Generic Name

Unisom

Mechanism

• H1‑histamine receptor antagonist: blocks central peripheral H1 receptors, yielding a sedating effect.
• Anticholinergic activity: inhibits muscarinic receptors → dry mouth, urinary retention, and blurred vision.
• GABA‑ergic modulation: diphenhydramine enhances GABA transmission indirectly, contributing to CNS depression.
• The sedative effect peaks 30–60 min after oral intake and is most pronounced with 25–50 mg dosing.

Pharmacokinetics

Indications

• Short‑term insomnia (≤4–6 weeks) caused by occasional sleeplessness or jet‑lag.
• OTC use for “just‑in‑time” sleep induction when other non‑pharmacologic strategies fail.

Contraindications

• Known hypersensitivity to diphenhydramine or related compounds.
• Severe hepatic or renal impairment (extended half‑life).
• Prostatic hypertrophy, chronic obstructive pulmonary disease, narrow‑angle glaucoma, or severe cardiac conduction abnormalities (risks of anticholinergic effects).
• Pregnancy: Category C; use only if benefits outweigh risks, preferably after the first trimester.
• Lactation: drug is excreted into breast milk → not recommended.

Warnings
• Cognitive/neurologic impairment: risk of falls, especially in elderly.
• Anticholinergic toxicity: delirium, urinary retention, tachycardia, constipation.
• Interaction with CNS depressants (e.g., alcohol, benzodiazepines, opioids) → additive sedation.

Dosing

• Adults (≥18 y): 25–50 mg orally 30–60 min before bedtime.
• Children: Not approved; caution advised in pediatric practice.
• Maximum duration: Do not exceed 4–6 weeks of continuous use.
• Titration: Start at 25 mg; increase to 50 mg if inadequate sedation (after ≥2 weeks).
• Special populations:
• *Elderly*: begin with 25 mg; monitor for anticholinergic side‑effects.
• *Renal/hepatic impairment*: dose reduction or extended dosing interval is prudent.

Adverse Effects

• Common
• Drowsiness, somnolence, fatigue
• Dry mouth, blurred vision
• Dizziness, light‑headedness
• Constipation, urinary retention
• Mild GI upset (nausea, cramping)
• Serious (rare)
• Anticholinergic syndrome (delirium, tachycardia, hyperthermia)
• Hypersensitivity reactions (rash, angioedema)
• Severe CNS depression → respiratory compromise (in overdose)
• Acute angle‑closure glaucoma (in susceptible individuals)

Monitoring

• Baseline: Mental status (confusion, agitation), hepatic/renal labs, cardiovascular assessment in high‑risk patients.
• During therapy:
• Fall risk assessment in elderly
• Periodic liver enzyme and renal function tests if prolonged use
• Monitor for signs of anticholinergic toxicity (dry eye/mouth, blurred vision, urinary retention).
• When co‑prescribed: Check for additive CNS depression (e.g., with opioids, benzodiazepines).

Clinical Pearls

• Tolerance develops quickly: after 2–3 days the hypnotic effect diminishes; hence limited to short‑term use.
• Avoid in patients on antihypertensive or antiarrhythmic meds—diphenhydramine can potentiate bradycardia and hypotension.
• Use before activities requiring alertness: schedule bedtime at least 2–3 h before tomorrow’s responsibilities.
• Elderly patients: prefer alternatives with a better safety profile (e.g., low‑dose trazodone, doxylamine succinate).
• Combination with OTC cold: many cold preparations contain diphenhydramine; check label to avoid accidental overdose.
• Driving after use: the sedative effect can linger next morning; advise patients to steer clear of driving or operating heavy machinery the day after taking Unisom.

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• Key Takeaway: *Unisom* (diphenhydramine) is a convenient, low‑cost OTC hypnotic suitable for brief episodes of insomnia. Its first‑generation antihistamine profile provides efficacy but carries anticholinergic and CNS depressant risks, especially in the elderly, therefore it should be used cautiously and for the shortest effective duration.