Which Adjunctive Antipsychotic Is Best for Major Depression?

<jats:p>In a network meta-analysis of five FDA-approved adjuncts for MDD, lumateperone led on response rates, with aripiprazole close behind. However, the analysis excluded lithium, olanzapine, and quetiapine IR despite their supporting evidence. Aripiprazole showed the lowest discontinuation rates and lumateperone the highest. However, fixed 42 mg dosing may explain lumateperone's poorer tolerability, and it was the only one without concerning weight gain. Generic aripiprazole ($16/month) and quetiapine IR ($9/month) cost far less than brexpiprazole or lumateperone (~$1,500–$1,800/month). The newer agents were not clearly superior, so cost should weigh heavily in selection.</jats:p>