Centre for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Québec, Canada.
Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de PharmacoVigilance, Pharmacoépidémiologie et d'Informations sur le Médicament, Centre Hospitalier Universitaire, Faculté de Médecine, Toulouse, France.
JAMA Psychiatry. 2019 Apr 1;76(4):409-417. doi: 10.1001/jamapsychiatry.2018.4149.
Some reports have raised concerns regarding a potential psychiatric worsening associated with first-time use of aripiprazole in patients already treated with other antipsychotic medications. Whether aripiprazole use, particularly in the long term, increases the risk for serious psychiatric events is unclear.
To assess whether switching to or adding aripiprazole is associated with serious psychiatric treatment failure compared with switching to or adding another antipsychotic drug in patients previously exposed to antipsychotic medications.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study was conducted from January 1, 2005, to March 31, 2015. Data were obtained from the United Kingdom Clinical Practice Research Datalink, one of the world's largest computerized databases linked to the Hospital Episodes Statistics repository and the Office for National Statistics (ONS) mortality database. Within a base cohort of new users of antipsychotic drugs, patients switching or adding aripiprazole (n = 1643) were propensity matched 1:1 to patients switching to or adding another antipsychotic medication (n = 1643). All patients were followed up until psychiatric treatment failure, for 365 days (1 year) after cohort entry, until death from any cause other than suicide, until end of registration or linkage with the databases, or end of the study period (March 31, 2016).
Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of serious events of psychiatric treatment failure (psychiatric hospitalizations, self-harm, or suicide) associated with switching to or adding aripiprazole compared with other antipsychotic drugs. In addition to propensity score matching, all models were adjusted for age, number of psychiatric hospitalizations or self-harm events in the 6 months before cohort entry, number of different antipsychotic drugs before cohort entry, and quintiles of the Index of Multiple Deprivation.
The study cohort included 1643 patients (949 [57.8%] were women with a mean [SD] age of 42.1 [16.8] years) starting aripiprazole use; they were matched 1:1 to 1643 patients (871 [53.0%] were women with a mean [SD] age of 42.4 [17.1] years) starting use of another antipsychotic drug. During 2692 person-years of follow-up, 391 incident serious psychiatric treatment failures occurred, with a crude incidence rate of 14.52 (95% CI, 13.16-16.04) per 100 person-years. First-time use of aripiprazole was not associated with an increased rate of psychiatric treatment failure (HR, 0.87; 95% CI, 0.71-1.06), psychiatric hospitalizations (HR, 0.85; 95% CI, 0.69-1.06), or self-harm or suicide (HR, 0.96; 95% CI, 0.68-1.36) compared with starting use of another antipsychotic drug. Results were consistent across several sensitivity analyses.
Initiating aripiprazole use, compared with another antipsychotic medication, after a previous antipsychotic exposure did not appear to be associated with psychiatric hospitalization, self-harm, or suicide; these findings warrant replication in large observational studies.
一些报告引起了人们的关注，即首次使用阿立哌唑治疗已经接受其他抗精神病药物治疗的患者可能会出现潜在的精神恶化。阿立哌唑的使用，特别是长期使用，是否会增加严重精神事件的风险尚不清楚。
评估与转换或添加另一种抗精神病药物相比，转换或添加阿立哌唑是否与先前暴露于抗精神病药物的患者的严重精神治疗失败相关。
设计、地点和参与者：这项基于人群的队列研究于 2005 年 1 月 1 日至 2015 年 3 月 31 日进行。数据来自英国临床实践研究数据链接，这是世界上最大的与医院发病统计数据库和国家统计局（ONS）死亡率数据库链接的计算机化数据库之一。在新使用抗精神病药物的患者基础队列中，转换或添加阿立哌唑的患者（n=1643）与转换或添加另一种抗精神病药物的患者（n=1643）进行了 1:1 的倾向匹配。所有患者均随访至精神治疗失败，从队列入组后 365 天（1 年），至非自杀性其他原因死亡，至与数据库的注册或链接结束，或研究期结束（2016 年 3 月 31 日）。
使用 Cox 比例风险回归模型估计与转换或添加阿立哌唑相比，与转换或添加另一种抗精神病药物相关的严重精神治疗失败（精神病住院、自我伤害或自杀）的风险比（HR）和 95%置信区间（CI）。除了倾向评分匹配外，所有模型还调整了队列入组前 6 个月内精神病住院或自我伤害事件的数量、队列入组前不同抗精神病药物的数量以及多种剥夺指数的五分位数。
研究队列包括 1643 名（949[57.8%]为女性，平均[SD]年龄为 42.1[16.8]岁）开始使用阿立哌唑的患者；他们与 1643 名（871[53.0%]为女性，平均[SD]年龄为 42.4[17.1]岁）开始使用另一种抗精神病药物的患者进行了 1:1 匹配。在 2692 人年的随访期间，发生了 391 例严重精神治疗失败事件，粗发生率为 14.52（95%CI，13.16-16.04）/100 人年。首次使用阿立哌唑与精神治疗失败（HR，0.87；95%CI，0.71-1.06）、精神病住院（HR，0.85；95%CI，0.69-1.06）或自我伤害或自杀（HR，0.96；95%CI，0.68-1.36）的发生率增加无关。在几个敏感性分析中，结果一致。
与使用另一种抗精神病药物相比，在先前的抗精神病药物暴露后开始使用阿立哌唑似乎与精神病住院、自我伤害或自杀无关；这些发现需要在大型观察性研究中进行复制。
