NSI-189 phosphate, a novel neurogenic compound, selectively benefits moderately depressed patients: A post-hoc analysis of a phase 2 study of major depressive disorder

Karl K. Johe, Gary Kay, Santosh Kumar, Katherine E. Burdick, Roger S. McLntyre, George I. Papakostas, Maurizio Fava

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

background: NSI-189 phosphate (NSI-189) is a novel neurogenic molecule with pleiotropic properties, including antidepressant, procognitive, synaptoplastic, and neurotrophic activities demonstrated in preclinical studies. Its antidepressant activity is monoamine-independent. NSI-189 was previously tested in patients with recurrent major depressive disorder in an inpatient setting. methods: This study involved 220 patients randomized to an NSI-189 40-mg dose, NSI-189 80-mg dose, or placebo daily for 12 weeks. The study utilized the sequential parallel comparison design, in which the drug effect was tested in 2 separate stages of 6 weeks each. Herein, post-hoc analyses of the data are presented. results: NSI-189's antidepressant effect increased when the participants' initial baseline depression severity was dichotomized along a Montgomery-Asberg Depression Rating Scale (MADRS) score of 30. The NSI-189 80-mg dose showed significant benefit over placebo when utilizing the MADRS-6 {P = .046) in the subgroup of patients who were moderately depressed (MADRS <30) but was not significant in patients who were severely depressed (MADRS >30). More pronounced procognitive effects were also observed in the moderate subgroup relative to the severe subgroup or the whole study group, in which 11/36 (31%), 5/36 (14%), or 7/36 (19%) of CogScreen variables significantly improved, respectively. conclusions: These results suggest that NSI-189 is effective as a safe adjunctive therapy, with most compelling antidepressant and procognitive benefits noted in patients with moderate depression.

Original languageEnglish
Pages (from-to)182-196
Number of pages15
JournalAnnals of Clinical Psychiatry
Volume32
Issue number3
StatePublished - Aug 2020
Externally publishedYes

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