Approximately half of patients with MDD treated with SSRIs have a complete remission, which leaves the rest with either partial remission or no remission at all. Typically, when patients do not fully respond to first line medication, clinicians will change to another SSRI or switch to an antidepressant from a different class. The different class is usually an SNRI such as venlafaxine, or a norepinephrine-dopamine reuptake inhibitor, bupropion. The STAR-D trial previously looked at remission rates in patients who did not respond to citalopram who were then randomized to discontinuation of the citalopram and replacing that with sustained-release bupropion, sertraline, or extended-release venlafaxine. The remission rate on second-line medication was approximately 25% with no statistically differences between the 3 groups.¹ The use of an atypical antipsychotic agent was not examined in that trial, though its use has since been demonstrated to have efficacy in the treatment of depression.² The current study adds to our knowledge by comparing switching to bupropion, augmentation with bupropion, or augmentation with an antipsychotic, aripiprazole. While only the strategy of augmentation with aripiprazole was significantly better then switching to bupropion, all strategies had efficacy for greater than 20% of patients, and a strategy of augmentation with bupropion was not statistically inferior to augmentation with aripiprazole. —Neil Skolnik, MD

1. Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006; 354:1231-1242.
2. Arbaizar B, Dierssen-Sotos T, Gómez-Acebo I, Llorca J. Aripiprazole in major depression and mania: meta-analyses of randomized placebo-controlled trials. Gen Hosp Psychiatry. 2009;31(5):478-483. doi:10.1016/j.genhosppsych.2009.05.005.