Antihistamines for Viral Upper Respiratory Infections
Antihistamines are not recommended for routine treatment of the common cold or influenza-like illness in adults, as they provide only minimal short-term benefit (days 1-2) without clinically meaningful improvement in nasal symptoms, and may actually worsen congestion by drying nasal mucosa. 1, 2
Evidence Against Routine Use
The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2020) provides Level 1a evidence that antihistamines have limited effectiveness:
- Only days 1 and 2 show any benefit on overall symptom severity in adults, with no effect in the mid to long term 1
- No clinically significant effect on the cardinal symptoms of nasal obstruction, rhinorrhea, or sneezing 1
- The Cochrane systematic review confirms these findings: 45% of adults had beneficial effects with antihistamines versus 38% with placebo on days 1-2 (a modest 7% absolute difference), but this advantage disappears by days 3-4 3
Why Antihistamines Don't Work
The pathophysiology explains the lack of efficacy:
- Histamine is not responsible for cold symptoms - studies measuring inflammatory mediators during rhinovirus infections show histamine levels remain constant while kinins increase 10-fold, suggesting mast cells and basophils don't participate in viral URI pathophysiology 4
- Antihistamines may worsen congestion by drying nasal mucosa in patients without an allergic component 2, 5
When Combination Therapy May Be Considered
The only scenario where antihistamines show modest benefit is in combination products:
- Antihistamine-decongestant-analgesic combinations have some general benefit in adults and older children, though benefits must be weighed against adverse effects 1
- First-generation antihistamines (brompheniramine, diphenhydramine) combined with decongestants provide more rapid improvement in cough, throat clearing, and post-nasal drip compared to placebo 6
- Newer non-sedating antihistamines are ineffective for cold symptoms 7, 8
Special Populations to Avoid
Children under 6 years: The FDA recommends against over-the-counter cough and cold medications including antihistamines in this age group, with 54 documented fatalities between 1969-2006 5
Elderly patients: Should avoid antihistamines due to increased risk of adverse effects 2
Exception: Allergic Component Present
Antihistamines may be considered only when there is clear evidence of allergic rhinitis contributing to symptoms:
- Second-generation antihistamines are preferred in this scenario due to reduced sedation and anticholinergic effects 2
- This is treating the allergic component, not the viral infection itself 2, 6
What to Recommend Instead
For symptomatic relief of viral URI:
- Analgesics (acetaminophen, NSAIDs) for pain, fever, and headache 1, 6
- Nasal saline irrigation improves symptoms safely without medication risks 2, 5, 6
- Oral decongestants (pseudoephedrine/phenylephrine) for congestion unless contraindicated 6, 8
- Topical decongestants for short periods only (3-5 days maximum) to avoid rebound congestion 2, 6
Common Pitfall
Do not prescribe antihistamines as monotherapy for viral URI - the evidence shows no clinically meaningful benefit for nasal symptoms, only a marginal short-term effect on overall symptoms that doesn't justify routine use 1, 3