The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) as maintenance monotherapy for patients with generalized anxiety disorder (GAD). Time-to-event (anxiety symptom recurrence; maximum 52 weeks) multicenter, randomized-withdrawal, parallel-group, double-blind, placebo-controlled study of quetiapine XR (50–300 mg/day) following open-label run-in (4–8 weeks) and open-label stabilization (≥12 weeks). Primary variable: time from randomization to anxiety event. Secondary variables included: Hamilton Anxiety Rating Scale (HAM-A) total, HAM-A psychic/somatic anxiety factors, Clinical Global Impression-Severity of Illness (CGI-S), and Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scores; adverse events (AE) reporting. Four hundred and thirty-two patients, stabilized on quetiapine XR, were randomized to continue quetiapine XR (N=216) or switch to placebo (N=216). Risk of anxiety symptom recurrence was significantly reduced by 81% for quetiapine XR versus placebo: hazard ratio=0.19 (95% confidence interval 0.12–0.31; P<0.001). Fewer patients receiving quetiapine XR (N=22, 10.2%) than placebo (N=84, 38.9%) experienced anxiety symptom recurrence. Significant differences were observed between quetiapine XR and placebo in: HAM-A total, psychic/somatic, CGI-S (all P<0.001) and Q-LES-Q (P<0.05) scores. AEs (>10%) during open-label treatment were dry mouth, sedation, somnolence, dizziness, fatigue, and constipation. During randomized treatment, the most common AEs for quetiapine XR were headache and nasopharyngitis. Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR, with tolerability results consistent with the known profile of quetiapine.
aSTART Clinic for Mood and Anxiety Disorders, Toronto
bDepartment of Psychiatry, University of Toronto
cNorthern Ontario School of Medicine
dDepartment of Psychology, Lakehead University, Ontario, Canada
eMaster of Public Health Program (Lakehead University)
fDepartment of Psychiatry and Behavioral Sciences, Medical University of South Carolina and The Ralph H. Johnson VA Medical Center, Charleston, South Carolina
gNational Center for Mental Health, Mandaluyong City, Philippines
hAstraZeneca R&D, Södertälje, Sweden
iAstraZeneca Pharmaceuticals, Wilmington, Delaware, USA
Correspondence to Dr Martin A. Katzman, c/o START Clinic for the Mood and Anxiety Disorders, 32 Park Road, Toronto, Ontario, M4W 2N4, Canada Tel: +1 416 598 9344; fax: +1 416 598 8198; e-mail: email@example.com
Previous presentation of trial results: Poster presented at the 63rd Annual Society of Biological Psychiatry, Washington, DC, USA 1–3 May 2008.
Poster presented at the 161st Annual Meeting of the American Psychiatric Association, Washington, DC, USA, 3–8 May 2008.
Poster presented at the 48th Annual New Clinical Drug Evaluation Unit Meeting, Phoenix, Arizona, USA, 27–30 May 2008.
Poster presented at the XIV World Congress of Psychiatry, Prague, Czech Republic, 20–25 September 2008.
Received June 1, 2010
Accepted July 13, 2010