Hepatotoxicity related to anti-depressive psychopharmacotherapy: Implications of quantitative signal detection

Introduction Drug-induced liver injury is a major problem of pharmacotherapy and is also frequent with anti-depressive psychopharmacotherapy. Objectives/aims However, there are only few studies using a consistent methodologic approach to study hepatotoxicity of a larger group of antidepressants. Methods We performed a quantitative signal detection analysis using pharmacovigilance data from the Uppsala monitoring center from the WHO that records adverse drug reaction data from worldwide sources; we calculated reporting odds ratios (ROR) as measures for disproportionality within a case-/non-case approach for several frequently prescribed anti-depressants. Results Both positive controls, amineptine (ROR 38.4 [95% CI: 33.8–43.6]) and nefazodone (ROR 3.2 [95% CI: 3.0–3.5]), were statistically associated with hepatotoxicity. Following amineptine, agomelatine (ROR 6.4 [95% CI: 5.7–7.2]) was associated with the second highest ROR, followed by tianeptine (ROR 4.4 [95% CI: 3.6–5.3]), mianserin (ROR 3.6 [95% CI: 3.3–3.4]) and nefazodone. Conclusions In line with previous studies our results support the hypothesis that agomelatine and several other anti-depressants may be associated with relevant hepatotoxicity. However, the used data and applied method do not allow a quantitative evaluation of hepatotoxicity or assessment of substance–specific differences regarding the extent of hepatotoxicity.