Duloxetine for depression and the incidence of hepatic events in adults.

Elevated hepatic enzyme levels and hepatic injuries have been associated with duloxetine use in clinical trials and spontaneous reports, but the association of duloxetine with a broad spectrum of hepatic outcomes has not been assessed observationally. This cohort study of adult duloxetine initiators between 2004 and 2006 based on the Ingenix Research Data Mart involved 6 matched comparator cohorts, including 4 antidepressant initiator groups (venlafaxine, nefazodone, selective serotonin reuptake inhibitors, and tricyclic antidepressants), depressed but untreated patients, and individuals without depression. The cohorts were followed up for hepatic events, and proportional hazards regression compared duloxetine initiators with comparator cohorts, whereas Poisson regression compared duloxetine usage categories to account for changed therapy during follow-up. Approximately 64,000 person-years among 21,457 duloxetine initiators and comparator cohorts yielded 51 hepatic outcome events. Venlafaxine initiators (incidence rate ratio [IRR] = 0.34; 95% confidence interval [CI], 0.12-0.95) and the cohort without depression (IRR = 0.30; 95% CI, 0.10-0.93) had lower incidences of combined hepatic events than duloxetine initiators, whereas no other differences in hepatic events were observed for duloxetine initiators relative to selective serotonin reuptake inhibitors, tricyclic antidepressants, and untreated depressed patients. In as-treated analyses, relative to nonuse, current (IRR = 4.30; 95% CI, 1.45-12.81) and recent (IRR = 5.93; 95% CI, 1.63-21.55) duloxetine use was associated with greater incidence of less severe hepatic outcomes but not hepatic-related death and potential acute hepatic failure. Although duloxetine does not seem to increase the risk of hepatic-related death or acute hepatic failure, it may be associated with an increased risk of certain less severe hepatic events.