Is diphenhydramine effective for treating allergies?

Is Diphenhydramine Effective for Allergies?

Yes, diphenhydramine is highly effective for treating allergic symptoms including runny nose, sneezing, itchy/watery eyes, and itching of the nose or throat, but second-generation antihistamines like fexofenadine, desloratadine, or loratadine are strongly preferred due to diphenhydramine's significant sedation and cognitive impairment. 1, 2

FDA-Approved Indications and Efficacy

• Diphenhydramine is FDA-approved to temporarily relieve symptoms due to hay fever or other respiratory allergies, including runny nose, sneezing, itchy/watery eyes, and itching of the nose or throat 1
• The medication is a histamine H1-receptor antagonist with proven efficacy in treating allergic reactions including anaphylaxis, urticaria, and allergic rhinitis 3, 4
• In a head-to-head trial, diphenhydramine 50 mg three times daily provided 77.6% reduction in nasal symptom scores compared to baseline (P < .001), significantly outperforming desloratadine which only achieved 21.0% reduction (P = .12) 5
• Diphenhydramine demonstrated clinically superior improvements across all individual allergy symptoms, including the notoriously difficult-to-treat nasal congestion 5

Critical Safety Concerns That Override Efficacy

Despite its superior efficacy, diphenhydramine should NOT be first-line therapy for allergic rhinitis due to substantial impairment risks. 2

Cognitive and Performance Impairment

• First-generation antihistamines like diphenhydramine cause significant sedation and impairment in school and driving performance 4
• Young adults with seasonal allergic rhinitis treated with diphenhydramine 50 mg performed significantly worse on learning tests compared to those treated with non-sedating antihistamines (P < .001) 6
• The impairment persists even after training periods, with examination performance remaining significantly worse in diphenhydramine-treated patients compared to controls (P < .001) 6
• Expert consensus strongly recommends against using older agents like diphenhydramine because they produce sedation, impairment, and worsen sleep architecture 2

Sedation Rates

• Somnolence occurred in 22.1% of patients taking diphenhydramine compared to only 4.5% with desloratadine and 3.4% with placebo 5
• The sedative effects are increased when combined with alcohol or other CNS depressants such as benzodiazepines or opioid narcotics 7, 4

Additional Adverse Effects

• Anticholinergic effects include hypotension, dizziness, blurred vision, dry mouth, epigastric discomfort, urinary retention, and wheezing 7, 4
• Paradoxical increase in rage and agitation can occur, particularly in children and adolescents 4
• Older adults face increased sensitivity and risk of side effects, including potential for delirium 4

Recommended Approach: Second-Generation Antihistamines First

Allergic rhinitis should be managed with relatively nonimpairing second-generation antihistamines (loratadine, desloratadine, cetirizine, or fexofenadine) as first-line therapy. 2

Onset of Action Comparison

• While diphenhydramine has historically been chosen for acute allergic reactions due to perceived faster onset, research shows this advantage is marginal 8
• In a randomized crossover study comparing oral fexofenadine 180 mg to oral and intramuscular diphenhydramine 50 mg, no significant differences were found in time to achieve 50% reduction in histamine-induced flares (P = .09) 8
• Diphenhydramine tended to work more rapidly than fexofenadine, but differences were not statistically significant 8
• Given the adverse effect profile of diphenhydramine with only marginal onset advantage, the risk-to-benefit ratio favors oral fexofenadine for acute urticarial or allergic reactions 8

When Diphenhydramine May Be Appropriate

Anaphylaxis (Second-Line Only)

• In anaphylaxis management, diphenhydramine 1-2 mg/kg or 25-50 mg parenterally is recommended as second-line therapy to epinephrine 7, 4
• H1 antihistamines should never be administered alone in the treatment of anaphylaxis 7
• Combination of diphenhydramine and ranitidine (H2 blocker) is superior to diphenhydramine alone, but both have much slower onset than epinephrine 7

Lidocaine Allergy Alternative

• For patients with true allergy to lidocaine, 1% diphenhydramine injection can serve as an alternative local anesthetic, though it has longer onset (5 minutes vs 1 minute for lidocaine) and limited efficacy 7

Procedural Sedation Adjunct

• As an adjunct to meperidine and midazolam during colonoscopy, diphenhydramine 50 mg improved overall sedation scores (9.4 vs 9.04, P = .017) and reduced requirements for meperidine (89.7 vs 100 mg, P = .003) and midazolam (3.4 vs 4.0 mg, P = .001) 7

Common Pitfalls to Avoid

• Never use diphenhydramine as first-line for routine allergic rhinitis when second-generation antihistamines are available and appropriate 2
• Never rely on diphenhydramine alone for anaphylaxis—epinephrine is the only first-line treatment 7
• Avoid in patients who need to drive, operate machinery, or perform cognitively demanding tasks due to significant impairment risk 2, 6
• Exercise caution in elderly patients due to increased risk of anticholinergic effects and delirium 4
• Monitor for paradoxical reactions in children and adolescents, which cannot be predicted unless previously documented 4