A double blind, randomized, placebo-controlled trial of quetiapine as an add-on therapy to lithium or divalproex for the treatment of bipolar mania
ABSTRACT The aim of this study was to evaluate the efficacy and tolerability of quetiapine combined with lithium or divalproex in the treatment of bipolar mania. Patients were randomized to 6 weeks of quetiapine (up to 800 mg/day) and lithium/divalproex (Li/DVP) (target trough serum concentrations of 0.7-1.0 mEq/L and 50-100 microg/mL, respectively) or placebo and lithium/divalproex. Quetiapine+lithium/divalproex treatment (n=104) showed a 2.0-point greater improvement on the primary outcome (change from baseline in Young Mania Rating Scale total score at day 21) compared with placebo+lithium/divalproex (n=96), and a 2.8-point greater difference by day 42, but the differences between groups were not statistically significant. Other efficacy measures, however, did show a statistically significant advantage in favor of quetiapine+lithium/divalproex over lithium/divalproex monotherapy at day 42. Improvement of mean Young Mania Rating Scale scores with quetiapine+lithium/divalproex was numerically but not statistically significantly greater than lithium/divalproex monotherapy in the treatment of bipolar mania. Potential reasons for the failure of quetiapine+lithium/divalproex to differentiate from placebo+lithium/divalproex treatment on the primary outcome measure and the implications of this for the treatment of mania and future studies are discussed. Overall, the combination of quetiapine with lithium or divalproex was well tolerated.
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ABSTRACT: The use of combination therapy with mood stabilizers and antipsychotics in acute mania in bipolar disorder (BD) is widespread, although most treatment guidelines recommend monotherapy as the first option, and reserve combination therapy, which is associated with more frequent and more severe side effects, for when patients do not respond to the former treatment option. Reasons to prescribe combination therapy include the lack of efficacy of the current treatment (either real or due to undisclosed poor adherence), psychiatric comorbidities, severe previous course of illness, slow cross-tapering during treatment switching, and potential benefits from particular combinations. The decision to start with monotherapy or combination therapy may depend on the patient characteristics, and is still under debate. Clinical trials designed to ascertain whether combination therapy or monotherapy is more advantageous for patients in acute mania and beyond, according to illness severity, are urgently needed. Adding a third monotherapy arm to the conventional two-arm, adjunctive-design trials or initiating combination therapy from the beginning may help to shed some light on the issue.CNS Drugs 02/2015; 29(3). DOI:10.1007/s40263-015-0235-1 · 4.38 Impact Factor
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ABSTRACT: Pharmacotherapy remains the mainstay of treatment for acute bipolar mania, but there are many choices, including mood stabilizers (MSs) and antipsychotics (APs).CNS Drugs 08/2014; 28(11). DOI:10.1007/s40263-014-0197-8 · 4.38 Impact Factor
American Journal of Health-System Pharmacy 01/2008; 65(2):115-116. DOI:10.2146/ajhp070564 · 2.21 Impact Factor