Tiagabine for posttraumatic stress disorder: effects of open-label and double-blind discontinuation treatment.

Rationale: Preliminary results suggest a potential benefit of agents that enhance gamma-aminobutyric acid (GABA) neurotransmission in treating posttraumatic stress disorder (PTSD).

Objectives: It is the aim of this study to evaluate the effect of a selective GABA reuptake inhibitor (SGRI), tiagabine, in patients with PTSD.

Methods: Twenty-nine adult outpatients with PTSD were treated with open-label tiagabine for 12 weeks. Those who responded to treatment (i.e., demonstrated at least minimal clinical improvement) were randomly assigned to double-blind treatment with either tiagabine or matching placebo. Efficacy assessments included measures of PTSD, anxiety, depression, sleep quality, resilience, and disability. Safety evaluation included changes in vital signs and weight and treatment-emergent adverse events.

Results: In subjects completing open-label treatment (n=19), significant improvement was observed on all outcome measures (P<0.05) and the treatment was well tolerated. Eighteen subjects responded and were randomized into the double-blind phase. Following randomization, benefits of treatment were generally upheld, but there was no greater incidence of relapse in the placebo group. However, continued treatment with tiagabine was associated with a greater trend toward likelihood of remission than if one was switched to placebo (P<0.08).

Conclusions: These findings suggest a possible role for the SGRI tiagabine in the treatment of PTSD. As the role of GABAergic drugs in PTSD is poorly defined, larger, randomized, double-blind, placebo-controlled trials are needed.