Background: Sedation can be a beneficial effect of medication, but it can also be an unwanted side-effect, especially in patients who have to work. The aim of this study is to analyze whether physicians prescribe sedative antidepressants differently for patients at work vs. those on sick leave. Methods: A drug utilization study of mirtazapine was conducted for 12 weeks on 594 depressed outpatients from 227 general practitioners or psychiatrists. There were 319 patients working and 275 patients on sick leave. The two groups were compared regarding sociodemographic variables, illness characteristics, mode and course of treatment. Results: As expected, patients on sick leave were sicker than working patients; they were treated by specialists more often and received higher dosages of mirtazapine. Work status had no influence on dosage after controlling for severity of illness, patient sex, and physician specialty. The overall improvement of depression was similar in both patient groups. Under treatment with mirtazapine, 64.5% of patients on sick leave returned to work, while 2.6% of the patients initially at work went on sick leave by the end of the 12 weeks. Sedation as an undesired side-effect was reported in less than 1%. The rate of sedative polypharmacy declined during treatment with mirtazapine. Conclusion: The results suggest that in routine treatment physicians do not see a need to adjust prescribing of mirtazapine because of its sedative properties to the working status of the patients. The majority of patients on sick leave returned to work. Mirtazapine can help to reduce sedative polypharmacy.