Welk Blayne, McArthur Eric, Ordon Michael, Anderson Kelly K, Hayward Jade, Dixon Stephanie
Department of Surgery, Western University, London, Ontario, Canada2Institute for Clinical Evaluative Sciences, London, Ontario, Canada3Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
Institute for Clinical Evaluative Sciences, London, Ontario, Canada.
JAMA Intern Med. 2017 May 1;177(5):683-691. doi: 10.1001/jamainternmed.2017.0089.
There have been concerns raised by patients and regulatory agencies regarding serious psychiatric adverse effects associated with 5α-reductase inhibitors.
To determine if there is an increased risk of suicide, self-harm, or depression among older men starting a 5α-reductase inhibitor for prostatic enlargement.
DESIGN, SETTING, AND PARTICIPANTS: A population-based, retrospective, matched cohort study using linked administrative data for 93 197 men ages 66 years or older (median [IQR] age, 75 [70-80] years) in Ontario, Canada, who initiated a new prescription for a 5α-reductase inhibitor during the study period (2003 through 2013). Participants were matched (using a propensity score that included 44 of our 96 covariates that included medical comorbidities, medication usage, and health care system utilization) to an equal number of men not prescribed a 5α-reductase inhibitor.
Duration of finasteride or dutasteride usage.
Suicide. Secondary outcomes were self-harm and depression.
Men who used 5α-reductase inhibitors were not at a significantly increased risk of suicide (HR, 0.88; 95% CI, 0.53-1.45). Risk of self-harm was significantly increased during the initial 18 months after 5α-reductase inhibitor initiation (HR, 1.88; 95% CI, 1.34-2.64), but not thereafter. Incident depression risk was elevated during the initial 18 months after 5α-reductase inhibitor initiation (HR, 1.94; 95% CI, 1.73-2.16), and continued to be elevated, but to a lesser degree, for the remainder of the follow-up period (HR, 1.22; 95% CI, 1.08-1.37). The absolute increases in the event rates for these 2 outcomes were 17 per 100 000 patient-years and 237 per 100 000 patient-years, respectively. The type of 5α-reductase inhibitor (finasteride or dutasteride) did not significantly modify the observed associations with suicide, self-harm, and depression.
In a large cohort of men ages 66 years or older, we did not demonstrate an increased risk of suicide associated with 5α-reductase inhibitor use. However, the risk of self-harm and depression were increased compared with unexposed men. This is in keeping with postmarketing experience and patient concerns, and discontinuation of the medication in these circ umstances may be appropriate.
患者和监管机构已对与5α-还原酶抑制剂相关的严重精神不良反应表示担忧。
确定开始使用5α-还原酶抑制剂治疗前列腺增生的老年男性中自杀、自残或抑郁风险是否增加。
设计、设置和参与者：一项基于人群的回顾性匹配队列研究，使用加拿大安大略省93197名66岁及以上男性（年龄中位数[四分位间距]，75[70 - 80]岁）的关联行政数据，这些男性在研究期间（2003年至2013年）开始新处方5α-还原酶抑制剂。参与者通过倾向评分（包括我们96个协变量中的44个，涵盖医疗合并症、药物使用和医疗保健系统利用情况）与相同数量未开具5α-还原酶抑制剂处方的男性进行匹配。
非那雄胺或度他雄胺的使用时长。
自杀。次要结局是自残和抑郁。
使用5α-还原酶抑制剂的男性自杀风险未显著增加（风险比，0.88；95%置信区间，0.53 - 1.45）。在开始使用5α-还原酶抑制剂后的最初18个月内自残风险显著增加（风险比，1.88；95%置信区间，1.34 - 2.64），但此后未增加。在开始使用5α-还原酶抑制剂后的最初18个月内新发抑郁风险升高（风险比，1.94；95%置信区间，1.73 - 2.16），并且在随访期的剩余时间内持续升高，但程度较轻（风险比，1.22；95%置信区间，1.08 - 1.37）。这两种结局的事件发生率绝对增加分别为每100000患者年17例和每100000患者年237例。5α-还原酶抑制剂的类型（非那雄胺或度他雄胺）并未显著改变观察到的与自杀、自残和抑郁的关联。
在一大群66岁及以上的男性中，我们未证明使用5α-还原酶抑制剂会增加自杀风险。然而，与未暴露的男性相比，自残和抑郁风险增加。这与上市后经验和患者担忧一致，在这些情况下停药可能是合适的。
