Hepatic outcomes among adults taking duloxetine: a retrospective cohort study in a US health care claims database

BACKGROUND Hepatic injury has been reported following duloxetine use. This study further examines the hepatic safety of duloxetine in a large US health insurance database. METHODS In this propensity score-matched cohort analysis in a US commercially insured population (01 August 2004 to 31 December 2010), we compared individuals with depression and without liver disease who initiated duloxetine to comparators (venlafaxine or selective serotonin reuptake inhibitors [SSRIs], and individuals with pharmacologically untreated depression). We estimated incidence rates (IR) and 95 % confidence intervals (CI) for medical record-confirmed hepatic-related death, liver failure, and other clinically significant hepatic injury. RESULTS Among 30,844 duloxetine initiators, 21,000 were matched to venlafaxine initiators, 28,479 to SSRI initiators, and 22,714 to untreated patients. There were no cases of hepatic-related death or liver failure. IRs of other clinically significant hepatic injury without documented alternate etiologies were higher but not statistically significant among duloxetine initiators compared to initiators of venlafaxine (0.7/1000 person-years [PY] [95 % CI: 0.2 - 1.5] vs. 0.0/1000 PY [95 % CI: 0.0 - 0.3]) and SSRIs (0.4/1000 PY [95 % CI: 0.1 - 1.0] vs. 0.0/1000 PY [95 % CI: 0.0 - 0.3]). IRs were similar among duloxetine and untreated patients (0.5/1000 PY [95 % CI: 0.1 - 1.3] vs. 0.5/1000 PY [95 % CI: 0.1 - 1.5]). When hepatic outcomes were considered irrespective of alternate etiologies, similar results were observed. CONCLUSIONS Our findings, while not statistically significant, may suggest a higher incidence of hepatic injury other than hepatic-related death or liver failure among duloxetine initiators compared to venlafaxine and possibly SSRIs, but not untreated patients. These differences remain consistent with chance, and an elevated risk cannot be ruled in or out.