Extended Use of Diphenhydramine (Benadryl) for 4 Months
Diphenhydramine should not be used for 4 months or any extended period for sleep or chronic conditions, as it is not recommended for long-term use and lacks established efficacy for chronic insomnia. 1
Evidence Against Long-Term Use
The American Academy of Sleep Medicine explicitly states that diphenhydramine is not recommended for treating either sleep onset or sleep maintenance insomnia based on systematic review of the evidence 1. The data shows:
- Mean improvement in total sleep time was only 12 minutes compared to placebo (with confidence intervals ranging from 13 minutes worse to 38 minutes better) 1
- No improvement in quality of sleep compared to placebo 1
- Mean reduction in sleep latency was only 8 minutes 1
OTC sleep medications containing antihistamines have not established efficacy for insomnia treatment, especially for long-term use 1. This represents a consensus position from sleep medicine guidelines dating back over a decade that remains current.
Specific Risks of Extended Use
Tolerance and Diminishing Efficacy
The hypnotic effect of diphenhydramine is significantly reduced in patients who have received previous treatment, demonstrating rapid tolerance development 2. A 2-week study in psychiatric patients showed effectiveness only in treatment-naive individuals, with dose-dependent effects lost in those previously treated 2.
Anticholinergic Burden
Extended use poses particular risks in older adults, where diphenhydramine is classified as potentially inappropriate medication by the 2015 Beers Criteria 3. More than half of older adults using OTC sleep aids are taking diphenhydramine or doxylamine despite these recommendations 3.
Safety Profile Concerns
Recent expert consensus emphasizes that it is definitively time to move on from diphenhydramine due to negative side effects including sedation, cardiac toxicity risk in overdose, and wide availability of safer alternatives 4. Second-generation antihistamines offer the same desired effects with fewer undesirable side effects 4.
Recommended Alternatives
For chronic insomnia requiring pharmacotherapy beyond 4 months, the following FDA-approved options have demonstrated efficacy without short-term usage restrictions:
- Eszopiclone (2-3 mg): Mean 28-57 minute improvement in total sleep time with moderate-to-large improvement in sleep quality 1
- Suvorexant: Mean 10 minute improvement in total sleep time with 16-28 minute reduction in wake after sleep onset 1
- Doxepin (3-6 mg): Mean 29 minute improvement in total sleep time with small-to-moderate improvement in sleep quality 1
These agents have been studied for extended use and do not carry the same restrictions as diphenhydramine 1.
Clinical Pitfalls to Avoid
Do not prescribe diphenhydramine "just in case" for ongoing symptoms 1. This principle from pain management guidelines applies equally to sleep medications - reassess the underlying condition rather than continuing ineffective treatment.
Avoid assuming OTC status equals safety for chronic use 3. Many patients and providers incorrectly believe that over-the-counter availability indicates appropriateness for long-term use, when evidence shows the opposite 1.
Screen for underlying sleep disorders before any pharmacotherapy. The lack of efficacy data for diphenhydramine in chronic insomnia suggests that continued use likely indicates an unaddressed underlying condition requiring proper evaluation 1.