First-Generation Antihistamine for Chronic Cough
For chronic cough in adults, use a first-generation antihistamine combined with a decongestant: specifically dexbrompheniramine 6 mg plus pseudoephedrine 120 mg (sustained-release) twice daily, or alternatively brompheniramine 12 mg plus pseudoephedrine 120 mg twice daily. 1
Evidence-Based First-Line Options
The American College of Chest Physicians guidelines establish first-generation antihistamine/decongestant combinations as the standard empiric treatment for Upper Airway Cough Syndrome (UACS), the most common cause of chronic cough in adults. 2, 1 The specific combinations proven effective in controlled trials are:
Preferred regimens:
- Dexbrompheniramine 6 mg + pseudoephedrine 120 mg (sustained-release) twice daily 2, 1
- Azatadine 1 mg + pseudoephedrine 120 mg (sustained-release) twice daily 2, 1
- Brompheniramine 12 mg + pseudoephedrine 120 mg twice daily 1
Alternative monotherapy options (if decongestants contraindicated):
- Chlorpheniramine 4 mg four times daily 1, 3
- Diphenhydramine 25-50 mg four times daily 1, 4
- Hydroxyzine 25 mg four times daily 1
Why First-Generation Antihistamines Work
The mechanism is anticholinergic activity, not antihistamine effects. 1, 5 First-generation antihistamines reduce nasal secretions and limit inflammatory mediators that trigger the cough reflex through their anticholinergic properties. 1, 6 This explains why second-generation antihistamines (cetirizine, loratadine, fexofenadine) are completely ineffective for UACS—they lack anticholinergic activity. 2, 1, 5
Dosing Strategy to Minimize Sedation
Start with once-daily dosing at bedtime for several days, then advance to twice-daily dosing. 1, 6 This approach minimizes daytime sedation, the primary side effect of first-generation antihistamines. 1, 7 Improvement typically occurs within days to 2 weeks of starting treatment. 1, 8, 6
When to Proceed with Further Evaluation
If no response after 2 weeks of adequate first-generation antihistamine/decongestant therapy:
- Obtain sinus imaging (CT or radiographs) to evaluate for chronic sinusitis 2, 1
- Consider asthma/non-asthmatic eosinophilic bronchitis as alternative diagnosis 2, 8
- Initiate empiric proton pump inhibitor therapy (omeprazole 20-40 mg twice daily before meals for at least 8 weeks) for possible GERD 8, 6
Multiple causes often coexist—UACS, asthma, and GERD together account for approximately 90% of chronic cough cases. 8 Maintain all partially effective treatments rather than discontinuing them prematurely. 8
Critical Contraindications and Monitoring
Absolute contraindications:
Monitor for:
- Blood pressure elevation (from decongestant component) 8, 6
- Anticholinergic effects: dry mouth, constipation, urinary retention, increased intraocular pressure 1, 6
- Performance impairment (can occur without subjective awareness of sedation) 1, 9
For patients with hypertension or cardiovascular contraindications to decongestants:
- Use intranasal corticosteroids (fluticasone 100-200 mcg daily) as first-line instead 8, 6
- Add ipratropium bromide nasal spray (42 mcg per spray, 2 sprays per nostril 4 times daily) for anticholinergic drying without systemic effects 8, 6
Common Pitfall: Using Second-Generation Antihistamines
Never use second-generation antihistamines (cetirizine, loratadine, fexofenadine) for chronic cough due to UACS. 2, 1, 6 Multiple studies confirm they are ineffective because they lack the anticholinergic properties necessary to reduce secretions and suppress cough. 2, 1, 5 This is a Grade D recommendation (evidence of no benefit) from the American College of Chest Physicians. 2
Special Consideration: "Silent" UACS
Approximately 20% of patients have no obvious postnasal drip symptoms yet still respond to first-generation antihistamine/decongestant therapy. 8 Therefore, empiric treatment is justified even without classic symptoms of throat clearing, nasal discharge, or cobblestoning of the posterior pharynx. 2, 1