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
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