Aripiprazole monotherapy in the treatment of acute bipolar I mania: a randomized, double-blind, placebo- and lithium-controlled study.
OBJECTIVE
To evaluate the efficacy and safety of aripiprazole as acute and maintenance of effect monotherapy for acute bipolar mania.


METHODS
Patients with acute bipolar I mania (DSM-IV-TR: YMRS > or =20), manic or mixed (with or without psychotic features) were randomized to double-blind aripiprazole (15-30 mg/day; n=155), placebo (n=165) or lithium (900-1500 mg/day; n=160) (1:1:1) for 3 weeks. Aripiprazole- and lithium-treated patients remained on blinded treatment for 9 additional weeks. The primary outcome was the mean change from baseline in YMRS Total score (LOCF) to Week 3. Secondary outcomes included the mean change from baseline in YMRS Total score (LOCF) at all other timepoints up to Week 12.


RESULTS
Aripiprazole demonstrated significantly greater improvement than placebo in mean YMRS Total score from baseline to Day 2 (-4.3 vs.-2.8; p=0.003), and up to Week 3 (-12.6 vs. -9.0; p<0.001). Significant improvement in YMRS Total score was also seen with lithium versus placebo at Week 3 (-12.0 vs. -9.0; p=0.005). Improvements in YMRS Total score were maintained to Week 12 for aripiprazole (-14.5) and lithium (-12.7). Response rates at Week 3 were significantly higher with aripiprazole (46.8%) and lithium (45.8%) than placebo (34.4%; both p<0.05, LOCF); increasing to Week 12 with aripiprazole (56.5%) and lithium (49.0%). Most common adverse events with aripiprazole were headache, nausea, akathisia, sedation, and constipation; with lithium were nausea, headache, constipation, and tremor.


CONCLUSIONS
Aripiprazole provided statistically significant improvement of acute mania within 2 days, continuing over 3 weeks and sustained over 12 weeks. The magnitude of improvement to Week 12 was similar with aripiprazole and lithium.
Keck
P E
PE
Psychopharmacology Research Program, Department of Psychiatry, University of Cincinnati College of Medicine, and Linder Center of HOPE, Mason, Ohio 45267, USA. paul.keck@uc.edu
Orsulak
P J
PJ
Cutler
A J
AJ
Sanchez
R
R
Torbeyns
A
A
Marcus
R N
RN
McQuade
R D
RD
Carson
W H
WH
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006261:Headache / Q000139:chemically induced; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D015430:Weight Gain
D014150:Antipsychotic Agents; D018020:Lithium Compounds; D010879:Piperazines; D010919:Placebos; D015363:Quinolones; D000068180:Aripiprazole