title: A randomized, double-blind study comparing LY2216684 and placebo in the treatment of major depressive disorder.
abstract: The efficacy, tolerability, and safety of LY2216684, a highly selective norepinephrine reuptake inhibitor, were studied in adult patients with major depressive disorder (MDD). This randomized, double-blind study compared flexible-dose LY2216684 6-18 mg once daily (N = 250) with placebo (N = 245) for 10 weeks acute therapy followed by 1 year LY2216684 treatment (results not reported here). Primary inclusion criteria consisted of GRID 17-item Hamilton Rating Scale for Depression total score ≥18 and Clinical Global Impressions-Severity score ≥4. The primary efficacy measure was the Montgomery-Asberg Depression Rating Scale (MADRS) total score. Response was defined as a ≥50% reduction in MADRS score and remission as MADRS total score ≤10. Global functioning was assessed using the Sheehan Disability Scale (SDS). LY2216684-treated patients showed significant improvement from baseline on the MADRS total score compared with placebo-treated patients (-13.3 vs. -9.8, p < .001), and they had a significantly higher probability of achieving response (49.5%) and remission (29.7%) compared with placebo-treated patients (29.3% and 18.8%, respectively). For the SDS global functional impairment score, LY2216684 treatment resulted in significantly greater improvement compared with placebo treatment (p < .001). More LY2216684-treated than placebo-treated patients discontinued from the study because of an adverse event or death (9.6% vs. 1.6%, p ≤ .001). LY2216684 was associated with significant increases (p < .01) from baseline in systolic (3 mm Hg) and diastolic (4 mm Hg) blood pressure and pulse (10 bpm) compared with placebo. LY2216684 6-18 mg demonstrated significant efficacy and was tolerated in the treatment of MDD.
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. pangallo_beth_a@lilly.com
authors.forename: Beth
authors.initials: B
authors.lastname: Pangallo
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Dellva
authors.forename: Deborah N
authors.initials: DN
authors.lastname: D'Souza
authors.forename: Beal
authors.initials: B
authors.lastname: Essink
authors.forename: James
authors.initials: J
authors.lastname: Russell
authors.forename: Celine
authors.initials: C
authors.lastname: Goldberger
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000188:drug therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage* / Q000009:adverse effects*; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D009025:Morpholines; C568831:alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol; D010626:Phenylethyl Alcohol