An open-label study of tiagabine as augmentation therapy for anxiety.

Background: At least 50% of patients with anxiety disorders experience only partial response to pharmacotherapy and require augmentation therapy. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS, and agents that modulate GABA neurotransmission have shown promise in the treatment of anxiety disorders and are often used as augmentation agents.

Objective: This study evaluated tiagabine, a selective GABA reuptake inhibitor (SGRI), as augmentation therapy.

Methods: This 8-week, open-label study enrolled patients who remained symptomatic despite adequate drug trials for treatment of anxiety symptoms. Tiagabine augmentation therapy was initiated at 4 mg/d (taken in 2 doses; one in the morning with breakfast and one in the evening with a snack) for 2 days and increased to 8 mg/d for 10 days. Dose was then adjusted according to efficacy/tolerability in increments of 2 mg every 3 days up to a maximum of 20 mg/d. Effect was assessed using the Hamilton Rating Scale for Anxiety (HAM-A), Beck Anxiety Inventory (BAI), Clinical Global Impression (CGI) scale, Pittsburgh Sleep Quality Index (PSQI), and 36-item Short-Form Health Survey (SF-36).

Results: Of the 18 patients enrolled, 17 were included in the efficacy analysis; one withdrew due to an adverse event prior to post-baseline assessment. Mean final dose of tiagabine was 13 mg/d. Tiagabine as augmentation therapy further reduced anxiety symptoms, as shown by significant decreases in mean HAM-A total and BAI scores at Week 8 (P<0.001). Thirteen patients (76%) responded (> or =50% reduction in HAM-A total score), and 10 patients (59%) achieved remission (HAM-A total score < or =7) at Week 8. Tiagabine improved sleep quality, with a significant reduction seen in PSQI global score at Week 8 (P=.001). Augmentation therapy with tiagabine was generally well tolerated.

Conclusion: These preliminary findings suggest that the SGRI tiagabine may be an effective and generally well tolerated augmentation therapy in patients with anxiety who remain symptomatic despite adequate drug trials for treatment of anxiety symptoms.