Gabapentin and Tiagabine for Social Anxiety

Abstract

Sir: Social anxiety disorder is characterized by fear and avoidance of social situations in which patients may feel scrutinized and considered foolish by others.1 Social anxiety disorder can significantly impair educational, social, occupational, and physical functioning.2 Selective serotonin reuptake inhibitors have been the first line of treatment, but only a modest remission rate has been noted.2 Selective serotonin reuptake inhibitors have gastrointestinal, activating, and sexual side effects that limit their utility. Benzodiazepines have been the second-line treatment for social anxiety disorder, mainly due to their potential for dependence and abuse.3 Two newer drugs, tiagabine and gabapentin, have been used in the treatment of anxiety disorders.4–6 Tiagabine is a highly selective inhibitor of the γ-aminobutyric acid (GABA) transporter system (GAT-1).4 Gabapentin is a mixed-type inhibitor of GABA transaminase.7 A small study was conducted at Eastern Virginia Medical School, Department of Psychiatry, in Norfolk, Va. from 2005 through 2007 after approval by the institutional review board that looked at the effectiveness of these 2 drugs in social anxiety disorder. Method. Participants were 8 adults aged 21 to 39 years (mean, 26.5): 5 men and 6 white subjects, 1 black subject, and 1 Asian subject. Inclusion criteria were subjects who were aged 18 to 65 years, male or female, generally healthy, able to provide informed consent, and diagnosed with social anxiety disorder, which was confirmed by DSM-IV criteria and a Liebowitz Social Anxiety Scale (LSAS)8 score greater than 30. Participants were excluded if they had another current Axis I psychiatric disorder, had a major medical illness, were taking medications that interacted with the study drugs, were actively using alcohol or illegal drugs, or were pregnant, planning to become pregnant, or breastfeeding. The study was a randomized, double-blind, crossover design of 4 to 5 months’ duration. Subjects had a washout period of 2 weeks if they were taking any medication for social anxiety disorder. They received a physical exam, a complete blood count, and a comprehensive metabolic panel. When patients successfully completed this phase, they were then randomly assigned to either tiagabine or gabapentin. Subjects had a 2-week titration to the full dosage of treatment arm A medication prior to a four-week stable dosage regimen. A 2-week washout period occurred between treatment arms. Treatment arm B included a 2-week titration and a 4-week stable dosage regimen. Patients were seen for a final visit 2 weeks after stopping study medication. The full daily doses were 2400 mg for tiagabine and 1800 mg for gabapentin. During each visit, the subject completed the LSAS, one of the most commonly used instruments for assessing social anxiety disorder.9,10 Results. Seven subjects had an initial LSAS score in the severe range, with 1 subject in the moderate range. All subjects with severe social anxiety disorder responded well to either anticonvulsant, with 2 subjects (1 for each study drug) reaching remission (LSAS < 30). On the LSAS total score, 4 subjects (2 receiving tiagabine and 2 receiving gabapentin) had clinically significant change (20 points). Patients reported very few side effects, with sedation and mild dizziness being the most common. It appears that both gabapentin and tiagabine can be effective in reducing symptoms of social anxiety disorder as measured by the LSAS. Both medications were well tolerated, with only 1 person stopping gabapentin secondary to sedation. This small study adds to the existing database stating that the anticonvulsants gabapentin and tiagabine can be efficacious in the treatment of social anxiety disorder, with a favorable side effect profile compared to the selective serotonin reuptake inhibitor and benzodiazepine treatment choices. Maria R. Urbano, M.D. David R. Spiegel, M.D. Nena Laguerta, M.D. Catherine J. Shrader, B.S. Daniel F. Rowe, B.S. Liana F. Hategan, M.D. Department of Psychiatry, Eastern Virginia Medical School, Norfolk, Virginia