OBJECTIVE: Antidepressants are frequently used for the treatment of depressive and anxiety disorders. Three major classes of antidepressants are selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and other antidepressants. The objectives of this study are to describe drug price and utilization trends in each subcategory of antidepresants. METHODS: The First DataBank national drug file was used to calculate the monthly average wholesale price (AWP) per daily dose from 1986 to 2002. Using the Centers for Medicare & Medicaid Services prescription drug database, we constructed quarterly per-prescription reimbursement figures for each drug from 1991 to 2004. Descriptive interrupted time-series analyses were conducted to quantify drug utilization and price trends. RESULTS: The average AWP per daily dose for all branded drugs increased over time regardless of new agent entry or patent expiration. The reimbursement costs per prescription for Prozac and Luvox dropped when their generics entered. The average cost per SSRI prescription increased from $60 in 1991 to $110 in 2001, then decreased to $90 in 2004 due to generic entry. The proportion of total expenditure for SSRIs increased from 13% in 1991 to 57% in 2004, while spending on TCAs decreased from 74% in 1991 to 12% in 2004. CONCLUSIONS: Large increases in antidepressant drug expenditures have accompanied increased SSRI utilization. With growing concerns over high drug expenditure, we need to explore more the factors affecting drug-pricing strategy.