The objective of the study was to evaluate the response of generalized
anxiety disorder (GAD) patients with prominent gastrointestinal (GI) symptoms to
pregabalin (
PGB) treatment. Data were pooled from six double-blind, placebo (PBO)-controlled, 4-6 week trials in outpatients who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria for GAD with a minimum Hamilton Anxiety Rating Scale (HAM-A) total score of 20. Treatment response was evaluated for three
PGB fixed-dosage groups: 150, 300-450, and 600 mg/day, and for fixed doses of a
benzodiazepine (
alprazolam, 1.5 mg/day;
lorazepam, 6 mg/day). A GI-high subgroup (high GI symptomatology) was defined by a baseline HAM-A item-11 (GI) score of 3 or greater (severe/very severe). At baseline, 301 patients (16.2%) met criteria for the GI-high subgroup. Baseline characteristics were approximately similar for the four study treatments in the GI-high subgroup. For the GI-high subgroup, last observation carried forward (LOCF) endpoint reduction in HAM-A was significantly higher on
PGB-300/450 -13.8+/-1.2 and PGB-600 -14.7+/-1.0 compared with PBO -10.1+/-0.9 (P<0.01 for both comparisons); but the difference on PGB-150 did not achieve significance (-13.5+/-1.6; P=0.083). Also in the GI-high subgroup, endpoint reduction in HAM-A item-11 was significantly higher on
PGB-300/450 compared with PBO (-1.93+/-0.16 vs. -1.52+/-0.13; P=0.04), but did not achieve significance on PGB-600 mg (-1.89+/-0.14; P=0.06), or PGB-150 mg (-1.90+/-0.23; P=0.16). In the GI-high subgroup, treatment with a
benzodiazepine was not associated with significant endpoint reduction in either the HAM-A total score or the HAM-A item-11 score. Patients in the GI-high subgroup had higher discontinuation rates when treated with
benzodiazepines, whereas treatment with
PGB 300-600 mg/day was not associated with treatment-emergent worsening in GI symptoms compared with placebo. Treatment with
PGB improved overall levels of anxiety, as well as specifically improving GI symptoms.