We conducted a 6-week double-blind, placebo-controlled, augmentation study comparing the efficacy and safety of MSI-195 800 mg (a proprietary formulation of S-adenosylmethionine) or placebo added to ongoing antidepressant medication (ADT) in acutely depressed subjects with Major Depressive Disorder (MDD) who had experienced an inadequate response to their ongoing ADT (The Horizon Study, ClinicalTrials.gov NCT01912196). There were 234 eligible subjects randomized to either MSI-195 (n = 118) or placebo (n = 116). There were no overall statistically significant differences found between MSI-195 added to ongoing ADT compared to placebo on any of 3 depression-rating instruments (HamD17, MADRS, IDS-SR30) in the ITT set. MSI-195 was generally safe and well tolerated with predominantly mild gastrointestinal side effects. Post-hoc analyses examined factors that might have affected study outcome. The ITT set was divided into subjects enrolled during the 1st half (first nine months) and 2nd half of the study. MSI-195 added to ongoing ADT was significantly better than placebo on both the HamD17 and MADRS in the 1st half (p = 0.03 and 0.02 respectively), but not in the 2nd half of the study. Several demographic and clinical characteristics were significantly different between the two study segments including body mass index, pre-randomization symptom severity fluctuation, number of lifetime depressive episodes, and anxious depression sub-type. Thus, the characteristics of the enrolled subjects changed between the 1st and 2nd half of the study. These post-hoc findings highlight the inherent challenges encountered for subject selection in double-blind, placebo controlled trials and compel further investigation of enrollment criteria and moderating factors that affect treatment. The favorable safety profile and clinical benefit observed with MSI-195 in the 1st half of this study warrant further investigation in MDD.
Keywords: Augmentation treatment; Body mass index; Major depressive disorder; Moderating factors; S-adenosylmethionine.
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