Suh Dong-Churl, Arcona Stephen, Thomas Simu K, Powers Christopher, Rabinowicz Adrian L, Shin Hyunchul, Mirski Dario
Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey 08854, USA.
Drugs Aging. 2004;21(6):395-403. doi: 10.2165/00002512-200421060-00004.
Cholinesterase inhibitors may offer some improvement in the behavioural symptoms of Alzheimer's disease. The dual inhibitory mechanism of action of rivastigmine (inhibition of acetylcholinesterase and butyrylcholinesterase) may improve behavioural symptoms and may delay the need for antipsychotics. This study was conducted to investigate the effect of rivastigmine on the time to first antipsychotic drug use among patients with Alzheimer's disease, compared with patients with Alzheimer's disease not treated with a cholinesterase inhibitor.
This study used MarketScan research databases from 1 January 1999 to 31 March 2002. Patients were included if they: (a). were diagnosed with Alzheimer's disease on two occasions or filled a prescription for rivastigmine for the first time during the index period from 1 July 2000 to 31 December 2001; (b). were 65 years of age and older; (c). had continuous health and prescription insurance coverage during the entire study period; and (d). had not used an antipsychotic medication within 18 months prior to their index Alzheimer's disease prescription or diagnosis. The 'no cholinesterase inhibitor' group included patients who were newly diagnosed with Alzheimer's disease, but did not use any cholinesterase inhibitors. Chi-square, Student's t-, and log-rank tests were used to test differences in study variables between groups. Cox proportional hazards models were used to estimate predicted risk of first antipsychotic drug use.
The study included 497 patients in the rivastigmine group and 749 patients in the 'no cholinesterase inhibitor' group. The rivastigmine group patients were younger compared with the 'no cholinesterase inhibitor' group patients (p < 0.01). The overall usage of antipsychotics was considerably lower for patients taking rivastigmine (9.8%) compared with those not taking cholinesterase inhibitors (25.6%). Patients taking rivastigmine were 64% less likely (relative risk = 0.36; p < 0.0001) to take antipsychotics compared with patients not taking cholinesterase inhibitors, after adjusting for demographic covariates, comorbid conditions, and use of other CNS drugs and anticonvulsants. Age was the only other factor that influenced antipsychotic use; older patients were significantly more likely to start antipsychotics than younger patients.
This study provides initial evidence that patients with Alzheimer's disease treated with rivastigmine have a reduced risk of initiating therapy with an antipsychotic drug compared with patients who receive no cholinesterase inhibitor treatment. These findings may imply that rivastigmine use could delay the onset of behavioural symptoms that require treatment with antipsychotic medications.
胆碱酯酶抑制剂可能会在一定程度上改善阿尔茨海默病的行为症状。卡巴拉汀的双重抑制作用机制（抑制乙酰胆碱酯酶和丁酰胆碱酯酶）可能会改善行为症状，并可能延迟使用抗精神病药物的必要性。本研究旨在调查与未接受胆碱酯酶抑制剂治疗的阿尔茨海默病患者相比，卡巴拉汀对阿尔茨海默病患者首次使用抗精神病药物时间的影响。
本研究使用了1999年1月1日至2002年3月31日的MarketScan研究数据库。纳入的患者需满足以下条件：（a）在两次诊断中被确诊为阿尔茨海默病，或在2000年7月1日至2001年12月31日的索引期内首次开具卡巴拉汀处方；（b）年龄在65岁及以上；（c）在整个研究期间拥有持续的健康和处方药保险；（d）在索引期阿尔茨海默病处方或诊断前18个月内未使用过抗精神病药物。“无胆碱酯酶抑制剂”组包括新诊断为阿尔茨海默病但未使用任何胆碱酯酶抑制剂的患者。采用卡方检验、学生t检验和对数秩检验来检验组间研究变量的差异。使用Cox比例风险模型来估计首次使用抗精神病药物的预测风险。
研究纳入了497名卡巴拉汀组患者和749名“无胆碱酯酶抑制剂”组患者。卡巴拉汀组患者比“无胆碱酯酶抑制剂”组患者更年轻（p < 0.01）。服用卡巴拉汀的患者抗精神病药物的总体使用率（9.8%）显著低于未服用胆碱酯酶抑制剂的患者（25.6%）。在调整了人口统计学协变量、合并症以及其他中枢神经系统药物和抗惊厥药物的使用情况后，服用卡巴拉汀的患者使用抗精神病药物的可能性比未服用胆碱酯酶抑制剂的患者低64%（相对风险 = 0.36；p < 0.0001）。年龄是影响抗精神病药物使用的唯一其他因素；老年患者开始使用抗精神病药物的可能性明显高于年轻患者。
本研究提供了初步证据，表明与未接受胆碱酯酶抑制剂治疗的患者相比，接受卡巴拉汀治疗的阿尔茨海默病患者开始使用抗精神病药物治疗的风险降低。这些发现可能意味着使用卡巴拉汀可以延迟需要抗精神病药物治疗的行为症状的出现。
