Association of Suicidality and Depression With 5 alpha-Reductase Inhibitors

作者：Welk Blayne; McArthur Eric; Ordon Michael; Anderson Kelly K; Hayward Jade; Dixon Stephanie

来源：JAMA Internal Medicine, 2017, 177(5): 683-691.

DOI：10.1001/jamainternmed.2017.0089

IMPORTANCE There have been concerns raised by patients and regulatory agencies regarding serious psychiatric adverse effects associated with 5 alpha-reductase inhibitors.
OBJECTIVE To determine if there is an increased risk of suicide, self-harm, or depression among older men starting a 5 alpha-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 5 alpha-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 5 alpha-reductase inhibitor. EXPOSURES Duration of finasteride or dutasteride usage.
MAIN OUTCOMES AND MEASURES Suicide. Secondary outcomeswere self-harm and depression.
RESULTS Men who used 5 alpha-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 5 alpha-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 5a-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 5 alpha-reductase inhibitor (finasteride or dutasteride) did not significantly modify the observed associations with suicide, self-harm, and depression.
CONCLUSIONS AND RELEVANCE In a large cohort of men ages 66 years or older, we did not demonstrate an increased risk of suicide associated with 5 alpha-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 umstancesmay be appropriate.

• 出版日期2017-5