Level 1: Likely reliable evidence
Diphenhydramine (Benadryl) and desloratadine (Clarinex) were evaluated in a double-blind trial of 610 patients ages 12-65 years with moderate-to-severe seasonal allergic rhinitis (Ann Allergy Asthma Immunol. 2006;96:606-614). Participants were randomized to diphenhydramine 50 mg three times daily, desloratadine 5 mg once daily, or placebo for one week. A total of 589 patients (96.6%) completed the study.
Data were reported for 576 evaluable patients (94.4%), defined as baseline total symptom score ≥10, no significant protocol violations, and taking at least 80% of study medication; intention-to-treat analysis was reported to be similar, but data were not provided. The study was funded by Pfizer, which produces an antihistamine that competes with desloratadine; three of the four study authors work for Pfizer.
The symptoms of nasal congestion, runny nose, sneezing, and nasal itching were used to derive the 24-hour reflective total nasal symptom score (TNSS), based on a scale of 0-6 for each symptom. Baseline TNSS scores were 17.3 for diphenhydramine, 17.7 desloratadine, and 17.3 for placebo participants. Score reduction was -3.2 for participants receiving placebo compared with -3.88 for those receiving desloratadine (P = .12). The reduction in TNSS with diphenhydramine was -5.69 and significantly greater than with placebo (P <.001) or desloratadine (P <.001). Desloratadine significantly reduced sneezing, while diphenhydramine significantly reduced all four nasal symptoms.
An additional outcome, the 24-hour total symptom score (TSS), was derived from the TNSS plus four additional symptoms (itchy eyes, watering eyes, redness of eyes, and itching of ears or palate). At baseline, the TSS scores were 31.5 for diphenhydramine, 31.9 for desloratadine, and 31.9 for placebo participants. The reduction in TSS score was -6.61 for participants receiving placebo compared with -7.36 for those receiving desloratadine (P = .35). The reduction was -10.71 with diphenhydramine, which was significantly greater than with placebo (P <.001) or desloratadine (P <.001). Desloratadine did not significantly reduce any non-nasal symptoms whereas diphenhydramine significantly reduced all four non-nasal symptoms. Using intention-to-treat analysis, somnolence was reported by 3.4% of placebo patients, 4.5% of desloratadine patients, and 22.1% of diphenhydramine patients (NNH 5).