Objective: To critically review the body of clinical trials refuting or supporting the efficacy of topical antihistamines in the relief of pruritus.
Design: Review of PubMed from January 1950 through September 2009 and the Cochrane Database of Systematic Reviews to identify therapeutic trials of topical antihistamines in the relief of pruritus.
Main outcome measures: All randomized controlled trials or clinical trials of topical antihistaminic compounds used in the treatment of pruritus. The authors found 19 trials throughout the literature. The quality of each trial was ranked by applying a modified version of Sackett's criteria for clinical evidence. Grade A trials are large, randomized, double-blind, placebo-controlled studies with low false-positive (alpha) and low false-negative (beta) errors. Grade B studies are also randomized, double-blind, placebo-controlled studies, but include a small number of patients. Grade C trials lack one or more of the following criteria: randomization, placebo control or blinding.
Results: Only four large, randomized, double-blind, placebo-controlled clinical trials with definitive conclusions (grade A) support the use of topical antihistaminic agents, specifically topical doxepin, for relief of pruritus. Of seven grade B trials, four supported the efficacy of topical antihistamines while three refute their use in relieving pruritus. One grade B trial was inconclusive. All remaining trials (grade C) lacked placebo controls or randomization, or contained fewer than 20 patients in each treatment group.
Conclusion: While topical antihistamines are widely prescribed for the treatment of pruritus, the evidence to support their use is mixed. Topical doxepin has been demonstrated to reduce pruritus. Evidence is lacking, however, for other topical antihistamines, including diphenhydramine (Benadryl), that are widely used and available without a prescription.