OBJECTIVES: To compare costs and healthcare utilizations in pharmacotherapy, psychotherapy, and combined therapy groups for treatment of depression. METHODS: Depressed individuals 18-65 years were identified from 1998-2006 Medical Expenditure Panel Survey. Individuals with other mental health illnesses were excluded. Three mutually exclusive groups were formed: (1) Pharmacotherapy group had at least four antidepressant prescriptions yearly and no psychotherapy, (2) Psychotherapy group had at least four psychotherapy visits yearly and no antidepressants, (3) Combined therapy group included patients with at least four psychotherapy visits and four antidepressants yearly. Yearly mean costs and utilizations were estimated for the three groups using generalized linear regression models adjusted for demographics, geographic diversity, income status, insurance type, perceived mental and physical health status, and co-morbidities. RESULTS: Combined therapy group had the highest total healthcare cost ($10610) followed by pharmacotherapy ($7464) and psychotherapy groups ($5371), (p-value for differences among the three groups [p] <0.0001). Mental health-related costs for combined therapy, pharmacotherapy and psychotherapy groups were $1233, $766 and $516 respectively (p<0.0001). Ambulatory costs were highest for the combined therapy group ($4686) followed by the psychotherapy group ($3126) and pharmacotherapy group ($2241), (p<0.0001). Inpatient cost for the combined therapy, pharmacotherapy and psychotherapy groups were $2185, $2112, and $638, respectively (p=0.001). Prescription cost was $3451 for combined therapy group, $2895 for pharmacotherapy group and $1423 for psychotherapy group (p<0.0001). Number of ambulatory visits for combined therapy, pharmacotherapy, and psychotherapy groups was 32.24, 11.36, and 22.36, respectively (p<0.0001). Combined therapy group had the maximum number of prescriptions (42.23), followed by the pharmacotherapy group (38.94) and psychotherapy group (17.19), (p<0.0001). CONCLUSIONS: Combined therapy group was the highest and psychotherapy group was the lowest in terms of costs and utilization for each component analyzed. Health decision makers may consider both effectiveness and costs for each treatment type.