OBJECTIVES: Approximately one-half of patients with an episode of major depression will have a recurrent episode during their lifetime. Recent studies indicate that approximately 20% of depressed patients are resistant to traditional antidepressant treatments. This study utilizes medical and prescription claims data from the 1995-1998 MarketScan® Databases to profile the characteristics and healthcare utilization of patients with treatment-resistant depression. METHODS: Depression-diagnosed patients with adequate antidepressant dosing and treatment duration are selected. Patients are classified as treatment-resistant if they have switched/augmented their initial medication with other antidepressants twice, or if they have switched/augmented their initial medication and have claims for depression-related hospitalizations or suicide attempts. Depression-diagnosed patients meeting selection criteria but not classified as treatment-resistant by the above criteria are used as a comparison group. RESULTS: Patients with treatment-resistant depression are at least twice as likely to be diagnosed with bipolar disorder, at least 1.5 times as likely to be diagnosed with comorbid anxiety disorders, and at least 1.5 times as likely to be diagnosed with substance-related disorders than the comparison group (p-values<0.01). Patients with treatment-resistant depression have 30% higher mean number of psychiatric diagnostic groupings (PDG) and 9% higher mean number of major diagnostic categories (MDC) than the comparison group (p-values<0.01). Furthermore, patients with treatment-resistant depression are at least twice as likely to be hospitalized (depression and non-depression related), and have 41% more outpatient visits than the comparison group (p-values<0.01). Finally, patients with treatment-resistant depression use 2 to 3 times more psychotropic medications (in addition to antidepressants) than the comparison group (p-values<0.01). CONCLUSIONS: Treatment-resistant patients are higher utilizers of both depression-related and general medical services. This finding underscores the importance of early identification and effective treatment of treatment-resistant patients to prevent future depressive episodes and to mitigate health care utilization.