Clinical Drug Investigation

, Volume 23, Issue 6, pp 395–404

Randomised, Double-Blind Study of the Effects of Oxybutynin, Tolterodine, Trospium Chloride and Placebo on Sleep in Healthy Young Volunteers

  • Konstanze Diefenbach
  • Frank Donath
  • Agathe Maurer
  • Sabine Quispe Bravo
  • Klaus-Dieter Wernecke
  • Ulrich Schwantes
  • Jutta Haselmann
  • Ivar Roots
Original Research Article

Abstract

Objective: Central nervous effects of oral anticholinergics may limit the success of incontinence therapy and patient compliance. Only a few studies investigating this topic are available. This study was conducted to determine whether oral anticholinergics alter sleep and psychometric test parameters.

Design: Randomised, double-blind, crossover, placebo-controlled study.

Study participants: 24 healthy volunteers (age 22–36 years) without sleeprelated problems.

Interventions: Polysomnographic recordings, sleep questionnaires and psychometric tests (the number combination test [Zahlen-Verbindungs Test; ZVT] and the d2 attention test) were performed following single doses of oxybutynin 15mg, tolterodine 4mg, trospium chloride 45mg or placebo, each separated by an 8-day washout period.

Results: Rapid eye movement (REM) sleep (relative to total sleep time) was the primary parameter of polysomnography. The REM sleep for oxybutynin was significantly lower than that for trospium chloride (18.4% vs 20.2%; p < 0.05) and lower than that for placebo (20.1%; ns). The number combination test (ZVT), the primary parameter of cognitive function, and the d2 test did not reveal any differences in reaction time. With regard to the other sleep parameters, the REM latency for oxybutynin was clearly higher than that for placebo, trospium chloride and tolterodine. Effects on non-REM sleep were observed only after administration of oxybutynin compared with placebo.

Conclusions: Oxybutynin influenced sleep structure, as was reflected by REM suppression and mild sedation, while subjective parameters and psychometric tests remained unaffected. The sleep and psychometric test values for tolterodine and trospium chloride were comparable to those of placebo. The clinical relevance of these effects is small in healthy young volunteers, but these results cannot be extended to the elderly.

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Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Konstanze Diefenbach
    • 1
  • Frank Donath
    • 1
  • Agathe Maurer
    • 1
  • Sabine Quispe Bravo
    • 1
  • Klaus-Dieter Wernecke
    • 2
  • Ulrich Schwantes
    • 3
  • Jutta Haselmann
    • 3
  • Ivar Roots
    • 1
  1. 1.Institute of Clinical Pharmacology, Charité University Medical CentreHumboldt University of BerlinBerlinGermany
  2. 2.Institute of Medical Biometry, Charité University Medical CentreHumboldt University of BerlinBerlinGermany
  3. 3.Department of Medical Science/Clinical ResearchDr R. Pfleger GmbHBambergGermany

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