Neurosciences Department, University of Padua, Padua, Italy.
Padua Neurosciences Center, University of Padua, Padua, Italy.
Schizophr Bull. 2022 Jan 21;48(1):166-175. doi: 10.1093/schbul/sbab087.
People with schizophrenia/schizoaffective disorder (schizophrenia) die early, largely due to cardiovascular-related mortality. Antipsychotics are associated with lower mortality. We aimed to explore whether antipsychotic use can reduce discontinuation of medications for cardiovascular risk factors and diseases ("cardiometacolic drugs"), using a within-study design controlling for subject-related factors.
Persons diagnosed with schizophrenia between 1972 and 2014, aged <65 years at cohort entry were identified in Finnish national databases. Four subcohorts were formed based on cardiometabolic drug use during the follow-up period, 1996-2017, namely statin (n = 14,047), antidiabetic (n = 13,070), antihypertensive (n = 17,227), and beta-blocker (n = 21,464) users. To control for subject-related factors, including likelihood of adherence as a trait characteristic, we conducted a within-subject study comparing the risk of discontinuation of each cardiometabolic drug during periods on vs off antipsychotics within each subject. We also accounted for number of psychiatric and nonpsychiatric visits in sensitivity analyses.
In 52,607 subjects with schizophrenia, any antipsychotic use vs nonuse was associated with decreased discontinuation risk of antidiabetics (adjusted hazard ratio [aHR] = 0.56, 95% confidence interval [CI] = 0.47-0.66), statins (aHR = 0.61, 95%CI = 0.53-0.70), antihypertensives (aHR = 0.63, 95%CI = 0.56-0.71), and beta-blockers (aHR = 0.79, 95%CI = 0.73-0.87). Antipsychotics ranking best for discontinuation of all cardiometabolic drug categories were clozapine (aHR range = 0.34-0.55), followed by olanzapine (aHR = 0.43-0.71). For statins, aHRs ranged from aHR = 0.30 (95%CI = 0.09-0.98) (flupentixol-long-acting injectable (LAI) to aHR = 0.71 (95%CI = 0.52-0.97) (risperidone-LAI), for anti-diabetic medications from aHR = 0.37 (95%CI = 0.28-0.50) (clozapine) to aHR = 0.70 (95%CI = 0.53-0.92) (quetiapine), for antihypertensives from aHR = 0.14 (95%CI = 0.04-0.46) (paliperidone-LAI) to aHR = 0.69 (95%CI = 0.54-0.88) (perphenazine), for beta-blockers from aHR = 0.55 (95%CI = 0.48-0.63) (clozapine) to aHR = 0.76 (95%CI = 0.59-0.99) (perphenazine-LAI). The decreased risk of discontinuation associated with antipsychotic use somewhat varied between age strata. Sensitivity analyses confirmed main findings.
In this national database within-subject design study, current antipsychotic use was associated with substantially decreased risk of discontinuation of statins, anti-diabetics, antihypertensives, and beta-blockers, which might explain reduced cardiovascular mortality observed with antipsychotics in people with schizophrenia.
精神分裂症/分裂情感障碍(精神分裂症)患者的死亡率较高,主要是由于心血管相关死亡率较高。抗精神病药物与较低的死亡率相关。我们旨在通过控制与患者相关的因素,使用研究内设计来探索抗精神病药物的使用是否可以减少心血管风险因素和疾病(“心脏代谢药物”)的药物停药率。
在芬兰国家数据库中确定了 1972 年至 2014 年间被诊断为精神分裂症且入组时年龄<65 岁的患者。根据随访期间心脏代谢药物的使用情况,将患者分为四个亚组,即他汀类药物(n=14047)、抗糖尿病药物(n=13070)、抗高血压药物(n=17227)和β-受体阻滞剂(n=21464)使用者。为了控制与患者相关的因素,包括作为特质特征的依从性可能性,我们进行了一项研究内比较,即在每个患者中,比较抗精神病药物治疗期间与非治疗期间每种心脏代谢药物停药的风险。我们还在敏感性分析中考虑了精神科和非精神科就诊的次数。
在 52607 例精神分裂症患者中,与非使用抗精神病药物相比,任何抗精神病药物的使用均与抗糖尿病药物(调整后的危险比[aHR] = 0.56,95%置信区间[CI] = 0.47-0.66)、他汀类药物(aHR = 0.61,95%CI = 0.53-0.70)、抗高血压药物(aHR = 0.63,95%CI = 0.56-0.71)和β-受体阻滞剂(aHR = 0.79,95%CI = 0.73-0.87)的停药风险降低相关。抗精神病药物排名最佳的所有心脏代谢药物类别是氯氮平(aHR 范围=0.34-0.55),其次是奥氮平(aHR = 0.43-0.71)。对于他汀类药物,aHR 范围从 aHR = 0.30(95%CI = 0.09-0.98)(氟哌啶醇长效注射剂(LAI)至 aHR = 0.71(95%CI = 0.52-0.97)(利培酮-LAI),对于抗糖尿病药物,aHR = 0.37(95%CI = 0.28-0.50)(氯氮平)至 aHR = 0.70(95%CI = 0.53-0.92)(喹硫平),对于抗高血压药物,aHR = 0.14(95%CI = 0.04-0.46)(帕利哌酮-LAI)至 aHR = 0.69(95%CI = 0.54-0.88)(奋乃静),对于β-受体阻滞剂,aHR = 0.55(95%CI = 0.48-0.63)(氯氮平)至 aHR = 0.76(95%CI = 0.59-0.99)(奋乃静-LAI)。抗精神病药物使用与停药风险降低之间的关联在年龄层次上有所不同。敏感性分析证实了主要发现。
在这项全国性数据库内研究设计研究中,当前抗精神病药物的使用与他汀类药物、抗糖尿病药物、抗高血压药物和β-受体阻滞剂停药风险显著降低相关,这可能解释了精神分裂症患者使用抗精神病药物后心血管死亡率降低的原因。