OBJECTIVES: The study examines patterns of antidepressant use including drug switching and related resource utilization. METHODS: Using retrospective claims of managed care enrollees from a national database (PharMetrics), this study followed newly diagnosed depression patients (age 18+) with newly prescribed antidepressants. Patients switching from commonly prescribed selective serotonin reuptake inhibitors (SSRIs; fluoxetine, citalopram, sertraline, and paroxetine) to serotonin-norepinephrine reuptake inhibitors (SNRI; venlafaxine), and vice versa were identified and quantified. The healthcare costs for a 1-year period following diagnosis for various switcher groups were then aggregated. Multivariate regression analyses were used to determine the predictors of switching and the factors influencing overall and depression-related costs while controlling for confounding factors. RESULTS: Of the 48,950 patients included in the study population, 89% were treated with SSRIs and 11% with SNRIs. Twelve percent to 15% of patients switched antidepressants. Of the SSRI switchers, 29% switched to an SNRI. Increased likelihood of switching was associated with female gender, Medicaid coverage, prior anxiolytic use, treatment by a psychiatrist or psychologist, and paroxetine as the index medication. Compared with SSRI non-switchers, costs for SSRI switchers were 36% higher for all causes and 58% higher for depression-related causes. In contrast, compared with SNRI non-switchers, costs for SNRI switchers were 27% higher for all causes and 5% higher for depression-related causes. Thus, patients switching from SSRI to SNRI are accruing relatively greater costs than vice versa. In addition, among SSRI patients switching to SNRI, costs increased with the number of switches. Mutlivariate analyses confirmed that switching was associated with higher overall and depression-related costs. CONCLUSIONS: Switching among antidepressants is quite frequent among depression patients. Switchers incur significantly higher overall and depression-related costs, and in general, switching antidepressants is more costly for SSRI patients than for SNRI patients.