Supplementary Material for: Risk of psychiatric disorders in patients with psoriasis prescribed acitretin versus disease-modifying antirheumatic drugs: a nationwide matched cohort study

Background: Acitretin has been linked to the development of psychiatric disturbance.
Objectives: To assess the psychiatric hazards in patients with psoriasis prescribed acitretin compared with those prescribed disease-modifying antirheumatic drugs (DMARDs).
Methods: This is a nationwide matched cohort study. From Taiwan’s National Health Insurance Research Database, Adult patients with psoriasis between 1997 and 2013 were screened. Patients prescribed acitretin for at least 30 days per year on average (acitretin cohort) were matched 1:2 with those prescribed DMARDs for at least 30 days per year on average (reference cohort), by means of age, gender, and psoriasis duration. Patients prescribed medication of the corresponding cohort for more than 7 days during the observation period were excluded. Cumulative incidences of psychiatric disorders in both cohorts were plotted with the Kaplan-Meier method. The modified Cox regression models were constructed to estimate hazard ratios (HRs).
Results: In total, 1,152 and 2,304 patients in the acitretin and the reference cohort, respectively, were included. The 4-year cumulative incidence of overall psychiatric disorders (19.62% vs. 12.06%; p<.001), mood disorders (12.81% vs. 7.67%; p<.001), and psychosis (7.21% vs. 4.63%; p<.001) in the acitretin cohort were significantly higher than those in the reference cohort. Acitretin was independently associated with psychiatric disorders (HR 1.51, 95% confidence interval [CI] 1.23-1.85). The risk is more accentuated in the subgroups of comorbid chronic liver disease (HR 2.60, 95% CI 1.56-4.33) or psoriatic arthritis (HR 3.23, 95% CI 1.75-5.97). Other independent risk factors included insomnia, acute coronary syndrome, females, and age.
Conclusions: Compared with disease-modifying antirheumatic drugs, acitretin was associated with higher hazards of psychiatric disorders among psoriasis patients.

背景：阿维A（acitretin）与精神障碍的发生存在关联。
目的：对比接受阿维A治疗与接受改善病情抗风湿药（disease-modifying antirheumatic drugs, DMARDs）治疗的银屑病（psoriasis）患者的精神疾病风险。
方法：本研究为一项全国性匹配队列研究。研究数据源自中国台湾地区全民健康保险研究数据库，筛选了1997年至2013年间的成年银屑病患者。将每年平均接受阿维A治疗至少30天的患者（阿维A队列），按年龄、性别及银屑病病程以1:2的比例匹配每年平均接受改善病情抗风湿药治疗至少30天的患者（参考队列）。观察期内对应队列用药时长超过7天的患者被排除。采用Kaplan-Meier法绘制两队列精神障碍的累积发病率曲线，并构建修正Cox回归模型以估算风险比（hazard ratios, HRs）。
结果：最终共纳入阿维A队列1152例患者，参考队列2304例患者。阿维A队列的4年总体精神障碍累积发病率（19.62% vs. 12.06%; p<.001）、心境障碍累积发病率（12.81% vs. 7.67%; p<.001）及精神病性障碍累积发病率（7.21% vs. 4.63%; p<.001）均显著高于参考队列。阿维A与精神障碍存在独立关联（HR=1.51, 95%置信区间（confidence interval, CI）1.23-1.85）。在合并慢性肝病（HR=2.60, 95% CI 1.56-4.33）或银屑病关节炎（HR=3.23, 95% CI 1.75-5.97）的亚组中，该风险更为显著。其余独立危险因素包括失眠、急性冠脉综合征、女性及年龄因素。
结论：与改善病情抗风湿药相比，银屑病患者接受阿维A治疗的精神疾病风险更高。