Can a patient take an alternative to diphenhydramine (Benadryl) for sleep?

Yes, Patients Should Use Evidence-Based Alternatives to Diphenhydramine for Sleep

The American Academy of Sleep Medicine explicitly recommends against using diphenhydramine for treating either sleep onset or sleep maintenance insomnia in adults, and clinicians should instead prescribe FDA-approved hypnotics with proven efficacy. 1, 2

Why Diphenhydramine Should Not Be Used

Diphenhydramine demonstrates minimal clinical benefit for insomnia:

• Sleep latency reduction: Only 8 minutes compared to placebo (confidence interval crosses zero, meaning it may provide no benefit at all) 1
• Total sleep time increase: Only 12 minutes compared to placebo, falling well below the 20-minute threshold for clinical significance 1
• Sleep quality: No improvement compared to placebo 1
• Overall assessment: Benefits are judged approximately equal to harms, with insufficient evidence of meaningful clinical benefit 1, 2

The Veterans Administration and Department of Defense Clinical Practice Guidelines also recommend against diphenhydramine for chronic insomnia 2.

Recommended Alternatives Based on Sleep Pattern

The American Academy of Sleep Medicine provides clear, evidence-based recommendations for specific sleep problems 1:

For Sleep Onset Insomnia (Difficulty Falling Asleep):

First-line options:

• Zolpidem 10 mg (5 mg in women, elderly, or hepatic impairment): Reduces sleep latency by 29 minutes, with moderate improvement in sleep quality 1, 3
• Zaleplon 10 mg (5 mg in elderly/debilitated): Short-acting, ideal for sleep onset 1
• Ramelteon 8 mg: Melatonin receptor agonist with no short-term usage restrictions 1
• Triazolam 0.25 mg (0.125 mg in elderly): Short-acting benzodiazepine 1

For Sleep Maintenance Insomnia (Staying Asleep):

First-line options:

• Eszopiclone 2-3 mg (1 mg in elderly): Improves total sleep time by 28-57 minutes with moderate-to-large improvement in sleep quality 1
• Temazepam 15-30 mg (7.5 mg in elderly): Improves total sleep time by 99 minutes 1
• Doxepin 3-6 mg: Low-dose formulation reduces wake after sleep onset by 14-30 minutes 1
• Zolpidem extended-release 12.5 mg (6.25 mg in elderly/debilitated): For both sleep onset and maintenance 1

For Both Sleep Onset and Maintenance:

Suvorexant 10-20 mg: Orexin receptor antagonist that improves total sleep time by 10 minutes and reduces wake after sleep onset by 16-28 minutes 1

Special Populations

Elderly patients require particular caution 1:

• Use half the standard adult dose for most hypnotics
• Avoid flurazepam due to extended half-life and risk of residual daytime drowsiness 1
• Benzodiazepines should not be used routinely in elderly patients 4

Patients with hepatic impairment 3:

• Reduce zolpidem to 5 mg
• Avoid use in severe hepatic impairment

What About Other Common "Sleep Aids"?

Melatonin (2 mg): Also not recommended by the American Academy of Sleep Medicine, as it reduces sleep latency by only 9 minutes with very low quality evidence 1. While one integrative review suggests it may be helpful 5, the highest quality guideline evidence does not support its use for insomnia 1.

Trazodone (50 mg): Not recommended—reduces sleep latency by only 10 minutes with no improvement in sleep quality compared to placebo 1

Sedating antidepressants (trazodone, mirtazapine, doxepin, amitriptyline): Should only be considered when accompanied by comorbid depression or after other treatment failures, with evidence for efficacy being relatively weak 1

Critical Caveats

• Allow adequate sleep time: Patients must have 7-8 hours remaining before planned awakening to avoid next-day impairment 3
• Take on empty stomach: Maximizes effectiveness of hypnotics 1
• Avoid alcohol and CNS depressants: Additive effects on psychomotor performance 1
• Pregnancy/nursing: Hypnotics not recommended 1
• Respiratory compromise: Use caution in asthma, COPD, or sleep apnea 1

The Optimal Approach

Cognitive behavioral therapy for insomnia (CBT-I) should be first-line treatment before any pharmacological intervention 2. When medication is necessary, use FDA-approved hypnotics with proven efficacy rather than diphenhydramine, which lacks meaningful clinical benefit for insomnia 1, 2.