenance insomnia in adults (weak recommendation) 1
• Clinical studies show that diphenhydramine's effects on sleep parameters fall below clinically significant improvement thresholds 1
• The benefits and harms of diphenhydramine are judged to be approximately equal, with insufficient evidence of meaningful clinical benefit 1
• The FDA has not approved diphenhydramine for long-term use as a sleep aid, and its labeling includes multiple warnings about potential adverse effects 2

Specific Concerns with Long-Term Use

• Diphenhydramine can cause marked drowsiness, which may impair driving ability and operation of machinery 2
• It may interact with alcohol, sedatives, and tranquilizers, increasing drowsiness 2
• First-generation antihistamines like diphenhydramine have many side effects including sedation and risk of toxicity in overdose including cardiac toxicity 3
• The 2015 Beers Criteria for Potentially Inappropriate Medication Use in Older Adults specifically recommends that individuals 65 years or older avoid diphenhydramine 4

Efficacy Limitations

• Meta-analyses of clinical trials show that diphenhydramine provides only minimal improvements in sleep parameters:
  • The mean reduction in patient-reported sleep latency versus placebo falls below clinically significant improvement 1
  • Small increases in total sleep time also fall below the threshold for clinical significance 1
  • Polysomnography (PSG) measurements confirm that improvements in sleep latency and total sleep time are not clinically significant 1

Alternative Approaches for Insomnia

• Cognitive behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for chronic insomnia by both the AASM and the American College of Physicians 1, 5
• If pharmacological treatment is necessary after CBT-I failure, the AASM suggests:
  • For sleep onset insomnia: zaleplon, zolpidem, ramelteon, or triazolam 1, 5
  • For sleep maintenance insomnia: eszopiclone, zolpidem, temazepam, or doxepin 1, 5
• Orexin receptor antagonists like suvorexant and lemborexant are newer options for sleep maintenance insomnia 6, 5

Special Considerations for Older Adults

• Diphenhydramine is particularly problematic for older adults, with more than half of older adults using over-the-counter sleep medications taking products containing diphenhydramine or doxylamine despite recommendations against this practice 4
• Many older adults are unaware of the safety risks associated with these medications 4
• The Veterans Administration and Department of Defense Clinical Practice Guidelines also recommend against diphenhydramine for chronic insomnia disorder 1

Conclusion for Clinical Practice

• For short-term, occasional insomnia, some evidence suggests diphenhydramine may provide modest benefits 7, 8, 9
• However, for chronic insomnia requiring long-term management, diphenhydramine should be avoided in favor of evidence-based alternatives 1, 5
• When pharmacological treatment is necessary, it should be used as part of a shared decision-making approach after discussing benefits, harms, and costs 1