BACKGROUND: Depression often occurs simultaneously with a variety of somatic, psychiatric, and social conditions. Knowledge about differences in the pharmacological treatment of depressed patients with and without co-morbidity is lacking. OBJECTIVE: To compare GPs' pharmacological treatment of depressed patients with and without co-morbidity. METHODS: Data were extracted from the computerized medical records of 77 general practices participating in the Dutch National Information Network of General Practice (LINH). We used diagnosis and prescription data of newly diagnosed depressed patients aged 18-65 years (n=4372). A mixed-model technique was used for analyzing the medical data. RESULTS: During the year after diagnosing depression, depressed patients who also suffered from chronic somatic or psychiatric morbidity were prescribed more psychotropics than patients with depression only. Prescription patterns of psychotropic drugs for depressed patients with and without co-morbid social problems differed only during the first 3 months after diagnosis. For the whole 1-year period after diagnosis, the pharmacological treatment of depression in patients with and without co-morbid social problems did not differ. CONCLUSION: Our results indicate that chronic somatic or psychiatric co-morbidity in depressed patients leads to higher GP prescription levels of psychotropics, whereas co-morbid social problems do not seem to influence GPs' pharmacological treatment decisions for depression. (aut. ref.