Carryover effect on next-day sleepiness and psychomotor performance of nighttime administered antihistaminic drugs: A randomized controlled trial

Yasuko Katayose, Sayaka Aritake, Shingo Kitamura, Minori Enomoto, Akiko Hida, Kiyohisa Takahashi, Kazuo Mishima

Research output: Contribution to journalArticle

18 Citations (Scopus)


Background Antihistamines with strong sedative-hypnotic properties are frequently prescribed for insomnia secondary to allergy, but the potential risks of such administration have not been fully elucidated. Subjects and methods This randomized, double-blind, placebo-controlled crossover study was conducted to evaluate next-day sleepiness and psychomotor performance following the administration of antihistamines. Twenty-two healthy male participants participated in four drug administration sessions with more than a 1-week interval between the sessions. Either zolpidem 10 mg, or diphenhydramine 50 mg, or ketotifen 1 mg, or a placebo was administered before sleep, and polysomnography was conducted to evaluate sleep. In the morning and afternoon of the day after administration, the participants were evaluated for subjective sleepiness, objective sleepiness, and psychomotor performance. Results The antihistamines with high blood-brain barrier-crossing efficiency were significantly associated with sleepiness and psychomotor performance decline the next day. Ketotifen showed the strongest carryover effect, followed by diphenhydramine. Compared with the placebo, no significant carryover effect was observed with zolpidem. Conclusion The results suggest that the risk-benefit balance should be considered in the ready use of antihistamines that easily cross the blood-brain barrier for alleviating secondary insomnia associated with allergies.

Original languageEnglish
Pages (from-to)428-436
Number of pages9
JournalHuman Psychopharmacology
Issue number4
Publication statusPublished - 2012 Jul
Externally publishedYes



  • antihistaminic drugs
  • carryover effect
  • diphenhydramine
  • ketotifen
  • zolpidem

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Pharmacology (medical)

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