Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study.
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 microg/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 (> or =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.
Sachs
G
G
Harvard Bipolar Research Program, Massachusetts General Hospital, Boston, 02114, USA. sachsg@aol.com
Chengappa
K N R
KN
Suppes
T
T
Mullen
J A
JA
Brecher
M
M
Devine
N A
NA
Sweitzer
D E
DE
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D000069348:Quetiapine Fumarate; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D000927:Anticonvulsants; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D016651:Lithium Carbonate; D000069348:Quetiapine Fumarate; D014635:Valproic Acid