(290) Risk of Intentional Self Harm and Suicide Among 5-Alpha Reductase Inhibitor Users and Alpha-Blocker Users

Publication Number: 621

Background: Reliable observational studies assessing the risk of intentional self-harm (ISH) or suicide among 5-alpha reductase inhibitor (5-ARI) users continue to be scarce. A large cohort study of older men with benign prostatic hyperplasia (BPH) reported an increased risk of ISH with 5-ARI use compared to non-users; however, the potential for confounding by indication complicates interpretation of these findings and highlights the need for more rigorous research using a more suitable comparator group.

Objectives: To compare risk of ISH, suicide, and a composite outcome of ISH or suicide in older men treated with 5-ARIs vs. alpha-blockers for BPH.

Methods: Using Medicare data linked to the National Death Index (NDI) from Jan 1, 2007 through Dec 31, 2016, we implemented a new user, active comparator, retrospective cohort design in males aged 65 and older with BPH who initiated treatment with 5-ARIs (dutasteride 0.5mg or finasteride 5mg) or alpha-blockers (alfuzosin, silodosin, and tamsulosin) that are indicated for BPH. ISH events were identified by ICD-9-CM and ICD-10-CM diagnosis codes in inpatient or outpatient emergency department settings. Suicides were identified through cause-of-death information from NDI. We used inverse probability of treatment weighted (IPTW) Cox proportional hazards regression to compare time-to-event between the two treatment groups, with robust variance estimation. Statistical significance was determined using 95% confidence intervals (CIs) of hazard ratios (HRs) and two-tailed-tests (p-value ≤ 0.05).

Results: In a weighted population of new users of 5-ARIs (n=181,675) and alpha-blockers (n=850,476), the event rates for ISH diagnosis and suicide were 0.314 and 0.308 per 1000 person-years (PY) among 5-ARI users, and 0.364 and 0.382 per 1000PY among alpha-blocker users. Compared to alpha-blocker users, the HRs for ISH and suicide were 0.88 (95% CI: 0.62–1.25) and 0.82 (95% CI: 0.54–1.24), respectively. For the composite outcome of ISH or suicide, the HR was 0.88 (95% CI: 0.66–1.16). Subgroup analyses by Charlson and frailty score categories, reason for initial Medicare eligibility, anxiety, depression, age-group, and race did not substantially change the magnitude or direction of the estimates.

Conclusions: 5-ARI use was not associated with an increased risk of ISH or suicide as compared to alpha-blocker use in older men with BPH. Study limitations included low event rates and potentially low sensitivity for ISH events. This publication reflects the views of the authors and should not be construed to represent FDA’s views or policies.