Efficacy of adjunctive aripiprazole to either valproate or lithium in bipolar mania patients partially nonresponsive to valproate/lithium monotherapy: a placebo-controlled study.
OBJECTIVE
The authors evaluated the efficacy and safety of adjunctive aripiprazole in bipolar I patients with mania partially nonresponsive to lithium/valproate monotherapy.


METHODS
This multicenter, randomized, placebo-controlled study included outpatients experiencing a manic or mixed episode (with or without psychotic features). Patients with partial nonresponse to lithium/valproate monotherapy (defined as a Young Mania Rating Scale total score >/=16 at the end of phases 1 and 2, with a decrease of </=25% between phases) with target serum concentrations of lithium (0.6-1.0 mmol/liter) or valproate (50-125 mug/ml) were randomly assigned in a 2:1 ratio to adjunctive aripiprazole (N=253; 15 or 30 mg/day) or placebo (N=131) for 6 weeks.


RESULTS
Mean improvement from baseline in Young Mania Rating Scale total score at week 6 (primary endpoint) was significantly greater with aripiprazole (-13.3) than with placebo (-10.7). Significant improvements in Young Mania Rating Scale total score with aripiprazole versus placebo occurred from week 1 onward. In addition, the mean improvement in Clinical Global Impression Bipolar Version (CGI-BP) severity of illness (mania) score from baseline to week 6 was significantly greater with aripiprazole (-1.9) than with placebo (-1.6). Discontinuation rates due to adverse events were higher with aripiprazole than with placebo (9% versus 5%, respectively). Akathisia was the most frequently reported extrapyramidal symptom-related adverse event and occurred significantly more frequently among those receiving aripiprazole (18.6%) than among those receiving placebo (5.4%). There were no significant differences between treatments in weight change from baseline to week 6 (+0.55 kg and +0.23 kg for aripiprazole and placebo, respectively; last observation carried forward).


CONCLUSIONS
Adjunctive aripiprazole therapy showed significant improvements in mania symptoms as early as week 1 and demonstrated a tolerability profile similar to that of monotherapy studies.
Vieta
Eduard
E
Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, Villarroel 170/Rossello 140, 08036 Barcelona, Spain. evieta@clinic.ub.es
T'joen
Caroline
C
McQuade
Robert D
RD
Carson
William H
WH
Marcus
Ronald N
RN
Sanchez
Raymond
R
Owen
Randall
R
Nameche
Laurence
L
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D000927:Anticonvulsants; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D018020:Lithium Compounds; D010879:Piperazines; D015363:Quinolones; D014635:Valproic Acid; D000068180:Aripiprazole