Sequenced Treatment Alternatives to Relieve Depression (STAR*D) (11) data illustrate the complex treatment-resistant and chronic nature of clinical depression. Attainment of wellness (remission) could not be achieved in approximately 30%, even after four levels of treatment with different drug classes, such as those used in step therapy. With each unsuccessful effort, treatment resistance, recurrences, and chronicity became more likely and costs rose. Second, antidepressant treatment and other treatment approaches, such as cognitive-behavioral therapy, to maintain wellness for those with prior repeated episodes of major depressive disorder greatly improve longitudinal functioning (9, 10). For those with prior episodes, recurrences of major depressive disorder are virtually predictable for most individuals if antidepressant treatments are discontinued. Finally, high adherence (compliance) is crucial for both attainment and maintenance of wellness (12). Stated simply, for those that are fortunate enough to be receiving an antidepressant that is effective, staying with the treatment is required for the benefits to persist. Similar lessons were learned for diabetes medications decades ago.