Tiagabine for the treatment of generalized anxiety disorder: a randomized, open-label, clinical trial with paroxetine as a positive control.
BACKGROUND
Gamma-aminobutyric acid (GABA) plays a central role in the pathophysiology of anxiety. Tiagabine, a selective GABA reuptake inhibitor, enhances normal GABA tone. This 10-week, randomized, open-label trial evaluated tiagabine in patients with generalized anxiety disorder (GAD), with paroxetine serving as a positive control.


METHODS
Adult patients with DSM-IV GAD were randomly assigned to receive either tiagabine or paroxetine. Tiagabine was initiated at 4 mg/day (2 mg morning and evening) during week 1. Between weeks 2 and 6, the dose was individually titrated in 2-mg increments (maximum increase of 4 mg/week) for optimal response to a maximum dose of 16 mg/day (8 mg morning and evening). During weeks 7 through 10, patients received the dosage determined during the titration period. Paroxetine was initiated at 20 mg nightly for the first week and similarly titrated in 10-mg increments to a maximum dose of 60 mg/day. Assessments included the Hamilton Rating Scale for Anxiety (HAM-A), Hospital Anxiety and Depression Scale (HADS), Hamilton Rating Scale for Depression (HAM-D), Pittsburgh Sleep Quality Index (PSQI), and Sheehan Disability Scale (SDS).


RESULTS
Forty patients were enrolled (tiagabine, N = 20; paroxetine, N = 20). Mean final doses were tiagabine 10 mg/day (range, 4-16 mg/day) or paroxetine 27 mg/day (range, 20-40 mg/day). Tiagabine and paroxetine significantly reduced anxiety (HAM-A and HADS total and anxiety subscales). Although patients were not diagnosed with a mood disorder, both tiagabine and paroxetine reduced comorbid depressive symptoms (HAM-D total and HADS total and depressive subscale). Tiagabine and paroxetine significantly improved sleep quality (PSQI) and functioning (SDS). Both tiagabine and paroxetine were well tolerated.


CONCLUSIONS
The selective GABA reuptake inhibitor tiagabine and the positive control paroxetine significantly reduced anxiety and comorbid depressive symptoms, improved sleep quality and functioning, and were well tolerated in patients with GAD. Tiagabine may be a therapeutic option for the treatment of anxiety disorders.
Rosenthal
Murray
M
BMR HealthQuest, 3625 Ruffin Road, Suite 100, San Diego, CA 92123, USA. rosenthal@bmrhealthquest.com
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; 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*; D017374:Paroxetine / Q000009:adverse effects / Q000627:therapeutic use*; D010555:Personality Inventory; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012890:Sleep / Q000187:drug effects; D000078308:Tiagabine; D016896:Treatment Outcome
D000927:Anticonvulsants; D018687:Antidepressive Agents, Second-Generation; D018755:GABA Agonists; D009557:Nipecotic Acids; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000078308:Tiagabine