A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder.
OBJECTIVE
To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder.


METHODS
In an international, multicenter, double-blind, parallel-group, 12-week study, patients with a DSM-IV diagnosis of bipolar I disorder (manic episode) were randomly assigned to treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or lithium. The primary efficacy measure was change from baseline in Young Mania Rating Scale (YMRS) score at day 21. Data were gathered from April 2001 to May 2002.


RESULTS
More patients in the quetiapine (72/107) and lithium (67/98) groups completed the study compared with the placebo group (35/97). Improvement (reduction) in YMRS score was significantly greater for quetiapine than placebo at day 7 (-8.03 vs. -4.89; p < .01), and the difference between groups continued to increase over time to day 21 (-14.6 vs. -6.7; p < .001) and to endpoint at day 84 (-20.3 vs. -9.0; p < .001). Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 (53.3% vs. 27.4%; p < .001) and at day 84 (72.0% vs. 41.1%; p < .001). Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures. Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure. The most common adverse events for quetiapine were dry mouth, somnolence, and weight gain, while lithium was associated with tremor and insomnia. The quetiapine and placebo groups had similar, low levels of extrapyramidal symptom-related adverse events.


CONCLUSIONS
Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated.
Bowden
Charles L
CL
Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. bowdenc@uthscsa.edu
Grunze
Heinz
H
Mullen
Jamie
J
Brecher
Martin
M
Paulsson
Björn
B
Jones
Martin
M
Vågerö
Mårten
M
Svensson
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006760:Hospitalization; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced; D008094:Lithium / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D012720:Severity of Illness Index; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010919:Placebos; D000069348:Quetiapine Fumarate; D008094:Lithium