Department of Geriatric and Stroke Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Beaumont, Dublin 9, Ireland.
Eur J Clin Pharmacol. 2013 Jul;69(7):1467-75. doi: 10.1007/s00228-013-1483-y. Epub 2013 Feb 27.
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).
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.
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).
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.
胆碱酯酶抑制剂和盐酸美金刚是治疗阿尔茨海默病（AD）认知症状的主要药物。本研究评估了在“真实世界”（临床试验环境之外）中，AD 药物的剂量和持续使用情况及其预测因素。
爱尔兰卫生服务管理局-初级保健报销服务处方数据库包含了 160 万人的处方信息。2006 年 1 月至 2010 年 12 月期间，年龄>70 岁且至少两次接受过多奈哌齐、卡巴拉汀、加兰他敏和盐酸美金刚处方的患者被纳入本研究。通过检查研究期间开始使用的每种 AD 药物的起始剂量以及随后的剂量调整，记录剂量最大化率。停药超过 63 天定义为停药。还分析了剂量最大化和停药的预测因素。
2006 年 1 月至 2010 年 12 月期间，年龄>70 岁的 20729 名患者接受了 AD 药物处方。尽管大多数接受多奈哌齐和盐酸美金刚治疗的患者服用了最大药物剂量，但只有三分之二的患者连续两个月维持该剂量。如果患者在最近几年（2010 年与 2007 年相比）接受处方，其多奈哌齐和盐酸美金刚的剂量更有可能最大化。6 个月时的停药率为 30.1%，12 个月时为 43.8%。年龄较大（75 岁以上与<75 岁；风险比[HR]1.16，95%置信区间[CI]1.06-1.27）和药物类型（卡巴拉汀与多奈哌齐；HR 1.15，95%CI 1.03-1.27）增加了停药的风险。最近几年（2010 年与 2007 年相比；HR 0.81，95%CI 0.73-0.89，p<0.001）开始治疗和同时使用多种抗痴呆药物（HR 0.59，95%CI 0.54-0.65，p<0.001）的患者停药风险较低。当盐酸美金刚与多奈哌齐同时使用时，患者的持续用药率显著提高（p<0.0001）。
未来的研究应探讨 AD 药物治疗患者停药和无法维持剂量最大化的原因。在社区中，可能有机会改善这些药物的剂量和使用情况。
