A multicenter, randomized, double-blind, placebo-controlled, 16-week study of adjunctive aripiprazole for schizophrenia or schizoaffective disorder inadequately treated with quetiapine or risperidone monotherapy.
OBJECTIVE
Combining antipsychotics is common practice in the treatment of schizophrenia. This study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and schizoaffective disorder.


METHODS
In this multicenter, double-blind, 16-week, placebo-controlled study conducted at 43 American sites from July 2006 to October 2007, patients with chronic, stable schizophrenia or schizoaffective disorder diagnosed with DSM-IV-TR were randomly assigned to receive aripiprazole (2-15 mg/d) or placebo in addition to a stable regimen of quetiapine (400-800 mg/d) or risperidone (4-8 mg/d). The primary outcome measure was the mean change from baseline to endpoint (week 16, last observation carried forward) in the Positive and Negative Syndrome Scale (PANSS) total score.


RESULTS
323 subjects being treated with either risperidone (n = 177) or quetiapine (n = 146) were randomly assigned to receive adjunctive aripiprazole (n = 168) or placebo (n = 155). Baseline characteristics were similar (mean PANSS total score: aripiprazole, 74.5; placebo, 75.9) except for history of suicide attempts (aripiprazole, 27%; placebo, 40%). Nearly 70% of subjects in each arm completed the trial. Adjunctive aripiprazole and placebo groups were similar in the mean change from baseline to endpoint in the PANSS total score (aripiprazole, -8.8; placebo, -8.9; P = .942). The incidence of treatment-emergent adverse events was similar between groups. Mean changes in Simpson-Angus Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Rating Scale scores were not statistically significantly different. Adjunctive aripiprazole was associated with statistically significantly greater decreases in mean serum prolactin levels from baseline than was adjunctive placebo (-12.6 ng/mL for aripiprazole vs -2.2 ng/mL for placebo; P < .001), an effect that was seen in the risperidone subgroup (-18.7 ng/mL vs -1.9 ng/mL; P < .001) but not in the quetiapine subgroup (-3.01 ng/mL vs +0.15 ng/mL; P = .104).


CONCLUSIONS
The addition of aripiprazole to risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was generally safe and well tolerated. Further research is warranted to explore whether antipsychotic combination therapy offers benefits to particular patient populations-for example, in cases of hyperprolactinemia.


BACKGROUND
clinicaltrials.gov Identifier: NCT00325689.
Kane
John M
JM
Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY 11004-1150, USA. psychiatry@lij.edu
Correll
Christoph U
CU
Goff
Donald C
DC
Kirkpatrick
Brian
B
Marder
Stephen R
SR
Vester-Blokland
Estelle
E
Sun
Wei
W
Carson
William H
WH
Pikalov
Andrei
A
Assunção-Talbott
Sheila
S
D000328:Adult; D000553:Ambulatory Care; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D039721:Diagnostic and Statistical Manual of Mental Disorders; D003987:Dibenzothiazepines / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy*; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012720:Severity of Illness Index; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D010919:Placebos; D015363:Quinolones; D000069348:Quetiapine Fumarate; D000068180:Aripiprazole; D018967:Risperidone