The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial is the largest open-label, pragmatic trial that has been undertaken to examine the treatment of major depressive disorder. At a cost of US$35 million over 6 years, STAR*D sought to test the effectiveness both of pharmacotherapy and of cognitive therapy, and to ascertain whether certain treatments are more optimal after one or more failed trials.

Patients (n = 2876) who presented to either a psychiatry or family practice setting seeking treatment for depression were included in the STAR*D analysis. In the 4 levels of STAR*D, patients were randomized to various treatment monotherapies, combinations, or augmentation strategies. The primary outcome was remission, based on the Hamilton Depression Rating Scale. Secondary outcomes were response, as measured by clinician and patient self-report as well as various measures of patients' level of function and (or) quality of life.

Remission rates for treatment levels 1 to 2 and 3 to 4 were 18% to 30% and 7% to 25%, respectively. There was no difference in effectiveness between any treatments at any treatment level. Patients with longer index episodes, more concurrent psychiatric or general medical disorders, and (or) lower measures of baseline function were less likely to achieve remission. There were no major differences between outcomes in patients treated in primary, compared with specialist care, nor were there significant differences between depression rating scores obtained through clinician ratings, compared with self-report.

Results of the STAR*D trial have shed important light on the effectiveness of current treatment strategies for patients with depression.