Treatment with rivastigmine or galantamine and risk of urinary incontinence: results from a Dutch database study

Pharmacoepidemiol Drug Saf. 2015 Mar;24(3):276-85. doi: 10.1002/pds.3741. Epub 2015 Feb 4.

Abstract

Background: Treatment of Alzheimer disease (AD) with cholinesterase inhibitors (ChEIs) may increase the risk of urinary incontinence (UI).

Objective: To assess whether ChEI use was associated with the risk of UI among older patients with AD.

Methods: A crossover cohort study using the PHARMO Record Linkage System included 10 years of data on drug dispensing histories for over two million Dutch residents. Included patients were aged 50 +, free of UI for the last 6 months, received a first ChEI prescription during the study period, had at least 12 months prior drug exposure history and one subsequent prescription of any drug. UI was defined as a first dispensing of a urinary spasmolytic or of incontinence products for at least 30 days. Cox regression with time-varying covariates and multivariate adjustment allowed assessing whether UI incidence was associated with ChEI exposure.

Results: Among 3154 patients there were 657 UI cases during a mean follow-up of 5.1 years before a first ChEI dispensing, and 499 cases after ChEI initiation, during a mean follow-up of 2.0 years. Among the 2700 participants free of UI one year before ChEI initiation, the adjusted hazard ratio (HR) for UI was 1.13 (95% CI: 0.97-1.32) when periods with ChEI use were compared to periods without ChEI use. Sensitivity analyses may suggest an increased risk in the 1(st) month after ChEI initiation (HR: 1.72, p = 0.09) CONCLUSION: Worsening AD may increase incidence of UI, but no firm association between ChEI treatment and risk of UI could be shown from these data.

Keywords: Alzheimer disease; cholinesterase inhibitors; database cohort study; pharmacoepidemiology; urinary incontinence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / epidemiology
  • Cholinesterase Inhibitors / adverse effects*
  • Cohort Studies
  • Cross-Over Studies
  • Databases, Factual* / trends
  • Female
  • Follow-Up Studies
  • Galantamine / adverse effects*
  • Humans
  • Longitudinal Studies
  • Male
  • Netherlands / epidemiology
  • Risk Factors
  • Rivastigmine / adverse effects*
  • Treatment Outcome
  • Urinary Incontinence / chemically induced*
  • Urinary Incontinence / epidemiology*

Substances

  • Cholinesterase Inhibitors
  • Galantamine
  • Rivastigmine