OBJECTIVES: To compare the economic costs and benefits of eszopiclone co-administered with fluoxetine (ESZ+FLX) to that of placebo co-administered with fluoxetine (PBO+FLX) in patients with insomnia and co-morbid MDD. METHODS: Data from 422 patients enrolled in an 8-week, double-blind, placebo-controlled, trial were used to estimate the cost per quality-adjusted life-year (QALY) gained by treating patients’ insomnia with ESZ along with FLX for MDD. The costs of medical care and time away from work were estimated using published algorithms based on scores of the Hamilton Depression Scale (HAM-D17). Cost of lost productivity while at work was based on responses to the Work Limitations Questionnaire collected during the trial. Utilities were estimated via the HAM-D17 scores or the SF-36 scores collected during the trial using published transformation methods. Drug costs were estimated based on average wholesale price, adjusted for standard discounts and dispensing fees. All costs (in 2007 US$) and QALYs were estimated using the 8-week trial data or the trial data extrapolated to 6 months using last observation carried forward. Treatment discontinuations before and after Week 8 were taken into consideration and sensitivity analysis of key parameters was performed. RESULTS: In the base case 8-week analysis using HAM-D17-derived utilities, the mean gains in QALYs were 0.0392 and 0.0334 for the ESZ+FLX and PBO+FLX groups, respectively. Mean 8-week per-patient costs including absenteeism and presenteeism were $1,279 and $1,198, respectively. Thus, eszopiclone with co-administered fluoxetine resulted in an incremental cost per QALY gained of $13,881. When absenteeism and presenteeism costs were excluded, this ratio increased to $29,748. The 6-month trial data extrapolation, including productivity costs, resulted in ESZ+FLX being a cost-saving, QALY-gaining strategy with a cost/QALY of $13,911. CONCLUSIONS: Co-treatment of insomnia with eszopiclone, and MDD with fluoxetine appeared to be economically advantageous for patients with patients with both disorders. [UNKNOWN NODETYPE 9]