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 ≥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. Depression and Anxiety 0:1–8, 2007.