The demand for knowledge about differences in effectiveness, tolerability, safety, and economic outcomes between and within groups of antidepressant drugs when used in routine daily clinical practice is growing. For gaining this knowledge, observational pharmacoepidemiologic studies are often the most feasible option. However, the results of such studies can only be valid if either patient baseline characteristics associated with the outcome under study are similar or if differences can be adjusted for in the analysis. The aim of this study was to evaluate to what extent and for what type of patients three antidepressant drugs recently introduced in The Netherlands (mirtazapine, sertraline, and venlafaxine) were prescribed during the first year after their introduction and whether there were differences compared with longer-available antidepressant drugs. For this purpose, prescription drugs histories from 20 pharmacies serving a population of approximately 200,000 persons were analyzed. One year after their introduction, the newly introduced antidepressant t drugs accounted for approximately 6% of new uses of all antidepressant drugs. In comparison to longer-available antidepressant, the newly introduced antidepressant drugs were more often prescribed for patients with prior prescriptions of another antidepressant drug (rate ratio [RR] 2.7 [95% confidence interval [CI], 2.3-3.0]), for patients with prior prescriptions of other psychotropic medicines (RR 1.3 [95% CI, 1.1-1.4), and by psychiatrists (RR 1.9 [95% CI, 1.6-2.2]). In addition, the newly introduced antidepressant drugs seemed to be more often, although not significantly, prescribed for patients who had been hospitalized on a psychiatric ward (RR 1.5 [95% CI, 0.9-2.5]). No differences were observed with regard to age and gender distribution, the total number of medicines prescribed, and prescriptions of any cardiovascular or gastrointestinal medicine. These finding suggest that a significant proportion of the patients receiving one of the newly introduced antidepressant drugs did not respond satisfactorily to previous pharmacologic treatment. This channeling phenomenon may have important consequences for the interpretation of observational comparisons between different antidepressant drugs after their introduction.