The trial of infant response to diphenhydramine: the TIRED study--a randomized, controlled, patient-oriented trial
Dan Merenstein1, Marie Diener-West, Ann C Halbower
1Robert Wood Johnson Clinical Scholars Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. djm23@georgetown.edu
Insights
Diphenhydramine hydrochloride did not prove more effective than placebo for reducing nighttime awakenings in infants aged 6 to 15 months. This study found no significant improvement in infant sleep or parental satisfaction with the medication.
Area of Science:
- Pediatric Sleep Medicine
- Clinical Pharmacology
Background:
- Frequent nighttime awakenings are a common concern for parents of infants.
- Diphenhydramine hydrochloride is a common antihistamine sometimes used off-label for infant sleep issues.
Purpose of the Study:
- To evaluate the efficacy of diphenhydramine hydrochloride in reducing parental-reported nighttime awakenings in infants aged 6 to 15 months.
- To assess the impact on parental satisfaction and sleep latency.
Main Methods:
- A double-blind, randomized, placebo-controlled clinical trial.
- Forty-four infants (6-15 months) received either diphenhydramine hydrochloride or placebo before bedtime.
- Outcomes measured included parental reports of nighttime awakenings, overall sleep satisfaction, and sleep latency.
Main Results:
- The trial was stopped early due to lack of effectiveness; diphenhydramine was not superior to placebo.
- Only 1 of 22 infants on diphenhydramine improved compared to 3 of 22 on placebo.
- The study lacked statistical power to confirm efficacy, requiring significantly more participants with a high improvement rate in the diphenhydramine group.
Conclusions:
- Diphenhydramine hydrochloride demonstrated no significant benefit over placebo in reducing infant nighttime awakenings.
- No improvements were observed in parental sleep satisfaction or sleep latency during treatment or follow-up periods.
- The findings do not support the use of diphenhydramine hydrochloride for managing frequent nighttime awakenings in infants.
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.
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