The randomized controlled trial by Merenstein et al1 demonstrating lack of an infant sleep response to diphenhydramine is a welcome addition to the pediatric literature. Old, first-generation H1 antihistamines such as diphenhydramine are widely used and are assumed to be effective and safe because they are available without prescription. However, these medications were introduced long before regulatory agencies mandated prospective, randomized, placebo-controlled, double-blind studies of the efficacy and safety of new chemical entities.2 The diphenhydramine dose recommended for infants and young children is based on anecdotal experience rather than on prospective pharmacokinetic and pharmacodynamic studies. The dose recommended for sleep is similar to the dose recommended for the treatment of allergic rhinitis or urticaria symptoms.
Simons FER. Diphenhydramine in Infants. Arch Pediatr Adolesc Med. 2007;161(1):105. doi:10.1001/archpedi.161.1.105-a