Rates of remission/euthymia with quetiapine in combination with lithium/divalproex for the treatment of acute mania

Abstract

Objective The aim of this analysis was to compare the rates of remission/euthymia in patients with bipolar mania receiving quetiapine in combination with lithium/divalproex (QTP + Li/DVP) versus placebo (PBO) in combination with Li/DVP (PBO + Li/DVP). Methods A pooled analysis of two (one 3-week and one 6-week) double-blind studies of a total of 370 patients hospitalized with bipolar I mania who received quetiapine (up to 800 mg/day) in combination with Li (mean serum concentration 0.76 mEq/L) or DVP (mean serum concentration 69.5 μg/mL) was performed. For both studies, data were analyzed at Day 21. In addition, for the 6-week study, data were analyzed at Day 42. Five different criteria for remission/euthymia were used: (i) Young Mania Rating Scale (YMRS) score ≤ 12; (ii) YMRS score ≤ 12 plus a Montgomery–Asberg Depression Rating Scale (MADRS) score ≤ 10; (iii) YMRS score ≤ 12 + MADRS score ≤ 8; (iv) YMRS score ≤ 8; and (v) YMRS score ≤ 8 plus a score ≤ 2 for the YMRS core items of Irritability, Speech, Content, and Disruptive/Aggressive Behavior. Results In the pooled analysis, Day 21 remission rates (YMRS ≤ 12) were significantly higher in patients treated with QTP + Li/DVP compared with those who received PBO + Li/DVP (48.7% versus 33.0%, p = 0.003). Rates of remission/euthymia (YMRS ≤ 12 +MADRS ≤ 10) were similarly improved with QTP + Li/DVP compared with Li/DVP alone (43.2% versus 26.5%, p = 0.001). Using the most stringent criteria (YMRS ≤ 12 + MADRS ≤ 8), rates of remission/euthymia were again significantly higher with QTP + Li/DVP than with Li/DVP alone (38.4% versus 25.9%, p = 0.014). More patients treated with quetiapine met the stringent criterion of YMRS ≤ 8 (31.9% versus 24.3%; p = NS). A trend in favor of quetiapine was also observed for the more stringent criterion of YMRS ≤ 8 plus core items ≤ 2 (28.1% versus 23.2%; p = NS). For the 6-week study, at Day 42, YMRS was ≤ 12 in 68.3% of patients treated with QTP + Li/DVP compared with 57.3% of those who received PBO + Li/DVP ( p = NS). Respective rates based on the remission criterion of YMRS ≤8 were 36.5% and 32.3% ( p = NS), and with YMRS ≤ 8 and core items ≤ 2 were 53.8% and 45.8% ( p = NS). However, a significant difference was observed between patients treated with QTP + Li/DVP versus those treated with PBO + Li/DVP using criteria of YMRS ≤12 + MADRS ≤ 10 (63.5% versus 49.0%, p < 0.05) or YMRS ≤ 12 +MADRS ≤ 8 (61.5% versus 46.9%, p < 0.05). Conclusions At Days 21 and 42, quetiapine combined with Li/DVP compared to Li/DVP monotherapy yielded significant, sustained improvements in the rate of clinical remission/euthymia in patients with bipolar mania. Longer-term studies are warranted to assess whether quetiapine combined with other mood stabilizing medications can yield even longer-term resolution of symptoms of acute mania while concurrently preventing emergence of depressive symptoms.