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Novel Antagonist Shows Potential for MDD in Phase 2 Study

June 15, 2020

A novel vasopressin 1B (V1B) receptor antagonist eased depressive symptoms when used as an adjunctive treatment in patients with major depressive disorder (MDD) in a small phase 2 study published online in the Journal of Psychiatric Research.

“Overall, nonsignificantly greater improvements in depressive symptoms were observed for patients treated with TS-121 compared to those treated with placebo,” researchers wrote, “and the trend was more apparent in patients with higher urinary and hair cortisol levels, which support the concept that V1B receptor antagonists may be most efficacious in individuals who exhibit hypothalamus-pituitary-adrenal (HPA) axis hyperactivity.” 

The double-blind study included 51 patients with MDD, all of whom had an inadequate response to current antidepressant therapy. Patients were randomly assigned to one of three adjunctive treatments: TS-121 10 mg, TS-121 50 mg, or placebo for 6 weeks. Forty-three patients completed the study.

Between baseline and week 6, Montgomery-Åsberg Depression Rating Scale (MADRS) scores dropped an average 9 points for both TS-121 treatment groups compared with 6.4 points for the placebo group, according to the study.

Study Suggests Novel Target for New Antidepressants

“TS-121 groups showed greater numerical reductions in MADRS score change from baseline compared to placebo,” researchers wrote, “though these reductions did not achieve statistical significance.”

Similar trends showing numerically greater, although not statistically significant, improvements with TS-121 compared with placebo were observed across several secondary study endpoints: the Clinical Global Impression-Severity scale, the self-rated Symptoms of Depression Questionnaire, the clinician-rated Hamilton Anxiety Rating Scale, percentage of MADRS responders, and percentage of Clinical Global Impression-Improvement improvers.

“These findings combined with favorable safety and tolerability warrant further investigation of TS-121 in an adequately powered study in patients with major depressive disorder,” researchers advised.

—Jolynn Tumolo


Kamiya M, Sabia HD, Marella J, et al. Efficacy and safety of TS-121, a novel vasopressin V1B receptor antagonist, as adjunctive treatment for patients with major depressive disorder: a randomized, double-blind, placebo-controlled study. Journal of Psychiatric Research. 2020 May 31;[Epub ahead of print].

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