The trial of infant response to diphenhydramine: the TIRED study--a randomized, controlled, patient-oriented trial.

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.