Umetsu Ryogo, Abe Junko, Ueda Natsumi, Kato Yamato, Matsui Toshinobu, Nakayama Yoko, Kinosada Yasutomi, Nakamura Mitsuhiro
Laboratory of Drug Informatics, Gifu Pharmaceutical University.
Biol Pharm Bull. 2015;38(11):1689-99. doi: 10.1248/bpb.b15-00243.
Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of depression worldwide. SSRIs are suspected to increase the risk of suicidal ideation and behavior (suicidality) in children, adolescents, and young adults. We examined the association between SSRI therapy and suicidality by applying a logistic regression model to age-stratified data from the Food and Drug Administration (FDA) Adverse Event Reporting System database. We attempted to mitigate the effect of patient-related factors by data subsetting. We selected case reports for SSRIs as referred to in the World Health Organization Anatomical Therapeutic Chemical classification code N06AB. The association between SSRIs and "suicidal events" or "self-harm events" was calculated as a reporting odds ratio (ROR) and adjusted for covariates by logistic regression. For subjects <18 years old (y.o.) the adjusted RORs (95% confidence interval) of SSRI therapy with suicidal events were 9.58 (8.97-10.23) in the whole data analysis and 4.64 (4.15-5.19) in the subset analysis; those with self-harm events were 31.40 (27.71-35.58) and 16.31 (13.12-20.29), respectively. Although the adjusted RORs were lower in the subset analyses than in the whole data analyses, both analyses indicated associations between SSRI treatment and suicidal and self-harm events. In both analyses these associations were stronger in the <18 y.o. group than other age groups. Children and adolescents should be closely monitored for the occurrence of suicidality when they are prescribed SSRIs. In addition, we found that data subsetting might mitigate the effect of an intrinsic risk among patients taking the suspected drug.
选择性5-羟色胺再摄取抑制剂(SSRI)在全球范围内被用于治疗抑郁症。人们怀疑SSRI会增加儿童、青少年和青年的自杀意念及行为(自杀倾向)风险。我们通过对美国食品药品监督管理局(FDA)不良事件报告系统数据库中按年龄分层的数据应用逻辑回归模型,研究了SSRI治疗与自杀倾向之间的关联。我们试图通过数据子集化来减轻患者相关因素的影响。我们选择了世界卫生组织解剖治疗化学分类代码N06AB中提及的SSRI病例报告。计算SSRI与“自杀事件”或“自残事件”之间的关联作为报告比值比(ROR),并通过逻辑回归对协变量进行调整。对于年龄小于18岁的受试者,在整个数据分析中,SSRI治疗与自杀事件的调整后ROR(95%置信区间)为9.58(8.97 - 10.23),在子集分析中为4.64(4.15 - 5.19);与自残事件相关的调整后ROR分别为31.40(27.71 - 35.58)和16.31(13.12 - 20.29)。尽管子集分析中的调整后ROR低于整个数据分析中的值,但两种分析均表明SSRI治疗与自杀及自残事件之间存在关联。在两种分析中,这些关联在年龄小于18岁的组中比其他年龄组更强。当给儿童和青少年开SSRI处方时,应密切监测他们是否出现自杀倾向。此外,我们发现数据子集化可能会减轻服用可疑药物患者的内在风险影响。