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A population-based study of dosing and persistence with anti-dementia medications

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Cholinesterase inhibitors and memantine are the mainstay of pharmacological intervention for the cognitive symptoms of Alzheimer’s disease (AD). This study assessed the adequacy of dosing and persistence with AD medications and the predictors of these variables in the ‘real world’ (outside the clinical trial setting).

Methods

The Health Service Executive–Primary Care Reimbursement Services prescription claims database in the Republic of Ireland contains prescription information for 1.6 million people. Patients aged >70 years who received at least two prescriptions for donepezil, rivastigmine, galantamine and memantine between January 2006 and December 2010 were included in the study. Rates of dose-maximisation were recorded by examining the initiation dose of each AD drug commenced during the study period and any subsequent dose titrations. Non-persistence was defined by a gap in prescribing of more than 63 consecutive days. Predictors of dose-maximisation and non-persistence were also analysed.

Results

Between January 2006 and December 2010, 20,729 patients aged >70 years received a prescription for an AD medication. Despite most patients on donepezil and memantine receiving a prescription for the maximum drug dose, this dose was maintained for 2 consecutive months in only two-thirds of patients. Patients were significantly more likely to have their doses of donepezil and memantine maximised if prescribed in more recent years (2010 vs. 2007). Rates of non-persistence were 30.1 % at 6 months and 43.8 % at 12 months. Older age [75+ vs. <75 years; hazards ratio (HR) 1.16, 95 % confidence interval (CI) 1.06–1.27] and drug type (rivastigmine vs. donepezil; HR 1.15, 95 % CI 1.03–1.27) increased the risk of non-persistence. Non-persistence was lower for those commencing therapy in more recent years (2010 vs. 2007; HR 0.81, 95 % CI 0.73–0.89, p < 0.001) and for those on multiple anti-dementia medications (HR 0.59, 95 % CI 0.54–0.65, p < 0.001). Persistence was significantly higher when memantine was co-prescribed with donepezil (p < 0.0001).

Conclusion

Future studies should explore the reasons underlying non-persistence and failure to maintain dose-maximisation in patients on AD medications. There may be scope to improve the dosing and persistence with these medications in the community.

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Acknowledgements

We would like to acknowledge the Primary Care Reimbursement Services from which this data was derived. The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Geriatric and Stroke Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Beaumont, Dublin 9, Ireland

    Linda Brewer, Cora McGreevy & David Williams

  2. Department of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, St James’s Hospital, Dublin 8, Ireland

    Kathleen Bennett

  3. Education and Research Centre, Smurfit Building, Beaumont Hospital Campus, Beaumont, Dublin 9, Ireland

    Linda Brewer

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  1. Linda Brewer
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Corresponding author

Correspondence to Linda Brewer.

Appendix 1

Appendix 1

Dosing and titration information recommended in specific product characteristics for medicines donepezil and memantine [13].

Medication

Dosing and titration recommendations

Donepezil

Treatment is initiated at 5 mg/day. This dose should be maintained for at least 1 month in order to allow the earliest clinical responses to treatment to be assessed and to allow steady-state concentrations to be achieved. Following a 1-month clinical assessment of treatment at 5 mg/day, the dose can be increased to 10 mg/day (maximum recommended daily dose).

Memantine

The recommended starting dose is 5 mg per day, which is increased over the first 4 weeks of treatment to reach the recommended maintenance dose of 20 mg daily. Week 1: One 5 mg film-coated tablet per day for 7 days. Week 2: One 10 mg film-coated tablet per day for 7 days. Week 3: One 15 mg film-coated tablet per day for 7 days. Week 4: One 20 mg film-coated tablet per day for 7 days.

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Brewer, L., Bennett, K., McGreevy, C. et al. A population-based study of dosing and persistence with anti-dementia medications. Eur J Clin Pharmacol 69, 1467–1475 (2013). https://doi.org/10.1007/s00228-013-1483-y

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  • DOI: https://doi.org/10.1007/s00228-013-1483-y

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