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Generalized anxiety disorder (GAD) is a chronic illness that leads to substantial impairments in quality of life. This post-hoc analysis used combined data from three 8-week quetiapine extended-release trials to investigate the reliability, validity, and responsiveness of the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q (SF)] in 2588 patients with GAD. The baseline Q-LES-Q (SF) score showed a Cronbach's α value of 0.86, indicative of reliability. Validity analyses for Q-LES-Q (SF) identified significant correlations with clinical efficacy measures (r>0.34 at week 8; P<0.001) and significant discrimination between patient groups categorized by symptom severity (P<0.001). Responsiveness was shown by significant differences in mean changes in Q-LES-Q (SF) scores at week 8 between patients defined according to the Hamilton Rating Scale for Anxiety response or remission criteria (P<0.001). The minimum clinically important Q-LES-Q (SF) score change was identified to be 6.80 points. Using this definition, response rates were significantly greater with quetiapine extended-release 150 mg versus placebo in individual trials and the combined population (P≤0.02). This analysis shows the overall reliability, validity, and responsiveness of the Q-LES-Q (SF) as a measure of overall quality of life and satisfaction in patients with GAD.