Are antipsychotics effective adjunctive Tx for patients with moderate-to-severe depression?

YES. Augmentation with second generation antipsychotics, especially aripiprazole and quetiapine, appears to be effective in patients with moderate-to-severe depression who have had a suboptimal response to a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor (strength of recommendation [SOR]: A, based on a systematic review of randomized controlled trials [RCTs] and an individual RCT). Augmenting antidepressant therapy with cariprazine, ziprasidone, or olanzapine also appears to improve depressive symptoms over the short term. All antipsychotics studied carried an increased likelihood of adverse effects that could lead to discontinuation (SOR: A, based on a systematic review of RCTs).