OBJECTIVES: HEDIS guidelines recommend patients with depression remain on antidepressant therapy for a minimum of six months to receive full clinical benefit. This study compared differences in healthcare costs based upon length of SSRI therapy. METHODS: Continuously eligible patients >18 years of age receiving SSRI therapy diagnosed as having depression in a managed Medicaid program from July 1, 1999 to December 31, 2000 were eligible for study inclusion. Length of therapy was defined as total SSRI days supply acquired within six months of the index date. Patients were placed into the following cohorts based upon length of therapy or drug utilization patterns: 1) <90 days; 2) 90-179 days; 3) >180 days; or 4) Switched/Augmented (SA). Differences in pharmaceutical, professional, hospital and total healthcare costs were evaluated across the four cohorts over a 1-year follow-up period. RESULTS: There were 2250 patients meeting all inclusion criteria. Only 34% of patients received >180 days of therapy. While 24% had <90 days of therapy, 21% had 90-179 days and 21% had evidence of switching/augmentation. Demographic and background covariates were similar across all cohorts. As expected, pharmaceutical charges increased as length of therapy increased, being highest in the SA cohort. However, as length of therapy increased from <90 days to >180 days, professional services and hospital charges decreased by an average of $816 annually per patient. Total monthly healthcare costs in the >180 day cohort remained stable after at least 6 months of SSRI treatment through the full 12-months that patients were followed. CONCLUSIONS: Pharmaceutical costs increased as SSRI length of therapy improves. However, healthcare costs decreased due to reductions in hospital and professional service charges for patients maintained on SSRIs for at least the recommended six months of continuous therapy.