OBJECTIVES: To evaluate the impact of identifying and intervening upon inefficient dosing practices related to atypical antipsychotics in a large commercial managed care organization. METHODS: An analysis using the Interactive Prescribing Efficiency Tool (iPET) was conducted to identify inefficient prescribing among atypical antipsychotics. Pill combinations used to reach all daily doses for the atypicals were identified and baseline opportunity cost savings calculated. A pharmacy claims edit was instituted for all atypicals on July 1, 2004. Prescriptions were flagged at the pharmacy level if inefficient dosing was present and automatic optimization of regimens was implemented based on predetermined algorithms. The iPET was used to reevaluate the success of this intervention at improving economic outcomes. RESULTS: We identified 1,215 patients receiving an atypical antipsychotic during the pre-intervention period (aripiprazole n=153; olanzapine n=284; quetiapine n=469; risperidone n=289; ziprasidone n=81). Some patients may have received multiple atypicals. Inefficient pill combinations may have been received by 7.8%, 18.7%, 27.9%, 27.7%, and 23.5% of aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone patients, respectively. An opportunity savings of $157,401 in overall atypical antipsychotic expenditures was estimated (if up to 70% of inefficient doses were converted to more efficient pill combinations). In the period after the dose optimization program had been implemented, we identified 1,166 patients as receiving an atypical (aripiprazole n=158; olanzapine n=258; quetiapine n=463, risperidone n=250; ziprasidone n=80). During this period, inefficient pill combinations may have been received by 4.4%, 8.5%, 38.9%, 10.0%, and 20% of aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone patients, respectively. The opportunity savings dropped to $58,385 indicating a costs savings of $99,016 following the implementation of the dose optimization intervention. CONCLUSION: Substantial improvements in economic outcomes were realized through an intervention focused on increasing prescribing efficiency among the atypical antipsychotics.