Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine.
OBJECTIVE
Pregabalin has demonstrated robust, rapid efficacy in reducing symptoms of generalized anxiety disorder (GAD) in 4 placebo-controlled clinical trials. The current study compared the efficacy and safety of pregabalin and venlafaxine in patients diagnosed with moderate to severe GAD.


METHODS
The study was conducted from December 21, 1999, to July 31, 2001. Outpatients (N = 421) in primary care or psychiatry settings meeting DSM-IV criteria for GAD were randomly assigned to 6 weeks of double-blind treatment with pregabalin 400 or 600 mg/day, venlafaxine 75 mg/day, or placebo. The primary analysis was change in Hamilton Rating Scale for Anxiety (HAM-A) total score from baseline to last-observation-carried-forward (LOCF) endpoint. Secondary analyses included the change in HAM-A psychic (emotional) and somatic (physical) factor scores, significant improvement at week 1, and week 1 improvement sustained at every visit through endpoint.


RESULTS
Pregabalin at both dosages (400 mg/day, p = .008; 600 mg/day, p = .03) and venlafaxine (p = .03) produced significantly-greater improvement in HAM-A total score at LOCF endpoint than did placebo. Only the pregabalin 400-mg/day treatment group experienced significant improvement in all a priori primary and secondary efficacy measures. Pregabalin in both dosage treatment groups (400 mg/day, p < .01; 600 mg/day, p < .001) significantly improved HAM-A total score at week 1, with significant improvement through LOCF endpoint. Statistically significant improvement began at week 2 for venlafaxine. Discontinuation rates due to associated adverse events were greatest in the venlafaxine treatment group: venlafaxine, 20.4%; pregabalin 400 mg/day, 6.2%; pregabalin 600 mg/day, 13.6%; placebo, 9.9%.


CONCLUSIONS
Pregabalin was safe, well tolerated, and rapidly efficacious across the physical-somatic as well as the emotional symptoms of GAD in the majority of patients studied in primary care and psychiatric settings.
Montgomery
Stuart A
SA
Imperial College School of Medicine, London, UK. Stuart@samontgomery.co.uk
Tobias
Kathy
K
Zornberg
Gwen L
GL
Kasper
Siegfried
S
Pande
Atul C
AC
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003511:Cyclohexanols / Q000009:adverse effects / Q000627:therapeutic use*; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D000069583:Pregabalin; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000927:Anticonvulsants; D003511:Cyclohexanols; D010919:Placebos; D000069583:Pregabalin; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; D005680:gamma-Aminobutyric Acid