Open-Label Tiagabine Monotherapy for Major Depressive Disorder With Anxiety

Linda L. Carpenter, M.D.; Jordan M. Schecter, M.D.; Audrey R. Tyrka, M.D., Ph.D.; Andrea F. Mello, M.D.; Marcelo F. Mello, M.D.; Ryan Haggarty, M.A.; and Lawrence H. Price, M.D.

Objective: Gamma-aminobutyric acid (GABA) plays a key role in the pathophysiology and treatment of depression and anxiety. Tiagabine, a selective GABA reuptake inhibitor (SGRI) that enhances normal GABA tone, was evaluated for its efficacy and safety in the treatment of depression comorbid with significant anxiety.

Method: In this 8-week, single-center, open-label study, adults with DSM-IV-diagnosed major depressive disorder and significant anxiety (i.e., "anxious depression") received tiagabine monotherapy, initiated at 4 mg/day and titrated for optimum response as tolerated to a maximum dose of 20 mg/day. Symptoms, function, and adverse events were assessed at regular intervals. Patients were entered from April 2002 to February 2003.

Results: Nineteen patients entered the study and 15 met criteria for intent-to-treat analyses. Of those, 6 (40%) discontinued treatment and 9 (60%) completed the 8-week protocol. Tiagabine significantly improved depression, as shown by a reduction in mean ± SD Hamilton Rating Scale for Depression scores from baseline (31.9 ± 6.1) to endpoint (17.0 ± 12.4; p = .002). Categorical response rate was 47% (N = 7). Tiagabine also significantly improved anxiety (Hamilton Rating Scale for Anxiety baseline score of 22.7 ± 4.9 vs. endpoint score of 12.5 ± 8.8; p=.002). The mean±SD final daily dose was 12.8 ± 5.8 mg. The most commonly reported adverse events were dizziness, headache, and gastrointestinal upset/nausea.

Conclusion: These results suggest the potential of the SGRI tiagabine in the treatment of depression with anxiety. Large, placebo-controlled trials are needed.

(J Clin Psychiatry 2006;67:66-71)

Received May 17, 2005; accepted Nov. 14, 2005. From the Mood Disorders Research Program, Butler Hospital and the Department of Psychiatry and Human Behavior, Brown Medical School, Providence, R.I.

This investigator-initiated study was funded by a grant from Cephalon, Inc., West Chester, Pa.

This material concerns an indication for tiagabine (Gabitril) that has not been reviewed by the U.S. Food and Drug Administration.

Data were presented in poster form at the 58th Annual Meeting of the Society of Biological Psychiatry, May 15-17, 2003, San Francisco, Calif., and the 156th Annual Meeting of the American Psychiatric Association, May 17-22, 2003, San Francisco, Calif.

Financial disclosure appears at the end of this article.

The authors wish to thank Julia Burke, M.S.N., for clinical care of study subjects, Kathleen Reilly, M.S., for her assistance in the analysis of data, and Patric DelCioppo, B.A., for his help preparing the figures and tables.

Corresponding author and reprints: Linda L. Carpenter, M.D., Butler Hospital, 345 Blackstone Blvd., Providence, RI 02906 (e-mail: Linda_Carpenter_MD@Brown.edu).