The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study.
OBJECTIVE
To evaluate the efficacy and tolerability of tiagabine, a selective gamma-aminobutyric acid (GABA) reuptake inhibitor, in adults with generalized anxiety disorder (GAD).


METHODS
This 8-week, randomized, double-blind, multicenter, placebo-controlled study enrolled patients with GAD (DSM-IV). Tiagabine was initiated at 4 mg/day and then flexibly dosed twice a day to a maximum dose of 16 mg/day. Study drug was tapered after week 8 in decrements of 2 mg every other day. Efficacy assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and Sheehan Disability Scale. Adverse events, sexual functioning, and change in depressive symptoms were monitored. Data were collected from May 2003 to January 2004.


RESULTS
A total of 266 patients (tiagabine, N = 134; placebo, N = 132) were included in safety analyses; 260 patients (tiagabine N = 130; placebo N = 130) were included in efficacy analyses. Tiagabine reduced symptoms of GAD according to the observed case and mixed models repeated-measures (MMRM) analyses but not the primary last-observation-carried-forward (LOCF) analysis. At final visit, the reduction from baseline in mean HAM-A total score was 11.8 for tiagabine, compared with 10.2 for placebo (LOCF analysis, p = .27). In a post hoc MMRM analysis, a significant difference in the mean reduction in HAM-A total score over the efficacy evaluation period was found, favoring tiagabine over placebo (p < .01). Tiagabine had an early onset of effect, as shown by significant reduction from baseline in mean HAM-A total score compared with placebo at week 1 (observed cases, p < .05). Tiagabine was generally well tolerated and not associated with changes in sexual functioning or depressive status. Symptoms of a discontinuation syndrome during taper were not observed.


CONCLUSIONS
The primary LOCF analysis was negative; however, results from the observed case and MMRM analyses suggest that tiagabine may be a useful treatment option for adult patients diagnosed with GAD. These findings warrant further evaluation in randomized clinical studies.
Pollack
Mark H
MH
Anxiety Disorders Program, Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA. mpollack@partners.org
Roy-Byrne
Peter P
PP
Van Ameringen
Michael
M
Snyder
Heather
H
Brown
Charles
C
Ondrasik
John
J
Rickels
Karl
K
D000328:Adult; D000368:Aged; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014179:Neurotransmitter Uptake Inhibitors / Q000627:therapeutic use*; D009557:Nipecotic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D000078308:Tiagabine; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D010919:Placebos; D005680:gamma-Aminobutyric Acid; D000078308:Tiagabine