title: Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial.
abstract: Generalized anxiety disorder (GAD), a prevalent and chronic illness, is associated with dysregulation in both serotonergic and noradrenergic neurotransmission. Our study examined the efficacy, safety, and tolerability of duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, for short-term treatment of adults with GAD. In a 10-week, double-blind, progressive-titration, flexible-dose trial, 327 adult outpatients with a DSM-IV-defined GAD diagnosis were randomized to duloxetine 60-120 mg (DLX, N=168) or placebo (PLA, N=159) treatment. The primary efficacy measure was mean change from baseline to endpoint in Hamilton Anxiety Scale (HAMA) total score. Secondary outcome measures included response rate (HAMA total score reduction > or =50% from baseline), Clinician Global Impression-Improvement (CGI-I) scores, and Sheehan Disability Scale (SDS) scores. Patients who received duloxetine treatment demonstrated significantly greater improvement in HAMA total scores (P=.02); a higher response rate (P=.03), and greater improvement (P=.04) than patients who received placebo. Duloxetine-treated patients were also significantly more improved than placebo-treated patients on SDS global functional (P<.01) and work, social, and family/home impairment scores (P<.05). The rate of discontinuation due to adverse events (AEs) was higher for the duloxetine group compared with the placebo group (P=.002). The AEs most frequently associated with duloxetine were nausea, dizziness, and somnolence. Duloxetine was an efficacious, safe, and well-tolerated treatment that resulted in clinically significant improvements in symptom severity and functioning for patients with GAD.
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Moira
authors.initials: M
authors.lastname: Rynn
authors.forename: James
authors.initials: J
authors.lastname: Russell
authors.forename: Janelle
authors.initials: J
authors.lastname: Erickson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Detke
authors.forename: Susan
authors.initials: S
authors.lastname: Ball
authors.forename: Jeff
authors.initials: J
authors.lastname: Dinkel
authors.forename: Karl
authors.initials: K
authors.lastname: Rickels
authors.forename: Joel
authors.initials: J
authors.lastname: Raskin
mesh_terms: D000328:Adult; D000553:Ambulatory Care; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000139:chemically induced; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D010919:Placebos; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride