This original study was designed to evaluate the efficacy and safety of reduced B vitamins as monotherapy in adults with major depressive disorder (MDD) who were also positive for at least 1 methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with depression, and further test the hypothesis that reduced (metabolized) B vitamins will lower homocysteine (HCY) in a majority of clinically responding patients. 330 adult patients with MDD (DSM-5), and positive for MTHFR C677T and/or A1298C polymorphisms were enrolled in a trial conducted between August 1, 2014, and April 3, 2015. 160 patients received placebo, while 170 received a capsule containing a combination of reduced B vitamins. Plasma homocysteine levels were measured at baseline and week 8. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate efficacy for MDD. This further analysis is conducted on the resultant data, with patient names withheld. It is an extensive look at the findings to determine if response is correlated with HCY reduction and if other factors may be associated with response or non-response.