A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder.
Pregabalin is a novel compound under development for the treatment of several types of anxiety disorders. To obtain an initial evaluation of the efficacy and safety of pregabalin in the treatment of generalized anxiety disorder (GAD), we conducted a double-blind, fixed-dose, parallel-group, placebo and active-controlled multicenter 4-week study that compared 271 patients randomized to receive pregabalin 50 mg tid (N = 70), pregabalin 200 mg tid (N = 66), placebo (N = 67), or lorazepam 2 mg tid (N = 68), followed by a 1-week double-blind taper. The primary efficacy parameter was change from baseline to endpoint (last observation carried forward) in the Hamilton Anxiety Scale (HAM-A) total score; adjusted mean change scores on the HAM-A were significantly improved for pregabalin 200 mg tid (difference of 3.90 between drug and placebo; p = 0.0013 [ANCOVA], df = 252) and for lorazepam (difference of 2.35; p = 0.0483 [ANCOVA], df = 252), with the significant difference between the pregabalin 200 mg tid and placebo groups seen at week 1 of treatment (p = 0.0001 [ANCOVA], df = 238). Safety analysis, which included assessment of spontaneously reported adverse events, laboratory monitoring, and withdrawal symptoms, showed pregabalin to be generally well-tolerated. The most common adverse events seen with pregabalin 200 mg tid were somnolence and dizziness. They were usually mild or moderate in intensity and were often transient. Pregabalin-treated patients had a higher completion rate than lorazepam-treated patients. This study supports the hypothesis that pregabalin is effective and safe in short-term therapy for GAD. More studies are needed to determine the best dosing regimen to optimize efficacy and tolerability.
Feltner
Douglas E
DE
Pfizer Global Research and Development, Ann Arbor Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. Douglas.Feltner@pfizer.com
Crockatt
Jerri G
JG
Dubovsky
Steven J
SJ
Cohn
Cal K
CK
Shrivastava
Ram K
RK
Targum
Steven D
SD
Liu-Dumaw
Maria
M
Carter
Cathryn M
CM
Pande
Atul C
AC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000523:psychology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*
D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid