Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: A 6-month randomized controlled trial.
BACKGROUND
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.


METHODS
Six-month, randomized, double-blind, placebo-controlled, parallel-group trial conducted May 1996 to October 1997.


METHODS
Fourteen outpatient clinics and private psychiatric practices in the United States.


METHODS
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.


METHODS
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.


METHODS
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.
Gelenberg
A J
AJ
Arizona Health Sciences Center, Department of Psychiatry, 1501 N Campbell, PO Box 245002, Tucson, AZ 85724-5002. alang@u.arizona.edu
Lydiard
R B
RB
Rudolph
R L
RL
Aguiar
L
L
Haskins
J T
JT
Salinas
E
E
D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D010045:Outpatients; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D000069470:Venlafaxine Hydrochloride
D014151:Anti-Anxiety Agents; D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D000069470:Venlafaxine Hydrochloride