title: Lithium as add-on to quetiapine XR in adult patients with acute mania: a 6-week, multicenter, double-blind, randomized, placebo-controlled study.
abstract: Quetiapine extended release (XR) and lithium are treatments with proven efficacy in acute mania. This randomized study evaluated the efficacy and safety of lithium or placebo as add-on to quetiapine XR in adult patients with manic or mixed symptoms of bipolar I disorder. In this 6-week, double-blind study (Trial D144AC00003), adult patients with DSM-IV-TR-diagnosed bipolar I disorder (current episode manic or mixed), a Young Mania Rating Scale (YMRS) total score ≥20, and score ≥4 on two of four core YMRS items were administered quetiapine XR (400 to 800 mg/day) and randomly assigned to receive add-on lithium (600 to 1,800 mg/day) or placebo. The primary efficacy end point was change in the YMRS total score from baseline to day 43, analyzed using a mixed-model for repeated measures (MMRM) approach. Secondary efficacy and safety end points were also measured. Rating scales were administered by trained staff. Three hundred fifty-six patients treated with quetiapine XR were randomized to add-on lithium (n = 173) or placebo (n = 183). Two hundred ninety-one patients (81.7%) completed the study. At day 43, least squares mean change in YMRS total score was -22.8 for add-on lithium and -20.1 for add-on placebo, a statistically significant treatment group difference of -2.69 (p < 0.001). On secondary measures, add-on lithium was associated with significant improvements in response, remission, illness severity, and overall illness versus add-on placebo (p < 0.05). The number needed to treat was 9.1 for response and 7.9 for remission for add-on lithium compared with add-on placebo. Lithium in combination with quetiapine XR was generally well tolerated, with a similar profile to quetiapine XR in combination with placebo. The addition of lithium to quetiapine XR therapy was associated with significantly greater efficacy than placebo as add-on and was generally well tolerated in patients with acute bipolar I mania. This study was registered under Clinicaltrials.gov Identifier NCT00931723.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Nantes, 98, rue Joseph Blanchart, 44100 Nantes, France.
authors.forename: Michel S
authors.initials: MS
authors.lastname: Bourin
authors.affiliation: Department of Psychiatry and Psychotherapy, Technical University of Dresden, Dresden, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Severus
authors.affiliation: Cape Trial Centre, Cape Town, South Africa.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Schronen
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Gass
authors.affiliation: AstraZeneca R&D, Södertälje, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Szamosi
authors.affiliation: AstraZeneca R&D, Södertälje, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Eriksson
authors.affiliation: Bangalore Medical College and Research institute, Victoria Hospital, Bangalore, India.
authors.forename: Hongally
authors.initials: H
authors.lastname: Chandrashekar
keywords: Bipolar mania; Lithium; Quetiapine XR