Duloxetine is a dual acting antidepressant (selective serotonin and norepinephrine reuptake inhibitor). Existing data suggest that the advisable therapeutic serum level of duloxetine ranges between 20 and 80 ng/mL. In a naturalistic setting we determined duloxetine serum levels within a steady state in a sample of depressive inpatients by high performance liquid chromatography (HPLC). The mean serum levels in 28 patients at the time of the first TDM analysis were 52.0+/-67 ng/mL. Eight of the patients were smokers and showed a considerably lower serum level of 24.3+/-18.8 ng/mL. In the further course of treatment the difference was compensated by application of higher doses in smokers. These findings suggest that smoking is associated with lower duloxetine serum levels due to an induction of CYP1A2 by polycylic hydrocarbons which are contained in tobacco smoke. Therefore in smokers higher doses of duloxetine (about 15%) seem to be necessary to reach adequate serum levels.