What is the effect of using antihistamines to treat the common cold?

Antihistamines for the Common Cold: Limited and Clinically Insignificant Benefit

Antihistamines provide only minimal short-term benefit for common cold symptoms in adults (days 1-2 only), with no clinically significant effect on the key nasal symptoms of congestion, runny nose, or sneezing, and they are not effective in children. 1

Evidence Quality and Strength

The most recent and highest-quality evidence comes from the 2020 European Position Paper on Rhinosinusitis, which provides Level 1a evidence (systematic review of randomized controlled trials) specifically addressing antihistamine use in the common cold 1. This guideline supersedes older recommendations and provides the clearest guidance.

Specific Effects on Symptoms

Overall Symptom Severity

• Short-term only: Antihistamines show a limited beneficial effect on overall symptom severity during days 1 and 2 of treatment in adults 1
• No mid to long-term benefit: This effect disappears after the first two days, with no sustained improvement 1, 2
• In practical terms, 45% of adults experience benefit with antihistamines versus 38% with placebo on days 1-2, representing a modest 7% absolute difference 2

Individual Nasal Symptoms

• Nasal obstruction: No clinically significant effect 1, 2
• Rhinorrhea (runny nose): No clinically significant effect despite some statistical differences 1, 2
• Sneezing: No clinically significant effect 1, 2

The key distinction here is that while first-generation antihistamines may show statistically significant reductions in rhinorrhea and sneezing, these differences are not clinically meaningful in real-world practice 2.

Critical Distinction: First-Generation vs. Second-Generation Antihistamines

First-Generation (Sedating) Antihistamines

• These work primarily through anticholinergic properties, not antihistamine effects, since histamine plays minimal role in common cold pathophysiology 1
• Examples include diphenhydramine, brompheniramine, doxylamine, and chlorpheniramine 1, 3
• May provide modest benefit for cough associated with post-nasal drip from viral upper respiratory infections 1

Second-Generation (Non-Sedating) Antihistamines

• Completely ineffective for common cold symptoms 1
• Studies with terfenadine, loratadine, and other newer antihistamines consistently show no benefit 1
• Should not be used for common cold treatment 1

Pediatric Considerations: Do Not Use

Antihistamines should not be used in children under 6 years of age for common cold symptoms due to lack of efficacy and significant safety concerns. 1, 4

Safety Data

• Between 1969-2006, there were 69 fatalities associated with antihistamines in children ≤6 years, with 41 deaths in children under 2 years 1, 4
• Common causes included drug overdose, medication errors, and use of multiple products 1, 4
• The FDA's Nonprescription Drugs and Pediatric Advisory Committees recommended against OTC cough and cold medications in children under 6 years 1, 4

Efficacy in Children

• Controlled trials show antihistamine-decongestant combinations are not effective for upper respiratory infection symptoms in children 1
• No evidence supports antihistamine monotherapy in pediatric populations 2
• One study showed diphenhydramine was no different than placebo for nocturnal cough or sleep disturbance in children 1

Side Effects Profile

Common Adverse Effects

• Sedation: Most common side effect with first-generation antihistamines, though one meta-analysis questions whether sedation is significantly greater than with newer agents 1
• Anticholinergic effects: Dry mouth, transient dizziness 1
• Urinary retention: Particularly in older men with prostatic hypertrophy 1

Important Safety Note

Overall, the incidence of adverse effects is not statistically significantly higher than placebo in most trials, though sedation is more commonly reported 1, 2.

Clinical Algorithm for Decision-Making

Step 1: Determine if this is truly a common cold or allergic rhinitis

• If allergic component present: Use second-generation antihistamines 1
• If pure viral common cold: Antihistamines are not recommended 1

Step 2: If patient insists on symptomatic treatment for common cold:

• First choice: Decongestants (oral or nasal) for nasal congestion 1
• For pain/headache: NSAIDs or acetaminophen 1
• For rhinorrhea specifically: Ipratropium bromide nasal spray is more effective than antihistamines 1

Step 3: If considering antihistamine-decongestant combinations:

• May have some general benefit in adults and older children (>12 years) 1
• Weigh benefits against sedation and other side effects 1
• Never use in children under 6 years 1, 4

Step 4: If patient has persistent cough with post-nasal drip:

• Consider first-generation antihistamine plus decongestant (e.g., brompheniramine 6 mg + pseudoephedrine 120 mg twice daily) 1
• This works through anticholinergic effects, not antihistamine action 1
• Start once daily at bedtime to minimize sedation, then advance to twice daily if tolerated 1

Common Pitfalls to Avoid

1. Do not prescribe second-generation antihistamines (loratadine, cetirizine, fexofenadine) for common cold—they are ineffective 1

2. Do not use antihistamines as monotherapy expecting significant nasal symptom relief—the evidence does not support this 1, 2

3. Do not recommend antihistamines for children under 6 years—risk outweighs any potential benefit 1, 4

4. Do not confuse allergic rhinitis with common cold—treatment approaches differ significantly 1

5. Avoid topical decongestants beyond 3 days due to risk of rhinitis medicamentosa 1

Better Alternatives for Common Cold

• Nasal saline irrigation: Possible benefits, especially in children, with minimal side effects 1
• Oral/nasal decongestants: Small positive effect on nasal congestion in adults 1
• NSAIDs: Effective for headache, ear pain, muscle/joint pain, and may improve sneezing 1
• Ipratropium bromide nasal spray: Effective for rhinorrhea specifically 1
• Vitamin C: May be worthwhile for individual patients to trial given low cost and safety 1