For most patients with major depressive disorder (MDD) the first-line treatment is one of the selective serotonin reuptake inhibitors (SSRIs). However, some practitioners prefer to utilize a serotonin norepinephrine reuptake inhibitor (SNRI) or the norepinephrine-dopamine reuptake inhibitor bupropion as their first-line antidepressant treatments (Slide 1). Differences of opinion regarding first, second, or third choice of antidepressant often stem from regional practices or individual training.

A basic standard of practice in MDD treatment is to initiate monotherapy trials with several first-line choices of antidepressants before moving on to alternate strategies. This basic strategy was evaluated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Only approximately one third of the patients remitted after being treated with the study's first-line treatment, a 12-week trial of citalopram in doses up to 60 mg/day. As in other contemporary treatment studies, remission was defined as virtually complete relief of depressive symptoms. This is defined as a Hamilton Rating Scale for Depression score of ≤7 or a score of ≤5 on the self-report version of the Quick Inventory of Depressive Symptomatology.

For those who did not obtain an adequate response to the initial course of citalopram therapy, the STAR*D study compared several alternate treatments, including switching to another antidepressant, adjunctive therapy with another type of medication (ie, a medication that is not an antidepressant), or combination treatment (ie, adding another antidepressant). At the end of four sequential treatment trials, only approximately two thirds of the patients remitted. Of those, 40% to 70% relapsed within the next year despite continued therapy.