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Discontinuation of Cholinesterase Inhibitor Treatment and Determinants thereof in the Netherlands

A Retrospective Cohort Study

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Abstract

Background The Cholinesterase inhibitors (ChEIs) rivastigmine and galantamine have been approved for the treatment of mild to moderate Alzheimer’s disease in the Netherlands. Differences between ChEIs regarding persistence or the use of effeCtive doses in daily Clinical practice have been observed. However, most studies assessing ChEI discontinuation and associated determinants have been Conducted in North America and there is a lack of knowledge about ChEI discontinuation and its determinants in daily Clinical practice in Europe.

Objectives To assess ChEI discontinuation in daily practice in the Netherlands and to seek its determinants, including suboptimal utilization.

Methods A retrospective cohort study was performed using data from the Dutch PHARMO Record Linkage System. Included patients were aged ≥50 years at first dispensing of a ChEI, had a first dispensing of a ChEI between 1998 and 2008, had a prior medication history of 12 months and had at least one subsequent dispensing of any kind of medication. The proportion of patients who discontinued ChEIs over 3 years was determined. Cox regression was used to assess determinants for early (≤6 months) discontinuation and, separately, for late discontinuation during a subsequent 30-month follow-up among those persisting with treatment for >6 months.

Results At 6 months, 30.8% of 3369 study patients had discontinued ChEIs, compared with 59.0% after 3 years. Thirty-five percent of patients taking rivastigmine reached the WHO-defined daily dose compared with 80% taking galantamine. At 6 months, compared with regular-dose rivastigmine, low-dose rivastigmine or low-dose galantamine was associated with an increased risk of early discontinuation, whereas regular-dose galantamine was associated with a decreased risk, as was concurrent use of cardiac medications, drugs for Parkinson’s disease, propulsives, selective serotonin reuptake inhibitors and benzodiazepines. Associations of ChEI type/dose or comedications with discontinuation among patients persisting for >6 months differed somewhat from associations with discontinuation before 6 months.

Conclusions Fewer patients taking rivastigmine than those taking galantamine reached recommended doses. Furthermore, patients taking rivastigmine had an increased risk of early discontinuation compared with patients taking galantamine. Adverse effects leading to treatment intolerance and suboptimal utilization may have been contributing factors to these observed differences.

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Acknowledgements

This study received financial support from the Canadian Institutes for Health Research (CIHR) [research fellowship for E. Kröger], from the division of Pharmacoepidemiology and Pharmacotherapy at Utrecht University (UIPS) and the Centre d’excellence sur le vieillissement de Québec (CEVQ), Québec, Canada. The division of Pharmacoepidemiology and Pharmacotherapy at Utrecht University, which employs T. Egberts and P. Souverein, has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, the private-public funded Top Institute Pharma (www.tipharma.nl, which includes co-funding from universities, government, and industry), the Dutch Medicines Evaluation Board and the Dutch Ministry of Health. The CIHR, UIPS or CEVQ were not involved in the study design, conduct or analyses, or in the preparation of the manuscript. The authors have no conflicts of interest that are directly relevant to the content of this study. The results of this study were presented at the 25th Anniversary International Conference for Pharmacoepidemiology and Drug Safety, Providence, Rhode Island, USA, August 2009.

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Authors and Affiliations

  1. Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands

    Edeltraut Kröger, Patrick Souverein & Toine Egberts

  2. Center of Excellence on Aging, CHA Research Center, Quebec, Canada

    Edeltraut Kröger

  3. Geriatric Department, University Medical Center Utrecht, Utrecht, the Netherlands

    Rob van Marum & Toine Egberts

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  1. Edeltraut Kröger
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Correspondence to Edeltraut Kröger.

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Kröger, E., van Marum, R., Souverein, P. et al. Discontinuation of Cholinesterase Inhibitor Treatment and Determinants thereof in the Netherlands. Drugs Aging 27, 663–675 (2010). https://doi.org/10.2165/11538230-000000000-00000

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