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: Beth Pangallo, Mary Anne Dellva, Deborah N D'Souza, Beal Essink, James Russell, Celine Goldberger
• Journal: Journal of psychiatric research (J Psychiatr Res) Vol. 45 Issue 6 Pg. 748-55 (Jun 2011) ISSN: 1879-1379 [Electronic] England
• PMID: 21511276 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Adrenergic Uptake Inhibitors
• Antidepressive Agents
• Morpholines
• alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol
• Phenylethyl Alcohol

Topics

• Adolescent
• Adrenergic Uptake Inhibitors (administration & dosage, adverse effects)
• Adult
• Aged
• Antidepressive Agents (administration & dosage, adverse effects)
• Depressive Disorder, Major (drug therapy)
• Diagnostic and Statistical Manual of Mental Disorders
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Morpholines (administration & dosage, adverse effects)
• Phenylethyl Alcohol (administration & dosage, adverse effects, analogs & derivatives)
• Psychiatric Status Rating Scales
• Treatment Outcome
• Young Adult