What to do for a patient with an itchy throat and dry cough unresponsive to antitussives (cough suppressants) and antihistamines?

Evaluation and Management of Refractory Itchy Throat and Dry Cough

Immediate Next Step: Empiric Trial of First-Generation Antihistamine/Decongestant Combination

If antitussives and antihistamines have failed, the most likely diagnosis is Upper Airway Cough Syndrome (UACS), and you should immediately initiate a first-generation antihistamine combined with a decongestant—specifically dexbrompheniramine 6 mg plus pseudoephedrine 120 mg (sustained-release) twice daily or brompheniramine 12 mg plus pseudoephedrine 120 mg (sustained-release) twice daily. 1, 2

Critical Clarification on "Antihistamines"

The failure you're describing likely involves second-generation antihistamines (cetirizine, loratadine, fexofenadine), which are completely ineffective for UACS-related cough. 1, 2 First-generation antihistamines work through their anticholinergic properties, not antihistamine effects, which is why they succeed where newer agents fail. 1, 3

Treatment Algorithm

Step 1: Initiate First-Generation Antihistamine/Decongestant (Days 1-14)

• Start with dexbrompheniramine 6 mg + pseudoephedrine 120 mg (sustained-release) twice daily OR azatadine 1 mg + pseudoephedrine 120 mg (sustained-release) twice daily 1, 2
• Dosing strategy to minimize sedation: Begin with once-daily dosing at bedtime for 3-5 days, then advance to twice-daily dosing (morning and bedtime) 1, 2
• Expected timeline: Improvement typically occurs within days to 2 weeks 1, 3

Contraindications to check before prescribing: 2

• Symptomatic benign prostatic hypertrophy or urinary retention (absolute contraindication)
• Narrow-angle glaucoma (absolute contraindication)
• Cognitive impairment, especially in older adults (absolute contraindication)
• Monitor blood pressure in hypertensive patients 3, 2

Step 2: Add Intranasal Corticosteroids if No Response After 1-2 Weeks

• Add fluticasone 100-200 mcg daily for a 1-month trial if the antihistamine/decongestant combination alone is insufficient 3
• Intranasal corticosteroids are effective for both allergic and non-allergic rhinitis-related UACS 3

Step 3: Consider Alternative Anticholinergic Agent for Contraindications

• If decongestants are contraindicated, use ipratropium bromide nasal spray (42 mcg per spray, 2 sprays per nostril 4 times daily) to provide anticholinergic drying effects without systemic cardiovascular side effects 3

Step 4: Evaluate for Other Common Causes if No Response After 2 Weeks

If symptoms persist despite adequate upper airway treatment for 2 weeks, proceed with sequential evaluation: 1, 3

A. Asthma/Non-Asthmatic Eosinophilic Bronchitis

• Consider bronchial provocation testing if spirometry is normal 3
• Trial of inhaled corticosteroids with bronchodilators 4

B. Gastroesophageal Reflux Disease (GERD)

• Initiate empiric therapy with omeprazole 20-40 mg twice daily before meals for at least 8 weeks plus dietary modifications 3
• Critical caveat: Improvement in cough from GERD treatment may take up to 3 months 3
• GERD frequently mimics UACS with upper respiratory symptoms 3

C. Pertussis (Whooping Cough)

• Consider in patients with prolonged cough (>2 weeks) with paroxysms 5
• Order nasopharyngeal culture for definitive diagnosis 5
• If confirmed or probable: Macrolide antibiotic and isolate for 5 days from start of treatment 5
• Important timing: Early treatment within first few weeks diminishes coughing paroxysms; treatment beyond this period unlikely to help 5

Step 5: Obtain Sinus Imaging if Persistent After Initial Treatment

• Order sinus CT or radiographs if symptoms persist despite 2 weeks of adequate topical therapy 3
• Air-fluid levels indicate acute bacterial sinusitis requiring antibiotics 3
• Chronic sinusitis may present with relatively or completely nonproductive cough 2

Critical Pitfalls to Avoid

Common Mistake #1: Using Second-Generation Antihistamines

• Never use cetirizine, loratadine, fexofenadine, or desloratadine for UACS—they are ineffective regardless of whether combined with decongestants 1, 2

Common Mistake #2: Missing "Silent" UACS

• Approximately 20% of patients have no obvious postnasal drip symptoms yet still respond to UACS-directed treatment 3
• Absence of typical findings (postnasal drainage, cobblestoning, throat clearing) does not rule out UACS 3

Common Mistake #3: Premature Discontinuation of Partially Effective Treatments

• Maintain all partially effective treatments rather than discontinuing them prematurely, as UACS, asthma, and GERD together account for approximately 90% of chronic cough cases 3

Common Mistake #4: Using Phenylephrine Instead of Pseudoephedrine

• The evidence specifically supports pseudoephedrine-containing combinations, not phenylephrine 1, 2

Common Mistake #5: Expecting Rapid Response from All Treatments

• UACS treatment: days to 2 weeks 1
• GERD treatment: up to 3 months 3
• Complete resolution of UACS may take several weeks to a few months 3

Adjunctive Symptomatic Therapy

• For symptomatic cough relief while treating underlying cause: Consider dextromethorphan as an over-the-counter cough suppressant 3
• High-volume saline nasal irrigation (150 mL) improves outcomes through mechanical removal of mucus and enhanced ciliary activity—more effective than saline spray 3

When to Consider Referral

• If no response after systematic evaluation and treatment of UACS, asthma/NAEB, and GERD 3
• Consider multimodality speech pathology therapy for unexplained chronic cough 3
• Gabapentin can be considered for unexplained chronic cough with careful risk-benefit discussion, starting at 300 mg once daily 3