Major depression is the most common serious brain disorder with a lifetime prevalence of up to 17%. Despite numerous options currently available for the treatment of depression, ~2 million people in the United States may experience an inadequate response to treatment (treatment-resistant depression [TRD]) at some point in their lives. The definition of TRD is variable, ranging from a failure to respond to two or more trials of antidepressant monotherapy to a failure to respond to four or more trials of different antidepressant therapies, including augmentation, combination therapy, and electroconvulsive therapy. It has been reported that as many as one-third of patients experience only a partial response to initial therapy, while nearly one-fifth are considered nonresponders. In addition to the obvious quality of life issues for the patient with TRD, the economic cost of TRD is significant. Annual healthcare costs increase significantly for patients with TRD with each successive change in antidepressant medication. Early in treatment (two medication changes), the annual costs are <$7,000/Year. By the eighth medication change, annual costs double to nearly $14,000/year.
There is a well-documented need for better long-term treatments for TRD, as witnessed by multiple efforts to establish treatment algorithms and best treatment steps when first and subsequent treatment measures prove inadequate. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, which analyzed outcome following several standardized antidepressive treatment steps, reported that 33% of patients did not respond even after four evidence-based treatment steps. A substantial proportion of patients are inadequately treated and some of these will go on to suffer from chronic, debilitating, and life-threatening symptoms.