TY - JOUR
T1 - NSI-189 phosphate, a novel neurogenic compound, selectively benefits moderately depressed patients
T2 - A post-hoc analysis of a phase 2 study of major depressive disorder
AU - Johe, Karl K.
AU - Kay, Gary
AU - Kumar, Santosh
AU - Burdick, Katherine E.
AU - McLntyre, Roger S.
AU - Papakostas, George I.
AU - Fava, Maurizio
N1 - Publisher Copyright:
© 2020 Quadrant Healthcom Inc.. All rights reserved.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85088810911&partnerID=8YFLogxK
M3 - Article
C2 - 32722729
AN - SCOPUS:85088810911
SN - 1040-1237
VL - 32
SP - 182
EP - 196
JO - Annals of Clinical Psychiatry
JF - Annals of Clinical Psychiatry
IS - 3
ER -