This study aims to evaluate the effectiveness and safety of milsaperidone as an add-on treatment for Major Depressive Disorder (MDD). The primary goal is to measure the improvement in depressive symptoms after six weeks of treatment, using the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary objectives include assessing milsaperidone's impact on overall clinical severity and improvement, as measured by CGI-S and CGI-C scales, and tracking adverse events to determine the drug's safety and tolerability. The study also seeks to understand the drug’s effect on serum urate levels, including potential interactions with genetics and demographics. Finally, exploratory research includes genomic scanning to identify potential safety markers and assess the influence of individual genetic variations on treatment response.

The study is designed as a multi-center, randomized, double-blind, placebo-controlled trial with a parallel-group structure. It comprises three phases: a pre-randomization phase (screening and baseline visits), a short-term treatment phase (double-blind titration and treatment periods), and an optional open-label extension (OLE) phase. Participants initially taking a stable dose of their existing antidepressant medication will be randomized to receive either milsaperidone or a placebo in addition to their current treatment.