Aim: To assess anxiolytic and sleep improving effects of mirtazapine (15-60 mg/day) in depressed outpatients in an open-label, non-comparative, naturalistic study.Materials and Methods: Patients in need of pharmacological treatment with antidepressants as assessed by psychiatrists or GPs in The Netherlands, were included in the study. Participating psychiatrists were working in different clinical settings, involving primary, outpatient and inpatient care. A specially developed check-list in Dutch language for global assessments of efficacy and safety by a physician were used in this study. The patients were assessed at screening, and 1, 2 to 3 weeks and 3 months after beginning the treatment with mirtazapine. The investigators had the option either to start with mirtazapine 15 mg/day for 4 days, and to increase to 30 mg/day from day 5, or to start with 30 mg/day from day 1 onwards. The maximum allowed dosage of mirtazapine was 60 mg/day. Two subgroups were identified among patients diagnosed with depression (n = 539): with high baseline anxiety (n = 329) and sleep disturbances (n = 473). Efficacy and tolerability of mirtazapine were assessed during a 3-month treatment period.Results: Improvements in depressed mood, symptoms of anxiety and sleep disturbances, as assessed by check-list, were seen in similar percentages of anxious patients at each visit and at endpoint. In general, a global improvement at endpoint in either symptom was seen in approximately 65% of patients. The overall drop out rate in anxious patients was 21%, while the percentage of patients complaining of at least one adverse event progressively decreased during the study period, from 46% at visit 1 to 21% at visit 3. The only adverse events registered in more than 5% of patients were somnolence at all three visits (in 29%, 18% and 8% of patients, respectively), and dizziness in 9% and 5% of patients at first 2 visits. The patient population with high initial sleep disturbance responded favourable to treatment with mirtazapine. Improvements in mood, symptoms of anxiety and sleep disturbances were seen at endpoint in 66%, 45% and 70% of patients, respectively. The overall dropout rate was 20%. As in the subgroup of anxious patients, the percentage of patients complaining of at least one adverse event progressively decreased during the study period, from 46% at visit 1 to 21% at week 3. The only adverse events reported in more than 5% of patients were somnolence (in 28%, 19% and 9% of patients at 3 assessment times) and dizziness in 9% of patients at week 1. In conclusion, the results of this open-label study suggest that mirtazapine has favorable efficacy and is well tolerated in depressed outpatients presenting with high anxiety or sleep disturbances.