Objective: To assess month-by-month changes in clinical characteristics of patients initiating on duloxetine, a new antidepressant, during the first two years following its initial availability in the U.S. Methods: Retrospective claims analysis of Pharmetrics managed care health plan patients initiating on duloxetine between September 1, 2004 and August 31, 2006. A total of 102,567 duloxetine initiators were identified for inclusion in this study. Monthly data series for demographic and clinical characteristics were created on the basis of Cymbalta initiation date. Claims within +/-30 days of initiation were used to identify clinical characteristics. Results: Demographic patterns of patients initiating on duloxetine remained stable over the two year period (average monthly percent female 73.0%; average monthly age 47.4 years), as did proportions of patients with any anxiety (20.7%) or a GAD diagnosis (5.6%). The average monthly % of patients treated by mental health specialists trended downward over the first 16 months of the study period (from 32.3% to 23.7%), while the % with a depression diagnosis trended downward (51.0% to 45.4%) for the first 12 months, before stabilizing thereafter. The % of patients with a pain diagnosis increased over the first three months (62.4% to 66.6%) and remained stable thereafter. Of those with a depression diagnosis, the % with an MDD diagnosis trended downward (55.8% to 45.8%) for 15 months before stabilizing, while the % of those with MDD diagnosed with Recurrent MDD remained stable over the entire study period (77.8%). Conclusion: Demographic characteristics of patients initiating on duloxetine in the two years following initial availability in the U.S. have remained relatively stable. Clinical characteristics have shown some variation, particularly over the first 12 to 16 months following initial availability. These trends in utilization have implications for the selection of appropriate methodologies for developing cohorts for comparing utilization and costs between new and established antidepressant medications.