OBJECTIVES First-line treatment of MDD patients with a generic SSRI is often encouraged by managed care organizations. However, some patients may require second line therapy. This study evaluates the economic consequences associated with three options of second-line treatment: escitalopram, an SNRI (venlafaxine or duloxetine), or a generic SSRI. METHODS Adult MDD patients treated with a generic SSRI were identified in the Ingenix Impact database (2003-2007) and included if they switched to escitalopram, an SNRI, or another generic SSRI. Urgent care utilization during the 3-month follow-up was compared across these three study cohorts. Costs incurred during three months pre- vs. post-switching date were compared descriptively and using regression analyses adjusting for patient demographics, comorbidities, prior resource use and length of therapy. RESULTS The study identified 7,774 switchers to escitalopram, 10,505 to SNRIs, and 6,723 to a generic SSRI. Compared to escitalopram switchers, patients who switched to an SNRI or a generic SSRI had an increased adjusted risk of mental health-related urgent care utilization (OR=1.30 and 1.17 respectively, both P<0.05). Patients who switched to escitalopram had a $402 reduction in medical costs (P<0.001) during the 3-month follow-up period compared to baseline costs, while switchers to an SNRI had a $254 reduction. However, switchers to a generic SSRI had a $99 increase in medical costs. Controlling for baseline characteristics, escitalopram switchers had the highest total healthcare cost reduction of the three groups, with $383 (P=0.016) in savings relative to SNRI switchers and $172 (P=0.276) in savings relative to switchers to a generic SSRI. CONCLUSIONS MDD patients requiring second line therapy who switched to escitalopram had significantly lower urgent care utilization than patients switching to an SNRI or another generic SSRI. Using escitalopram as second-line therapy appears to be a cost saving strategy compared to using SNRIs or generic SSRIs.