What are the comparative benefits and harms of augmentation treatments in major depression?

The majority of depressed patients do not experience sufficient response to their initial antidepressant medication. Augmentation strategies, particularly the use of atypical antipsychotics to augment selective serotonin reuptake inhibitors (SSRIs), have proliferated over the last 15 years, and 2 atypical antipsychotics, aripiprazole and quetiapine, have received US Food and Drug Administration approval for adjunctive therapy in treatment-resistant depression. Alternatively, data in treatment-resistant depression exist for most of the atypicals and for other treatments, including lithium, bupropion, methylphenidate, pindolol, and buspirone.