diphenhydramine

Adjunctive therapy

Brands: BENADRYL

Last reviewed 2026-02-12

Reviewed by PsychMed Editorial Team.

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Quick answers

What is diphenhydramine?
Diphenhydramine (brand Benadryl) is a first-generation antihistamine used over-the-counter (OTC) for allergy symptoms. It is also widely used as an OTC sleep aid and appears in many “PM” combination products.
What is BENADRYL?
BENADRYL is a brand name for diphenhydramine.
What is BENADRYL (diphenhydramine) used for?
Label indications include: Allergy symptoms (OTC labeling varies). Off-label use is common for insomnia and acute anxiety-related distress (practice pattern).
What drug class is BENADRYL (diphenhydramine)?
First-generation antihistamine (H1 antagonist) with sedating and anticholinergic effects; commonly used OTC for allergies and as a sleep aid.
What strengths does BENADRYL (diphenhydramine) come in?
Common OTC tablets/capsules are 25 mg (product-dependent).

Snapshot

Primary label indications include: Allergy symptoms (OTC labeling varies).
Class: Adjunctive therapy
Common US brands: BENADRYL
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2026-02-12

Label indications

Allergy symptoms (OTC labeling varies). Off-label use is common for insomnia and acute anxiety-related distress (practice pattern).

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Clinical Highlights

Diphenhydramine (brand Benadryl) is a first-generation antihistamine used over-the-counter (OTC) for allergy symptoms. It is also widely used as an OTC sleep aid and appears in many “PM” combination products. Sedation is expected and often the main reason people take it for sleep, but diphenhydramine is also strongly Anticholinergic—so confusion, constipation, urinary retention, and blurred vision can be clinically significant, especially in older adults or with polypharmacy (Beers/clinical).

Evidence for chronic insomnia benefit is limited. The AASM guideline recommends against routine diphenhydramine use for chronic insomnia (weak recommendation), so treat it as a time-limited, symptom-focused adjunct while addressing underlying drivers (mood, substances, pain, sleep apnea, circadian disruption).
Next-day impairment is a key limiter: falls, driving impairment, and daytime cognitive slowing can occur, particularly with higher doses, alcohol co-use, or other sedatives (clinical).
Best fit is usually short-term, situational insomnia when a sedating OTC option is preferred and anticholinergic risk is low—not a default long-term sleep strategy.
The compare view, diphenhydramine evidence feed, and diphenhydramine print page can help weigh OTC options against evidence-backed insomnia medications.

Dosing & Formulations

Common OTC tablets/capsules are 25 mg. Label dosing for allergy symptoms varies by product; one common pattern is 25–50 mg every 4–6 hours with a daily maximum (label varies). As a sleep aid, OTC products are commonly taken as a single bedtime dose (often 25–50 mg). Start with the lowest effective dose and avoid escalating when next-day impairment appears (clinical).

Avoid combining multiple “PM” products (e.g., acetaminophen PM plus a separate sleep aid) because duplicate diphenhydramine exposure can be easy to miss.
If insomnia persists, avoid open-ended nightly use; reassess for treatable drivers and consider CBT-I and evidence-based options rather than stacking sedatives.

Monitoring & Risks

Sedation and impaired coordination: counsel about driving, machinery, and falls; effects can persist into the next day (clinical). Anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision): higher risk in older adults and those with urinary obstruction or glaucoma (Beers/clinical).

Cognitive effects: confusion, delirium, and worsened memory can occur, especially in older adults and in serious mental illness where baseline cognitive vulnerability may already be present (Beers/clinical).
Overdose risk: anticholinergic toxicity, seizures, and arrhythmias can occur with large ingestions; keep away from children and avoid “dose chasing” for sleep (clinical).

Drug Interactions

Additive CNS/respiratory depression occurs with alcohol, opioids, benzodiazepines, sedating antipsychotics, and other hypnotics; avoid stacking sedatives when possible. Additive anticholinergic burden with other anticholinergics (e.g., low-potency antipsychotics, bladder antimuscarinics, tricyclics) increases delirium and urinary retention risk (clinical).

Diphenhydramine is metabolized largely by CYP2D6 and can interact with CYP2D6-modulating medications; if side effects increase after medication changes, reassess the full regimen (StatPearls/clinical).

Practice Notes

Avoid chronic nightly diphenhydramine use in older adults when possible (Beers). If insomnia is persistent, prioritize CBT-I and treat comorbid contributors rather than escalating OTC sedatives. If a sedating PRN is being used for acute anxiety or agitation, compare diphenhydramine with alternatives and monitor for anticholinergic delirium, especially in medically ill or older patients.

If next-day impairment is prominent, switch agents rather than increasing dose or adding additional sedatives to “counter” side effects.
For ongoing insomnia, consider evidence-backed options (e.g., DORAs, ramelteon, low-dose doxepin) and reassess sleep apnea, substance use, and mood symptoms.

References

Benadryl (diphenhydramine) tablets (OTC) label — DailyMed (2026)
Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline — Journal of Clinical Sleep Medicine (2017)
2023 American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults — Journal of the American Geriatrics Society (2023)
Diphenhydramine (StatPearls) — StatPearls Publishing (NCBI Bookshelf) (2025)