title: Assessment of the Efficacy and Safety of BMS-820836 in Patients With Treatment-Resistant Major Depression: Results From 2 Randomized, Double-Blind Studies.
abstract: Two phase 2B, randomized, double-blind studies assessed the efficacy and safety of fixed or flexible dose of triple monoamine uptake inhibitor BMS-820836 in patients with treatment-resistant depression to demonstrate whether switching to BMS-820836 was superior to the continuation of standard antidepressant treatment. Patients with a history of inadequate response to 1 to 3 adequate trials of antidepressant therapies were prospectively treated with duloxetine 60 mg/d for 8 weeks (CN162-006) or duloxetine 60 mg/d or escitalopram 20 mg/d for 7 weeks (CN162-007). Inadequate responders were randomized to continue their prospective phase treatment or switch to flexible-dose (0.5-2 mg/d; CN162-006) or fixed-dose (0.25, 0.5, 1, or 2 mg/d; CN162-007) BMS-820836 for 6 weeks. The primary end point in both studies was mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from randomization to study end point. BMS-820836 flexible (0.5-2 mg/d) or fixed dose of 1 mg/d or greater showed efficacy similar to the continuation of antidepressant treatment, with no statistically significant or clinically meaningful differences. In the CN162-006 study, the adjusted mean (SE) change in MADRS total score was -8.7 (0.661) and -8.1 (0.656) for BMS-820836 and duloxetine, respectively (P = 0.526). In the CN162-007 study, the adjusted mean (SE) change in MADRS total score was -7.3 (0.830) and -6.6 (0.842) for BMS-820836 of 1 and 2 mg, respectively, and -6.9 (0.602) for the continuation group (P = 0.910). Thus, BMS-820836 was well tolerated, with no evidence of dose-dependent discontinuations due to adverse events, but it failed to demonstrate superiority to the continuation of an existing antidepressant in patients with treatment-resistant depression.
authors.affiliation: From *Bristol-Myers Squibb Company, Wallingford, CT; †Bristol-Myers Squibb Company, Braine-l'Alleud, Belgium; ‡Emory University, Atlanta, GA; §Baylor College of Medicine, Houston, TX; ∥Northwest Clinical Research Center, Bellevue, WA; ¶Department of Psychiatry, Duke University School of Medicine, Durham; #Department of Psychiatry, Duke University Medical Center, Durham; **Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC; ††University of California, San Francisco, CA; ‡‡University of Alabama at Birmingham, Birmingham, AL; and §§University of Pennsylvania, Philadelphia, PA.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Bhagwagar
authors.forename: Anne
authors.initials: A
authors.lastname: Torbeyns
authors.forename: Delphine
authors.initials: D
authors.lastname: Hennicken
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: Boadie W
authors.initials: BW
authors.lastname: Dunlop
authors.forename: Sanjay J
authors.initials: SJ
authors.lastname: Mathew
authors.forename: Arif
authors.initials: A
authors.lastname: Khan
authors.forename: Richard
authors.initials: R
authors.lastname: Weisler
authors.forename: Craig
authors.initials: C
authors.lastname: Nelson
authors.forename: Richard
authors.initials: R
authors.lastname: Shelton
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.forename: Roger
authors.initials: R
authors.lastname: Lane
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D061218:Depressive Disorder, Treatment-Resistant / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D038622:Internationality; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C000594001:6-(2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)pyridazin-3-amine; D007546:Isoquinolines; D011724:Pyridazines