Tiagabine in adult patients with generalized anxiety disorder: results from 3 randomized, double-blind, placebo-controlled, parallel-group studies.
The objective of these studies was to evaluate the efficacy and tolerability of tiagabine, a selective gamma-aminobutyric acid reuptake inhibitor, in adult patients with generalized anxiety disorder (GAD). Patients with a diagnosis of GAD were enrolled in 1 of 3 randomized, placebo-controlled, 10-week studies. In each study, tiagabine was taken twice daily in divided doses--4, 8, or 12 mg/d in a fixed-dose study and 4-16 mg/d in two flexible-dose trials. The primary efficacy measure was the change from baseline in the 14-item Hamilton Rating Scale for Anxiety (HAM-A) total score at the final visit (last observation carried forward). Additional measures included change from baseline in the anxiety subscale of the Hospital Anxiety and Depression Scale, the Sheehan Disability Scale, and Clinical Global Impressions-Improvement scale. Tolerability was assessed via spontaneous reports as well as rating scales throughout the study period. In all 3 studies, there was no significant differentiation from placebo on the primary measure (change in HAM-A) for any tiagabine dose (P > 0.05). In the 2 flexible-dose studies, the tiagabine group showed improvements over time in the HAM-A that reached significance only in those patients who completed 10 weeks of treatment (study 2, P = 0.018; study 3, P = 0.036). The most common adverse events were dizziness, headache, nausea, fatigue, and somnolence. In conclusion, the results of these studies do not support the efficacy of tiagabine in adult patients with GAD.
Pollack
Mark H
MH
Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA. mpollack@partners.org
Tiller
Jane
J
Xie
Fang
F
Trivedi
Madhukar H
MH
D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018755:GABA Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D010555:Personality Inventory; D016032:Randomized Controlled Trials as Topic; D000078308:Tiagabine; D016896:Treatment Outcome
D014151:Anti-Anxiety Agents; D018755:GABA Agonists; D009557:Nipecotic Acids; D000078308:Tiagabine