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Introduction Drug-induced liver injury (DILI) is the 4th most common cause of liver damage in Western countries and can be caused by antidepressants. Methods Against the background of increasing antidepressant prescriptions and increasing use of polypharmacy, we analyzed administered antidepressants and other pharmacological substances, liver toxicity, comorbid somatic secondary diseases together with the occurrence of DILI in a patient population of 6 centers throughout Germany. Results The majority of the enrolled 329 patients received polypharmacological treatment in an inpatient setting. During antidepressant treatment 5.1% of the patients had elevated serum transaminase levels, whereby exactly and not more than 1 criterion proposed to be indicative for DILI, was fulfilled by 3 patients (0.9%). Discussion During patient characterization it becomes clear that a sensitization for relevant risk constellations causing liver injury in MDD patients is relevant to prevent further serious adverse events. [ABSTRACT FROM AUTHOR]