OBJECTIVES: To estimate the cost-effectiveness of atypical antipsychotics (AAPs) in the treatment of acute mania in patients with bipolar I disorder from a managed care perspective. METHODS: The model estimated the cost-effectiveness (CE) ratios for each AAP when used as monotherapy for the acute (3-week) treatment of patients with bipolar mania. CE ratios were defined as the total annual cost per responder, and responders were defined as patients with a °Ý50% improvement on the YMRS scale at 3 weeks. Data sources included published literature, package inserts, and primary data analysis of a managed care claims database. The median response rate for each AAP was used in the base case scenario; 45.5%, 50.0%, 58.0%, 53.3%, and 56.7% for aripiprazole, ziprasidone, risperidone, quetiapine, and olanzapine, respectively. Since there are no published head to head comparisons between all AAPs, response rates were obtained from individual studies for each AAP. Total annual costs were calculated based on 1.3 acute manic episodes per year and included costs of AAPs, concurrent medications, adverse events, and medical resource utilization. All costs were inflated to 2005 values. Incremental cost-effectiveness and sensitivity analyses will be conducted. RESULTS: The total annual costs per patient were $7897, $7778, $7807, $7730, and $7829 for aripiprazole, ziprasidone, risperidone, quetiapine, and olanzapine, respectively. Given the response rates and costs per patient listed above, the CE ratios were $17,356, $15,555, $13,360, $14,504, and $13,807, respectively. CONCLUSIONS: These findings suggest that, among AAPs, treatment with risperidone may be the most cost-effective choice for acute management of mania in patients with bipolar I disorder. The results of this model are limited to a 3-week acute treatment of mania, thus no conclusions can be drawn about the cost-effectiveness of AAPs when used as maintenance treatment.