CONTEXT: Generalized anxiety disorder (GAD) is a chronic disorder that is associated with debilitating psychic and somatic symptoms. Venlafaxine extended-release (XR) capsules have been shown to be effective in short-term treatment of patients with GAD without major depressive disorder (MDD), but long-term data are needed to establish whether this agent confers persistent benefits. OBJECTIVE: To compare the 6-month efficacy and safety of a flexible dosage of venlafaxine XR in outpatients with GAD without associated MDD. DESIGN: Six-month, randomized, double-blind, placebo-controlled, parallel-group trial conducted May 1996 to October 1997. SETTING:Fourteen outpatient clinics and private psychiatric practices in the United States. PARTICIPANTS: A total of 251 outpatients aged 18 years or older who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for GAD, had sufficient symptoms to require treatment, and did not have coexisting MDD. INTERVENTIONS: Participants were randomly assigned to receive either placebo (n=127) or venlafaxine XR (75, 150, or 225 mg/d, as required to control symptoms; n=124) for 28 weeks. MAIN OUTCOME MEASURES: Changes from baseline in the Hamilton Rating Scale for Anxiety (HAM-A) total score, the HAM-A psychic anxiety factor score, and the Clinical Global Impressions (CGI) scale Severity of Illness and Global Improvement scores, compared by intervention group. RESULTS: During weeks 6 through 28, response rates in the venlafaxine XR group were 69% or higher compared with rates of 42% to 46% in the placebo group (P<.001). By an evaluable-patient analysis, venlafaxine XR compared with placebo significantly improved anxiety scores from week 1 or 2 through week 28 on all primary efficacy measures, including the HAM-A total (P<.001), the HAM-A psychic anxiety factor (P<.001), and the CGI scale scores (P<.001). Adjusted mean changes from baseline to week 28 using last-observation-carried-forward methods were for HAM-A, venlafaxine XR -13.4, placebo -8.7 (P<.001); for HAM-A psychic anxiety score, venlafaxine XR -7.4, placebo -4.2 (P<.001); and for CGI-Improvement, venlafaxine XR 2.2, placebo 3.0 (P<.001). The most common treatment-emergent adverse event was nausea, followed by somnolence and dry mouth. CONCLUSIONS: This study is the first placebo-controlled demonstration of the long-term efficacy of any drug class in treating outpatients with DSM-IV-diagnosed GAD. Venlafaxine XR is an effective, rapidly acting, safe, once-daily agent for both the short- and long-term treatment of anxiety and may provide an important alternative to currently available anxiolytics. JAMA. 2000.
RCT Entities:
CONTEXT: Generalized anxiety disorder (GAD) is a chronic disorder that is associated with debilitating psychic and somatic symptoms. Venlafaxine extended-release (XR) capsules have been shown to be effective in short-term treatment of patients with GAD without major depressive disorder (MDD), but long-term data are needed to establish whether this agent confers persistent benefits. OBJECTIVE: To compare the 6-month efficacy and safety of a flexible dosage of venlafaxine XR in outpatients with GAD without associated MDD. DESIGN: Six-month, randomized, double-blind, placebo-controlled, parallel-group trial conducted May 1996 to October 1997. SETTING: Fourteen outpatient clinics and private psychiatric practices in the United States. PARTICIPANTS: A total of 251 outpatients aged 18 years or older who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for GAD, had sufficient symptoms to require treatment, and did not have coexisting MDD. INTERVENTIONS:Participants were randomly assigned to receive either placebo (n=127) or venlafaxine XR (75, 150, or 225 mg/d, as required to control symptoms; n=124) for 28 weeks. MAIN OUTCOME MEASURES: Changes from baseline in the Hamilton Rating Scale for Anxiety (HAM-A) total score, the HAM-A psychic anxiety factor score, and the Clinical Global Impressions (CGI) scale Severity of Illness and Global Improvement scores, compared by intervention group. RESULTS: During weeks 6 through 28, response rates in the venlafaxine XR group were 69% or higher compared with rates of 42% to 46% in the placebo group (P<.001). By an evaluable-patient analysis, venlafaxine XR compared with placebo significantly improved anxiety scores from week 1 or 2 through week 28 on all primary efficacy measures, including the HAM-A total (P<.001), the HAM-A psychic anxiety factor (P<.001), and the CGI scale scores (P<.001). Adjusted mean changes from baseline to week 28 using last-observation-carried-forward methods were for HAM-A, venlafaxine XR -13.4, placebo -8.7 (P<.001); for HAM-A psychic anxiety score, venlafaxine XR -7.4, placebo -4.2 (P<.001); and for CGI-Improvement, venlafaxine XR 2.2, placebo 3.0 (P<.001). The most common treatment-emergent adverse event was nausea, followed by somnolence and dry mouth. CONCLUSIONS: This study is the first placebo-controlled demonstration of the long-term efficacy of any drug class in treating outpatients with DSM-IV-diagnosed GAD. Venlafaxine XR is an effective, rapidly acting, safe, once-daily agent for both the short- and long-term treatment of anxiety and may provide an important alternative to currently available anxiolytics. JAMA. 2000.
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