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Tolerability of Cholinesterase Inhibitors: A Population-Based Study of Persistence, Adherence, and Switching

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Abstract

Background

Cholinesterase inhibitors (ChEIs) are prescribed to dementia patients despite their poor tolerance. Low tolerability potentially reduces persistence and adherence, while inducing switching between medications. Comparisons of these utilization measures contribute to knowledge of the relative tolerability of these medications.

Aim

The aim was to compare persistence, adherence, and switching between donepezil, galantamine, oral rivastigmine, and rivastigmine patch.

Methods

A population-based cohort study, using British Columbia claims data (2009–2013), assessed ChEI new users aged 40 and older. We conducted survival analysis to compare persistence and Poisson regression to estimate switching rates. Good adherence, defined as a medication possession ratio of ≥80%, was modeled using log-binomial regression. Analyses were adjusted using propensity scores.

Results

Patients on galantamine had longer mean persistence and better adherence compared with patients on donepezil, with a hazard ratio for discontinuation of 0.91 [95% confidence interval (CI) 0.87–0.96] and a relative risk for good adherence of 1.01 (95% CI 1.002–1.03). Rivastigmine was associated with the shortest mean persistence [3.6 months (95% CI 3.0–4.2) and 5.0 (95% CI 4.7–5.3) for oral and patch, respectively] and the highest mean switching rates. Comparing the two rivastigmine preparations, the patch was associated with decreased discontinuation compared with oral [hazard ratio 0.79 (95% CI 0.71–0.89)] and decreased switching [relative risk 0.63 (95% CI 0.46–0.87) during the first 6 months of treatment]. Paradoxically, the patch was also associated with poorer adherence [relative risk for good adherence 0.94 (95% CI 0.91–0.98)] than the oral formulation.

Conclusions

Based on estimates of persistence, adherence, and switching, galantamine was the best tolerated ChEI and rivastigmine the least.

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Authors and Affiliations

  1. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada

    Anat Fisher, Greg Carney, Ken Bassett & Colin R. Dormuth

  2. Department of Family Medicine, University of British Columbia, 5950 University Boulevard, Vancouver, BC, V6T 1Z3, Canada

    Ken Bassett

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Correspondence to Anat Fisher.

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Funding

The study is funded by the Pharmaceutical Services Division, Ministry of Health, Provincial Government of British Columbia as part of the Alzheimer’s Drug Therapy Initiative (ADTI) for the purpose of developing evidence for the use of ChEI treatment in the community. All inferences, opinions, and conclusions drawn in this publication are those of Anat Fisher, Greg Carney, Ken Bassett, and Colin R. Dormuth, and do not reflect the opinions or policies of the BC Ministry of Health.

Conflicts of interest

Anat Fisher, Greg Carney, Ken Bassett, and Colin R. Dormuth declare that they have no conflicts of interest directly relevant to the content of this study.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Clinical Research Ethics Board, the University of British Columbia, and the Human Research Ethics Board, the University of Victoria. For this type of study formal consent is not required.

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Fisher, A., Carney, G., Bassett, K. et al. Tolerability of Cholinesterase Inhibitors: A Population-Based Study of Persistence, Adherence, and Switching. Drugs Aging 34, 221–231 (2017). https://doi.org/10.1007/s40266-017-0438-x

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