Antidepressants are a rapidly growing class of drugs used to treat depression. The newer agents have been demonstrated to improve patient outcomes and lower overall health cost. Despite these benefits, the cost of the newer antidepressants may be significant and may be influenced by patterns of use. This study was undertaken to examine three potential cost drivers associated with antidepressants: persistence rate; switch rate; and concurrent use of adjunctive antianxiety/sedative/hypnotic therapy. OBJECTIVES: Examine the rates of persistence, switching, and concurrent use of adjunctive antianxiety/sedative/hypnotic agents associated with the newer antidepressants and determine if there is a difference between agents. Our objective was to determine if these differences in pattern of use add “cost” to treatment. Antidepressants studied included fluoxetine, paroxetine, sertraline, and venlafaxine. METHODS: We performed a retrospective analysis of medical and pharmaceutical claims data for 2,000,000 commercial HMO members for a two-year period beginning July 1996. Inclusion criteria for the study were: 1) diagnosis of depression; and 2) no antidepressant use or medical activity related to depression for three months prior to admission to the study. The data were stratified into two groups for review – non-capitated and capitated plans. Statistical analysis was performed comparing each group. RESULTS: There is a statistically significant difference between some agents in the rates of switching and the use of adjunctive medications. As switching increased, total medical cost increased. Medical cost increased to $120 from $104 per depressed member per month at switching rates of 29.5% and 15.3%, respectively. The variation in the use and cost of adjunctive medications was also statistically significant between some agent. The cost ranged from $23.71 to $2.74 for adjunctive medications per depressed member per month. CONCLUSION: When determining which antidepressant drug to use, it is prudent to consider additional costs associated with switching and adjunctive medication.