The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study

J Clin Psychiatry. 2005 Nov;66(11):1401-8. doi: 10.4088/jcp.v66n1109.


Objective: To evaluate the efficacy and tolerability of tiagabine, a selective gamma-aminobutyric acid (GABA) reuptake inhibitor, in adults with generalized anxiety disorder (GAD).

Method: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / psychology
  • Data Interpretation, Statistical
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurotransmitter Uptake Inhibitors / therapeutic use*
  • Nipecotic Acids / adverse effects
  • Nipecotic Acids / therapeutic use*
  • Outcome Assessment, Health Care / statistics & numerical data
  • Placebos
  • Psychiatric Status Rating Scales
  • Tiagabine
  • Treatment Outcome
  • gamma-Aminobutyric Acid / physiology*


  • Neurotransmitter Uptake Inhibitors
  • Nipecotic Acids
  • Placebos
  • gamma-Aminobutyric Acid
  • Tiagabine