Which medication can be used to treat upper‑respiratory infection symptoms and also manage antipsychotic‑induced tremor?

Diphenhydramine for URI Symptoms and Antipsychotic-Induced Tremor

Diphenhydramine is the medication that can treat both upper respiratory infection symptoms and antipsychotic-induced tremor, serving dual purposes through its antihistaminic and anticholinergic properties. 1

Mechanism of Dual Action

• Diphenhydramine works for URI symptoms primarily through its anticholinergic properties rather than antihistamine effects, reducing nasal secretions and suppressing inflammatory mediators that trigger cough 1, 2
• For antipsychotic-induced tremor (extrapyramidal symptoms), diphenhydramine's anticholinergic activity counteracts the dopamine blockade that causes the movement disorder 1
• The anticholinergic mechanism explains why diphenhydramine addresses both conditions simultaneously, unlike second-generation antihistamines that lack these properties 1, 2

Dosing Recommendations

For URI Symptoms (Adult)

• Diphenhydramine 25-50 mg every 4-6 hours, maximum 6 doses per 24 hours 2
• For children ≥2 years: 12.5 mg/5 mL formulation 2
• Combination with sustained-release pseudoephedrine 120 mg twice daily provides superior efficacy for URI symptoms compared to diphenhydramine alone 1, 2

For Antipsychotic-Induced Tremor

• Diphenhydramine is used in combination with antipsychotics (e.g., haloperidol + diphenhydramine or risperidone + diphenhydramine) to prevent or treat extrapyramidal symptoms including tremor 1
• The pediatric guideline specifically lists these combinations as standard chemical restraint protocols, indicating established efficacy for managing antipsychotic side effects 1

Clinical Algorithm for Use

When both conditions are present:

1. Start diphenhydramine 25-50 mg every 4-6 hours for adults 2
2. Add sustained-release pseudoephedrine 120 mg twice daily if nasal congestion is prominent and no contraindications exist 2
3. Expect URI symptom improvement within days to 2 weeks 1, 2
4. Monitor for tremor reduction within hours to days of initiating therapy 1

Contraindications to screen before prescribing:

• Narrow-angle glaucoma (absolute contraindication) 2
• Symptomatic benign prostatic hypertrophy or urinary retention (absolute contraindication) 2
• Severe uncontrolled hypertension (contraindication to pseudoephedrine component) 2
• Congestive heart failure (contraindication to pseudoephedrine component) 2

Important Caveats

• Sedation occurs in 13-14% of patients taking first-generation antihistamines versus 1.5% with placebo; starting with bedtime dosing for several days before advancing to daytime doses can mitigate this effect 2
• The sedative property may actually provide additional benefit for nocturnal cough associated with URI 2
• Diphenhydramine can cause QTc prolongation, particularly when combined with antipsychotics that also prolong QTc interval; monitor with electrocardiogram when feasible in patients receiving both medications 1
• Performance impairment can occur even without subjective awareness of sedation, affecting driving and work performance 2
• Older adults are at higher risk for anticholinergic side effects including confusion, urinary retention, and falls 2

What NOT to Use

• Second-generation antihistamines (cetirizine, loratadine, fexofenadine) are ineffective for URI-related cough because they lack anticholinergic properties and do not treat antipsychotic-induced tremor 1, 2
• Newer antihistamines with or without decongestants have been proven ineffective in multiple randomized trials for URI symptoms 1
• Antibiotics have no role in viral URI and should not be prescribed during the first week of symptoms 1, 2

Monitoring Parameters

• Blood pressure if pseudoephedrine is added (risk of hypertension, tachycardia, palpitations) 2
• Anticholinergic side effects: dry mouth, constipation, urinary retention, blurred vision 1, 2
• Cardiac monitoring with pulse oximetry and/or electrocardiogram when combining with antipsychotics due to additive QTc prolongation risk 1
• Tremor severity and frequency to assess therapeutic response 1