OBJECTIVES: To compare changes in total and mental health-related costs after initiation of treatment with aripiprazole (ARP) or extended-release quetiapine (QTP XR) among patients with bipolar disorder (BD) in managed care plans. METHODS: A retrospective cohort study using US claims data assigned adult patients with BD to ARP or QTP XR cohorts based on first prescription filled between June 1, 2007 and June 30, 2008. The index date was the date of treatment initiation. Patients were continuously insured from 6 months before through 6 months after the index date. Per-patient changes in total and mental health-related costs over this period were compared using Wilcoxon rank-sum tests. RESULTS: A total of 287 patients with BD were initiated on QTP XR and 4554 were initiated on ARP. Reductions in total and mental health-related costs were greater among patients initiated on QTP XR than patients on ARP. Mean per patient reduction in costs for total health-related services was $1368 for QTP XR and $8 for ARP (P=0.0290). Mean mental health-related costs were reduced by $1303 with QTP XR compared with an increase of $302 per patient (P<0.001) with ARP. Average per-patient reduction in all-cause hospitalization costs was $2577 for QTP XR and $1394 for ARP (P=0.0064), and the reduction in mental health-related hospitalization costs was $2195 for QTP XR and $1038 for ARP (P=0.0028). The increase in average total pharmacy costs was $1229 for QTP XR and $1543 for ARP per patient (P=0.0219). The increase in average mental health-related pharmacy costs was $1163 for QTP XR and $1451 for ARP (P<0.01). There were no differences in mean total and mental health-related outpatient costs between treatments.CONCLUSIONS: Patients with BD initiated on QTP XR had significantly greater reductions in mean total and mental health-related costs compared with patients initiated on ARP.