G Sachs: Consultant for Abbott Laboratories, Janssen Pharmaceutica, Novartis, Eli Lilly and Company, Bristol-Myers Squibb, Glaxo SmithKline Pharmaceuticals, Elan, Sanofi, Sigma-Tau, AstraZeneca Pharmaceuticals; Grant Support from Abbott Laboratories, Janssen Pharmaceutica; Honoraria from Abbott Laboratories, Glaxo SmithKline Pharmaceuticals, Janssen Pharmaceutica, Eli Lilly and Company, Bristol-Myers Squibb, Solvay, Novartis, Sanofi, AstraZeneca Pharmaceuticals, Pfizer Inc; Stockholder – none. KNR Chengappa: has received grant/research support from Ortho McNeil and Janssen Pharmaceutica, and serves on the speakers bureau for AstraZeneca, Eli Lilly, Janssen, and Ortho McNeil. T Suppes: Sources of funding for clinical grants – Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Glaxo SmithKline Pharmaceuticals, Janssen Pharmaceutica, National Institute of Mental Health, Novartis, Robert Wood Johnson Pharmaceutical Research Institute, The Stanley Medical Research Institute; Consulting agreements/advisory boards – AstraZeneca, Bristol-Myers Squibb, Eli Lilly Research Laboratories, Glaxo SmithKline Pharmaceuticals, Janssen Pharmaceutica, Johnson & Johnson Pharmaceutical Research & Development, Pfizer, Pharmaceutical Research Institute (PRI), Ortho McNeil Pharmaceutical, UCB Pharma, Novartis Pharmaceuticals; Financial interests/stock ownership – none. JA Mullen, M Brecher, NA Devine, DE Sweitzer are all employees of AstraZeneca Pharmaceuticals.
Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study
Version of Record online: 29 APR 2004
Volume 6, Issue 3, pages 213–223, June 2004
How to Cite
Sachs, G., Chengappa, K., Suppes, T., Mullen, J., Brecher, M., Devine, N. and Sweitzer, D. (2004), Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study. Bipolar Disorders, 6: 213–223. doi: 10.1111/j.1399-5618.2004.00115.x
- Issue online: 29 APR 2004
- Version of Record online: 29 APR 2004
- Received 4 September 2003, revised and accepted for publication 19 February 2004
- bipolar disorder;
- combination therapy;
Objective: Evaluate the efficacy and tolerability of quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) in the treatment of acute mania.
Methods: Patients were randomized to 21 days of double-blind treatment with QTP plus Li/DVP, or placebo (PBO) plus Li/DVP. QTP was rapidly dosed up to a maximum of 800 mg/day; Li was dosed to 0.7–1.0 mEq/L; or DVP to 50–100 μg/mL.
Results: Fifty-six of 91 (61.5%) individuals in the QTP + Li/DVP group compared with 49 of 100 (49%) taking PBO + Li/DVP completed the study. A significantly greater mean reduction in total Young Mania Rating Scale (YMRS) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group (−13.76 versus −9.93; p = 0.021). The response rate (≥50% YMRS improvement) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients (54.3% versus 32.6%; p = 0.005), as was the proportion of patients achieving clinical remission (YMRS < 12) (45.7% versus 25.8%; p = 0.007). Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores (−1.38 versus −0.78; p = 0.001). The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria. Common adverse events (at least 10% and twice the rate of Li/DVP) in the QTP + Li/DVP group included somnolence, dry mouth, asthenia, and postural hypotension.
Conclusions: Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania. Combination therapy was well-tolerated and most adverse events were mild, withdrawal because of adverse events being only 5% compared with 6% on Li or DVP monotherapy.