How does ZzzQuil (diphenhydramine) impact sleep architecture?

ZzzQuil (Diphenhydramine) Has Minimal and Clinically Insignificant Effects on Sleep Architecture

The American Academy of Sleep Medicine explicitly recommends against using diphenhydramine (the active ingredient in ZzzQuil) for treating insomnia because it produces no meaningful improvement in sleep architecture and provides only clinically insignificant changes in sleep parameters. 1

Objective Sleep Architecture Effects

Diphenhydramine at 50 mg doses demonstrates the following effects on polysomnographic (PSG) sleep parameters:

Sleep Latency

• Mean reduction of only 8 minutes compared to placebo (95% CI: 2 min increase to 17 min reduction) 1
• This falls below the threshold for clinical significance 1

Total Sleep Time

• Mean improvement of only 12 minutes compared to placebo (95% CI: 13 min reduction to 38 min improvement) 1
• This minimal increase is not clinically meaningful 1

Sleep Efficiency

• Objective sleep efficiency was actually reduced by 0.53% (95% CI: -0.02 to -1.05%) 1
• This represents a worsening rather than improvement in sleep quality

Number of Awakenings

• PSG-measured awakenings mildly increased by 0.5 awakenings (95% CI: -1.29 to +2.29) 1
• Subjective awakenings minimally reduced by 0.21 awakenings (95% CI: -0.9 to +0.48), below clinical significance 1

Quality of Sleep

• No improvement in quality of sleep compared to placebo 1
• Standardized mean difference of +0.48 (CI: -0.5 to +1.46), which falls below clinical significance 1

Critical Clinical Implications

Diphenhydramine provides sedation without restorative sleep benefits - it does not improve the actual architecture or quality of sleep. 2

Tolerance Development

• Children and adults develop tolerance to the sedating properties of antihistamines like diphenhydramine 2
• Antimuscarinic and anticholinergic side effects persist even after tolerance develops 2, 3
• At best, sedating antihistamines improve global sleep assessments in only 26% of patients 2, 3

Evidence Quality

• Overall quality of evidence was downgraded to very low due to significant heterogeneity, imprecision, and potential publication bias 1
• Benefits and harms are judged to be approximately equal, with insufficient evidence of meaningful clinical benefit 1, 4

Guideline Recommendations

The American Academy of Sleep Medicine suggests clinicians NOT use diphenhydramine as treatment for sleep onset and sleep maintenance insomnia (WEAK recommendation). 1, 4

This recommendation is based on:

• Absence of clinically significant improvement in any sleep parameter 1, 4
• The majority of well-informed patients would not choose diphenhydramine over no treatment 1
• Veterans Administration and Department of Defense Clinical Practice Guidelines also recommend against diphenhydramine for chronic insomnia 4

Common Pitfall to Avoid

Do not prescribe diphenhydramine expecting improvement in sleep architecture - it provides sedation that patients may interpret as "sleep," but objective measurements show no meaningful restoration of normal sleep structure. 2 The subjective feeling of sedation does not translate to improved sleep quality or architecture.

Evidence-Based Alternatives

For patients requiring pharmacological treatment for insomnia, the American Academy of Sleep Medicine recommends:

For Sleep Onset Insomnia:

• Zaleplon, zolpidem, ramelteon, or triazolam 4

For Sleep Maintenance Insomnia:

• Eszopiclone (28-57 min TST improvement), zolpidem (29 min TST improvement), temazepam (99 min TST improvement), or doxepin (26-32 min TST improvement) 1, 4

First-Line Treatment:

• Cognitive behavioral therapy for insomnia (CBT-I) is recommended as first-line treatment by the American College of Physicians 4