title: A study of the effects of LY2216684, a selective norepinephrine reuptake inhibitor, in the treatment of major depression.
abstract: The current study sought to test the efficacy and safety of the novel selective norepinephrine reuptake inhibitor LY2216684 compared to placebo in patients with major depressive disorder (MDD). Escitalopram was used as a control for assay sensitivity. Adult outpatients with MDD, confirmed at screening by the Mini International Neuropsychiatric Interview, a Self-Rated Quick Inventory of Depressive Symptomatology (QIDS-SR) score of at least 12 and a Clinical Global Impression-Severity Score of at least 4, were randomly assigned to LY2216684 (N=269), placebo (N=138), or escitalopram (N=62). Efficacy, safety, and tolerability outcomes were compared during 8 weeks of double-blind treatment. LY2216684 plasma concentrations were measured. LY2216684 did not show statistically significant improvement from baseline compared to placebo in the primary analysis of the Hamilton depression rating scale (HAM-D(17)) total score. Escitalopram demonstrated significant improvement compared to placebo on the HAM-D(17) total score, suggesting adequate assay sensitivity. Both LY2216684 and escitalopram showed statistically significant improvement from baseline on the patient-rated QIDS-SR total score compared to placebo. Headache, nausea, constipation, dry mouth, and insomnia were the most frequently reported adverse events in the LY2216684 group. A 3-6 beats per minute mean increase from baseline in pulse rate was observed in the LY2216684 group. LY2216684 plasma concentrations increased as the dose increased from 3 mg to 12 mg. The results of this initial investigation of LY2216684's efficacy suggest that it may have antidepressant potential. More definitive data to confirm this is necessary. Its safety profile does not preclude further clinical development.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. dube_sanjay@lilly.com
authors.forename: Sanjay
authors.initials: S
authors.lastname: Dubé
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Dellva
authors.forename: Marcia
authors.initials: M
authors.lastname: Jones
authors.forename: William
authors.initials: W
authors.lastname: Kielbasa
authors.forename: Robert
authors.initials: R
authors.lastname: Padich
authors.forename: Amitabh
authors.initials: A
authors.lastname: Saha
authors.forename: Prasad
authors.initials: P
authors.lastname: Rao
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010045:Outpatients; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D012720:Severity of Illness Index; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D016896:Treatment Outcome; D014987:Xerostomia / Q000139:chemically induced; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors