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.

Pharmacotherapy of Fibromyalgia: Focus on Duloxetine

“…48 These doses may be useful in depression or anxiety, for example with 18.28% patients taking 120 mg/day in a general anxiety disorder study with flexible dosing. 49 In cases of efficacious dosing, in agreement with the presented studies, it is possible to stop duloxetine after 3 to 6 months, and eventually 12 months. 33 After this period of remission, the dose may be gradually decreased, with regular assessments.…”

Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review

“…There were 22 double-blind RCT (online suppl. As for duloxetine, 1 study [8] reported a significantly greater incidence of discontinuation-emergent adverse events (DEAE) in duloxetine-treated patients compared to placebo, whereas 2 trials did not [9,10].…”

“…In the RCT that reported data about the comparison between SNRI and placebo, withdrawal symptoms were significantly higher after discontinuation of venlafaxine [11,12,19,22] and desvenlafaxine [15,16,23,34], whereas they did not differ from placebo in most of the trials on duloxetine [9,10,17,22,[24][25][26]33] or in the studies on levomilnacipran [14] and milnacipran [13]. The duration of treatment with venlafaxine or desvenlafaxine was as short as 2 months [11,15,16,23].…”

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

“…In one of these studies, venlafaxine was superior to placebo, whereas in the second trial the difference to placebo could not be demonstrated on the primary efficacy measure, but only on some secondary outcome measures (A). Á Duloxetine was more effective than placebo in DBPC studies (Koponen et al 2007;Rynn et al 2007aRynn et al , 2008. Also, in three-arm studies, both duloxetine and the comparator venlafaxine were better than placebo (Hartford et al 2007;Nicolini et al 2008).…”