What are the long-term risks of using Sleep-Eze (diphenhydramine)?

Long-Term Risks of Sleep-Eze (Diphenhydramine) Use

Diphenhydramine (Sleep-Eze) should be avoided for long-term use due to significant risks of cognitive impairment, anticholinergic effects, and potential for falls and injuries, particularly in older adults. 1

Major Long-Term Risks

Cognitive Effects

• Delirium and cognitive impairment 1
• Memory disorders and slowed comprehension 1
• Increased risk of cognitive decline in older adults 2
• Confusion and disorientation (5-fold increase compared to placebo) 1

Physical Risks

• Falls and injuries due to sedation and balance impairment 1
• Dizziness and loss of balance (3-fold increase compared to placebo) 1
• Impaired vision 1
• Residual morning sedation affecting driving ability (4-fold increase) 1, 3

Anticholinergic Effects

• Urinary retention 1, 3
• Constipation 1
• Dry mouth and blurred vision 1

Other Significant Concerns

• Daytime drowsiness affecting quality of life 1, 4
• Potential for tolerance development 4
• Possible association with dementia with long-term use 1
• Altered vigilance affecting daily functioning 4

Risk Factors for Adverse Effects

The risk of adverse effects is significantly higher in:

1. Older adults (≥65 years) - particularly vulnerable to cognitive effects 1, 2
2. Patients with comorbidities such as:
   • Glaucoma 3
   • Prostatic hypertrophy 3
   • Breathing problems like chronic bronchitis 3
3. Patients taking other medications:
   • Sedatives or tranquilizers (increased drowsiness) 3
   • Other anticholinergic medications (additive effects) 1
4. Alcohol users (potentiates sedative effects) 3

Efficacy Concerns

Despite widespread use, diphenhydramine has limited evidence supporting its long-term efficacy:

• The American Academy of Sleep Medicine explicitly recommends against diphenhydramine for treating either sleep onset or sleep maintenance insomnia 1
• Shows minimal improvement in sleep quality compared to placebo 1
• Mean sleep latency reduction is only 8 minutes compared to placebo 1
• Mean total sleep time improvement is only 12 minutes compared to placebo 1

Special Population Considerations

Elderly Patients

• The American Geriatric Society Beers criteria recommends avoiding anticholinergic medications like diphenhydramine in older adults 1
• Increased risk of cognitive impairment, falls, and anticholinergic effects 1, 2
• A study of rural older adults showed significant association between diphenhydramine use and cognitive impairment 2

Women of Childbearing Age

• Should avoid during pregnancy unless specifically advised by healthcare provider 3
• Caution during breastfeeding 3

Alternative Approaches

For those seeking sleep improvement, safer alternatives include:

1. Cognitive Behavioral Therapy for Insomnia (CBT-I) - first-line treatment with similar efficacy to benzodiazepines but longer-lasting effects 4
2. Sleep hygiene education - explaining basic sleep physiology and addressing misconceptions 4
3. Stimulus control - more effective and safer than medication for long-term management 4
4. Regular physical exercise, especially in the morning 4

Conclusion

The evidence clearly demonstrates that diphenhydramine (Sleep-Eze) should not be used long-term for insomnia due to significant risks of cognitive impairment, falls, anticholinergic effects, and limited efficacy. The risks are particularly pronounced in older adults, who paradoxically represent a significant portion of users. Cognitive behavioral approaches offer safer and more effective long-term solutions for chronic insomnia.