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 microg/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 < or = 12; (ii) YMRS score < or = 12 plus a Montgomery-Asberg Depression Rating Scale (MADRS) score < or = 10; (iii) YMRS score < or = 12+MADRS score < or = 8; (iv) YMRS score < or = 8; and (v) YMRS score < or = 8 plus a score < or = 2 for the YMRS core items of Irritability, Speech, Content, and Disruptive/Aggressive Behavior.
Results: In the pooled analysis, Day 21 remission rates (YMRS < or = 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 < or = 12+MADRS < or = 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 < or = 12+MADRS < or = 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 < or = 8 (31.9% versus 24.3%; p=NS). A trend in favor of quetiapine was also observed for the more stringent criterion of YMRS < or = 8 plus core items < or = 2 (28.1% versus 23.2%; p=NS). For the 6-week study, at Day 42, YMRS was < or = 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 < or = 8 were 36.5% and 32.3% (p=NS), and with YMRS < or = 8 and core items < or = 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 < or = 12+MADRS < or = 10 (63.5% versus 49.0%, p<0.05) or YMRS < or = 12+MADRS < or = 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.