title: Extended Release Quetiapine Fumarate (Quetiapine XR) as Adjunct Therapy in Patients with Generalized Anxiety Disorder and a History of Inadequate Treatment Response: A Randomized, Double-Blind Study.
abstract: To evaluate the efficacy and tolerability of adjunct extended release quetiapine fumarate (quetiapine XR) in patients with generalized anxiety disorder (GAD) and inadequate response to selective serotonin reuptake inhibitors/ serotonin norepinephrine reuptake inhibitors (SSRI/SNRIs).
  11-week (1-week single-blind placebo run-in; 8-week randomized treatment; 2-week post-treatment period), double-blind, placebo-controlled study. Patients were randomized to quetiapine XR or placebo adjunct to SSRI/SNRI. 50 mg initial dose; 150 mg/day, Day 3; 300 mg/day, Weeks × and 4 if indicated (Clinical Global Impressions-Severity of Illness [CGI-S] ≥ 4; 150 mg/day tolerated). Primary endpoint: change from randomization to Week 8 in HAM-A total score. Secondary variables: Hamilton Rating Scale for Anxiety (HAM-A) psychic/somatic clusters, response and remission; and CGI-S.
  409 patients were randomized to quetiapine XR (n = 209) or placebo (n = 200); 41% and 55% of patients, respectively, had dose increases (300 mg/day). Week 8 mean change in HAM-A total score was not statistically significant for quetiapine XR (-10.74; p = 0.079) versus placebo (-9.61). Secondary variables were generally consistent with the primary analysis, except a significant reduction in HAM-A total score at Week 1 (-6.45, quetiapine XR versus -4.47, placebo; p < 0.001); significant improvements in HAM-A psychic cluster (p < 0.05) and CGI-S total (p < 0.05) scores at Week 8. Adverse events (.10% either group) were dry mouth, somnolence, sedation, headache, and dizziness.
  In patients with GAD and inadequate response to SSRI/SNRI, adjunct quetiapine XR did not show a statistically significant effect for the primary endpoint at Week 8, although some secondary endpoints were statistically significant versus placebo. Quetiapine XR was generally well tolerated.
authors.affiliation: Dr. Khan, MD, Northwest Clinical Research Center, Bellevue, WA; Duke University School of Medicine, Department of Psychiatry and Behavioral Sciences, Durham, NC. Dr. Atkinson, MD, Finger Lakes Clinical Research, Rochester, NY. Dr. Mezhebovsky, MD, Boston Clinical Trials Inc, Boston, MA. Drs. She, MD and Pathak, MD and Mr Leathers, MBA, AstraZeneca Pharmaceuticals, Wilmington, DE, USA.
authors.forename: Arifulla
authors.initials: A
authors.lastname: Khan
authors.affiliation: Dr. Khan, MD, Northwest Clinical Research Center, Bellevue, WA; Duke University School of Medicine, Department of Psychiatry and Behavioral Sciences, Durham, NC. Dr. Atkinson, MD, Finger Lakes Clinical Research, Rochester, NY. Dr. Mezhebovsky, MD, Boston Clinical Trials Inc, Boston, MA. Drs. She, MD and Pathak, MD and Mr Leathers, MBA, AstraZeneca Pharmaceuticals, Wilmington, DE, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Atkinson
authors.affiliation: Dr. Khan, MD, Northwest Clinical Research Center, Bellevue, WA; Duke University School of Medicine, Department of Psychiatry and Behavioral Sciences, Durham, NC. Dr. Atkinson, MD, Finger Lakes Clinical Research, Rochester, NY. Dr. Mezhebovsky, MD, Boston Clinical Trials Inc, Boston, MA. Drs. She, MD and Pathak, MD and Mr Leathers, MBA, AstraZeneca Pharmaceuticals, Wilmington, DE, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Mezhebovsky
authors.affiliation: Dr. Khan, MD, Northwest Clinical Research Center, Bellevue, WA; Duke University School of Medicine, Department of Psychiatry and Behavioral Sciences, Durham, NC. Dr. Atkinson, MD, Finger Lakes Clinical Research, Rochester, NY. Dr. Mezhebovsky, MD, Boston Clinical Trials Inc, Boston, MA. Drs. She, MD and Pathak, MD and Mr Leathers, MBA, AstraZeneca Pharmaceuticals, Wilmington, DE, USA.
authors.forename: Fahua
authors.initials: F
authors.lastname: She
authors.affiliation: Dr. Khan, MD, Northwest Clinical Research Center, Bellevue, WA; Duke University School of Medicine, Department of Psychiatry and Behavioral Sciences, Durham, NC. Dr. Atkinson, MD, Finger Lakes Clinical Research, Rochester, NY. Dr. Mezhebovsky, MD, Boston Clinical Trials Inc, Boston, MA. Drs. She, MD and Pathak, MD and Mr Leathers, MBA, AstraZeneca Pharmaceuticals, Wilmington, DE, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Leathers
authors.affiliation: Dr. Khan, MD, Northwest Clinical Research Center, Bellevue, WA; Duke University School of Medicine, Department of Psychiatry and Behavioral Sciences, Durham, NC. Dr. Atkinson, MD, Finger Lakes Clinical Research, Rochester, NY. Dr. Mezhebovsky, MD, Boston Clinical Trials Inc, Boston, MA. Drs. She, MD and Pathak, MD and Mr Leathers, MBA, AstraZeneca Pharmaceuticals, Wilmington, DE, USA.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Pathak
keywords: Clinical trial; Phase III; antipsychotics; anxiety disorders; sustained-release preparations; treatment efficacy