To assess the impact of high levels of insomnia on response to pregabalin (PGB) in patients with GAD.

Pooled data were analyzed from 6 double-blind, placebo-controlled, 4- to 6-week trials of outpatients who met DSM-IV criteria for GAD with a minimum Hamilton rating scale for anxiety (HAM-A) score ≥18. Response was evaluated for 3 fixed-dose PGB groups: 150mg/d, 300-450mg/d, and 600mg/d. A "high-insomnia" subgroup was defined by a baseline HAM-D insomnia factor score ≥4 (maximum=6).

At baseline, 482 (31%) patients met criteria for the high-insomnia subgroup, and 1073 (69%) for the low-insomnia subgroup. Mean baseline HAM-A scores were non-significantly higher (approx. 1-point) in high-insomnia vs low-insomnia patients. In high-insomnia patients, PGB produced significantly greater improvement in HAM-A total scores at LOCF-endpoint vs placebo—PGB 150mg/d (-10.3±1.01), PGB 300-450mg/d (-12.4±0.88), PGB 600mg/d (-11.6±0.72), and placebo (-8.4±0.66) (P<0.0001, all comparisons). Effect sizes for endpoint HAM-A change were higher in high-insomnia than low-insomnia subgroups (0.47 vs 0.32). Endpoint HAM-A-score changes were the same (-12.0) on PGB in both insomnia subgroups; placebo response was higher in low-insomnia patients. Significantly more high-insomnia patients on PGB were insomnia responders (reduction to minimal-to-no insomnia) (75.2%, all doses combined) vs placebo (61.5%; P<0.005). Rates of treatment-emergent insomnia were 4.7% for all PGB doses combined vs 5.4% for placebo.

Pregabalin was well tolerated, and improved overall anxiety symptoms, while specifically improving insomnia in patients with GAD presenting with high levels of concurrent insomnia.