Next-day residual sedative effect after nighttime administration of an over-the-counter antihistamine sleep aid, diphenhydramine, measured by positron emission tomography

Dongying Zhang, Manabu Tashiro, Katsuhiko Shibuya, Nobuyuki Okamura, Yoshihito Funaki, Takeo Yoshikawa, Masato Kato, Kazuhiko Yanai

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Antihistamines often are self-administered at night as over-the-counter (OTC) sleep aids, but their next-day residual sedative effect has never been evaluated using a reliable quantitative method such as positron emission tomography (PET). We performed a double-blind, placebo-controlled, crossover study in which we evaluated the residual effect the next day after nighttime administration of diphenhydramine, a commonly used OTC sleep aid, in terms of brain H1 receptor occupancy (H1RO) measured using 11C-doxepin-PET. We also compared the results of diphenhydramine with those of bepotastine, a second-generation antihistamine. Eight healthy adult male subjects underwent PET measurement the morning (11:00) after random oral administration of diphenhydramine (50 mg), bepotastine (10 mg), or placebo the night before (23:00). Binding potential ratios and H1ROs were calculated in different brain regions of interest such as the cingulate gyrus, fronto-temporal cortex, and cerebellum. Subjective sleepiness and plasma drug concentration also were measured. Calculation of binding potential ratios revealed significantly lower values for diphenhydramine than for bepotastine or placebo in all regions of interest (P < 0.01). Cortical mean H1RO after diphenhydramine treatment was 44.7% compared with 16.6% for bepotastine treatment (P < 0.01). Subjective sleepiness was not significantly different among the subjects treated with each test drug or the placebo. In conclusion, the next-day residual sedative effect after nighttime administration of the OTC sleep aid diphenhydramine was verified for the first time by direct PET measurement of H1RO. Taking into account the possible hangover effect of OTC antihistamine sleep aids, care needs to be taken during their administration.

Original languageEnglish
Pages (from-to)694-701
Number of pages8
JournalJournal of Clinical Psychopharmacology
Volume30
Issue number6
DOIs
Publication statusPublished - 2010 Dec

Keywords

  • bepotastine
  • crossover study
  • diphenhydramine
  • histamine H1 receptor occupancy
  • over-the-counter sleep aid
  • positron emission tomography
  • residual sedative effect

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Next-day residual sedative effect after nighttime administration of an over-the-counter antihistamine sleep aid, diphenhydramine, measured by positron emission tomography'. Together they form a unique fingerprint.

Cite this