Major depressive disorder (MDD) is widespread, costly, and frequently chronic. Internationally, the burden of depression is large and growing. By the year 2020, this disorder is projected to be the world's second leading cause of disease burden. The costs associated with depression are enormous; people with depression tend to have approximately double the health care costs of unaffected individuals. There are few other major disorders that have a negative health impact of the same magnitude.

Early onset of depressive symptoms, along with underdiagnosis and undertreatment, contribute to the burden of MDD, which is also characterized by chronicity, frequent relapses, and recurrences. Risk factors for depressive recurrence include the presence of residual symptoms, >3 prior depressive episodes, chronic depression lasting more than 2 years, a family history of mood disorders, other comorbidities (eg, terminal illness, diabetes), and late onset (>60 years of age). Patients who have any of these factors should be candidates for maintenance treatment.

Naturalistic studies have demonstrated that most patients with MDD without sustained treatment will eventually experience a relapse or recurrence. Furthermore, depressive episodes tend to become more autonomous over time, with decreased linkage to stressful life events, more severe, and potentially more refractory with each new relapse or recurrence. Researchers and clinicians have observed that rather than only treat or manage relapses or recurrences of MDD, the best strategy may be prevention of depressive episodes. As a result, current strategies seek to treat patients to remission, which translates to a lower overall risk of developing relapses or recurrences compared with those patients who continue to demonstrate residual symptoms. Thus, a consistent body of evidence now supports continuous pharmacotherapy for the prevention of depressive relapse and recurrence.