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.Electronic supplementary materialThe online version of this article (doi:10.1186/s40345-014-0014-9) contains supplementary material, which is available to authorized users.
Highlights
Bipolar disorder is a complex, debilitating illness that typically follows a chronic and recurrent course
Baseline demographics and disease characteristics were generally similar between the treatment groups (Table 1)
Secondary efficacy end points Response (≥50% reduction in Young Mania Rating Scale (YMRS) score at day 43) occurred in 79.2% and 68.2% of the lithium and placebo addon groups, respectively, and remission (YMRS total score ≤12 at day 43) was reported in 72.3% and 59.7%, respectively
Summary
Bipolar disorder is a complex, debilitating illness that typically follows a chronic and recurrent course. Manic, depressed, or mixed symptoms range in severity and rate of onset and in their most extreme forms require hospitalization (Sanchez-Moreno et al 2009). Quetiapine extended release (quetiapine XR) demonstrates efficacy as monotherapy in acute mania (Cutler et al 2011) and bipolar depression (Suppes et al 2010). Yatham et al (2004) previously reported that quetiapine immediate release (IR) added to lithium or divalproex provided superior efficacy in treating mania when compared with lithium or divalproex alone. The current study compared the efficacy and safety of lithium versus placebo as add-on to quetiapine XR in adults with bipolar I disorder with a current or recent episode of severe manic or mixed symptoms
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