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The TIRED Study—A Randomized, Controlled, Patient-Oriented Trial

Dan Merenstein, MD; Marie Diener-West, PhD; Ann C. Halbower, MD; Alex Krist, MD; Haya R. Rubin, MD, PhD

Arch Pediatr Adolesc Med. 2006;160:707-712.

Objective  To determine if infants aged 6 to 15 months with frequent parent-reported nighttime awakenings require reduced parental aid during a week of diphenhydramine hydrochloride treatment and 2 and 4 weeks after its discontinuation.

Design  Double-blind, randomized, controlled clinical trial.

Setting  The study was conducted from May 1, 2004, through May 1, 2005; patients were recruited nationally.

Participants  Forty-four participants aged 6 to 15 months.

Interventions  Placebo or diphenhydramine was administered in infants 30 minutes before anticipated bedtime.

Main Outcome Measures  The primary outcome was dichotomous: a parental report of improvement in the number of night awakenings requiring parental assistance during the intervention week, which ended on day 14. Secondary outcomes were improved sleep during the 2 weeks before days 29 and 43, parental overall happiness with sleep, and improved sleep latency.

Results  On June 6, 2005, the data safety monitoring board voted unanimously to stop the trial early because of lack of effectiveness of diphenhydramine over placebo. Only 1 of 22 children receiving diphenhydramine showed improvement compared with 3 of 22 receiving placebo. To reach the a priori determined sample size and have a positive outcome (ie, rejecting the null hypothesis), the trial would have needed to enroll 16 more participants in each arm, with 15 of the 16 in the diphenhydramine group and 0 of 16 in the placebo group improving.

Conclusion  During 1 week of therapy and at follow-up 2 and 4 weeks later, diphenhydramine was no more effective than placebo in reducing nighttime awakening or improving overall parental happiness with sleep for infants.

Author Affiliations: Robert Wood Johnson Clinical Scholars Program (Drs Merenstein and Diener-West) and Department of Pediatrics (Dr Halbower), The Johns Hopkins University School of Medicine, and Departments of Biostatistics and Epidemiology, The Johns Hopkins Bloomberg School of Public Health (Dr Diener-West), Baltimore, Md; Department of Family Medicine, Fairfax Family Practice Residency, Virginia Commonwealth University, Richmond (Dr Krist); and Department of Medicine and Healthcare Services and Quality Research Program, John A. Burns School of Medicine, University of Hawaii, Honolulu (Dr Rubin). Dr Merenstein is now with the Department of Family Medicine, Georgetown University, Washington, DC.

RELATED LETTERS

Diphenhydramine in Infants
F. Estelle R. Simons
Arch Pediatr Adolesc Med. 2007;161(1):105.
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Diphenhydramine in Infants—Reply
Dan Merenstein, Marie Diener-West, Ann C. Halbower, Alex Krist, and Haya R. Rubin
Arch Pediatr Adolesc Med. 2007;161(1):105.
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