Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam.
BACKGROUND
Pregabalin inhibits release of excess excitatory neurotransmitters, presumably by binding to the alpha2-delta subunit protein of widely distributed voltage-dependent calcium channels in the brain and spinal cord.


OBJECTIVE
To assess the anxiolytic efficacy of pregabalin in patients with generalized anxiety disorder.


METHODS
Double-blind, placebo-controlled, active-comparator trial. Patients were randomized to 4 weeks of treatment with pregabalin, 300 mg/d (n = 91), 450 mg/d (n = 90), or 600 mg/d (n = 89); alprazolam, 1.5 mg/d (n = 93); or placebo (n = 91).


METHODS
Psychiatry research and clinic settings.


METHODS
Outpatients meeting the DSM-IV criteria for generalized anxiety disorder, with a baseline Hamilton Anxiety Rating Scale (HAM-A) total score of 20 or greater.


METHODS
Change from baseline to end point in total HAM-A score in the pregabalin and alprazolam groups compared with the placebo group. The end point response criterion was 50% or greater reduction in the HAM-A total score.


RESULTS
Pregabalin and alprazolam produced a significantly greater reduction in mean +/- SE HAM-A total score at last-observation-carried-forward end point compared with placebo (-8.4 +/- 0.8): pregabalin, 300 mg (-12.2 +/- 0.8, P<.001), 450 mg (-11.0 +/- 0.8, P = .02), and 600 mg (-11.8 +/- 0.8, P = .002), and alprazolam (-10.9 +/- 0.8, P = .02). By week 1 and at last-observation-carried-forward end point, the 3 pregabalin groups and the alprazolam group had significantly (P<.01) improved HAM-A psychic anxiety symptoms compared with the placebo group. Compared with the placebo group, HAM-A somatic anxiety symptoms were also significantly (P<.02) improved by the 300- and 600-mg pregabalin groups, but not by the 450-mg pregabalin (week 1, P = .06; week 4, P = .32) and the alprazolam groups (week 1, P = .21; week 4, P = .15). Of the 5 treatment groups, the 300-mg pregabalin group was the only medication group that differed statistically in global improvement at treatment end point not only from the placebo group but also from the alprazolam group.


CONCLUSIONS
Pregabalin was significantly more efficacious than placebo for the treatment of psychic and somatic symptoms of generalized anxiety disorder and was well tolerated by most study patients.
Rickels
Karl
K
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-3309, USA. krickels@mail.med.upenn.edu
Pollack
Mark H
MH
Feltner
Douglas E
DE
Lydiard
R Bruce
RB
Zimbroff
Daniel L
DL
Bielski
Robert J
RJ
Tobias
Kathy
K
Brock
Jerri D
JD
Zornberg
Gwen L
GL
Pande
Atul C
AC
D000328:Adult; D000525:Alprazolam / Q000009:adverse effects / Q000627:therapeutic use; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000627:therapeutic use; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D000069583:Pregabalin; D011569:Psychiatric Status Rating Scales; D012890:Sleep / Q000187:drug effects; D016896:Treatment Outcome; D014987:Xerostomia / Q000139:chemically induced; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D010919:Placebos; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000525:Alprazolam