Clinical question
Does diphenhydramine promote sleep in infants whose parents report frequent nocturnal awakenings?

Bottom line
Diphenhydramine was no more effective (and was technically less effective) than placebo in reducing parental attention in infants with frequent nocturnal awakenings. (LOE = 2b)

Reference
Merenstein D, Diener-West M, Halbower AC, Krist A, Rubin HR. The trial of infant response to diphenhydramine: the TIRED study--A randomized, controlled, patient-oriented trial. Arch Pediatr Adolesc Med 2006;160:707-712.

Study design: Randomized controlled trial (double-blinded)

Funding: Foundation

Allocation: Concealed

Setting: Outpatient (primary care)

Synopsis
Children aged 6 months to 15 months whose parents reported at least 2 nocturnal awakenings were randomized to receive 1 week of diphenhydramine (1 mg/kg) or placebo 30 minutes before anticipated bedtime. The main outcome was whether the child required parental attention during the night. The study design called for 38 patients in each group. However, after 44 patients completed the study, an independent data monitoring committee unanimously voted to stop the study early because of the dismal results: 1 of 22 children receiving diphenhydramine showed improvement compared with 3 of 22 infants taking placebo.