Kane John M, Correll Christoph U, Goff Donald C, Kirkpatrick Brian, Marder Stephen R, Vester-Blokland Estelle, Sun Wei, Carson William H, Pikalov Andrei, Assunção-Talbott Sheila
Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY 11004-1150, USA.
J Clin Psychiatry. 2009 Oct;70(10):1348-57. doi: 10.4088/JCP.09m05154yel.
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.
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.
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).
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.
clinicaltrials.gov Identifier: NCT00325689.
联合使用抗精神病药物是治疗精神分裂症的常见做法。本研究调查了阿立哌唑辅助利培酮或喹硫平治疗精神分裂症和分裂情感性障碍的疗效。
在2006年7月至2007年10月于美国43个地点进行的这项多中心、双盲、为期16周的安慰剂对照研究中，符合《精神疾病诊断与统计手册》第四版修订版（DSM-IV-TR）诊断标准的慢性、稳定型精神分裂症或分裂情感性障碍患者，在稳定服用喹硫平（400 - 800 mg/天）或利培酮（4 - 8 mg/天）的基础上，被随机分配接受阿立哌唑（2 - 15 mg/天）或安慰剂治疗。主要疗效指标是阳性与阴性症状量表（PANSS）总分从基线到终点（第16周，末次观察值结转）的平均变化。
323例正在接受利培酮（n = 177）或喹硫平（n = 146）治疗的受试者被随机分配接受阿立哌唑辅助治疗（n = 168）或安慰剂治疗（n = 155）。除自杀未遂史外（阿立哌唑组为27%，安慰剂组为40%），两组基线特征相似（PANSS总分均值：阿立哌唑组为74.5，安慰剂组为75.9）。每组近70%的受试者完成了试验。阿立哌唑辅助治疗组和安慰剂组在PANSS总分从基线到终点的平均变化方面相似（阿立哌唑组为 - 8.8，安慰剂组为 - 8.9；P = 0.942）。两组治疗中出现的不良事件发生率相似。Simpson - Angus量表、异常不自主运动量表和Barnes静坐不能评定量表得分的平均变化在统计学上无显著差异。与安慰剂辅助治疗相比，阿立哌唑辅助治疗使血清催乳素水平从基线的平均下降幅度在统计学上显著更大（阿立哌唑组为 - 12.6 ng/mL，安慰剂组为 - 2.2 ng/mL；P < 0.001），这种效应在利培酮亚组中可见（- 18.7 ng/mL vs - 1.9 ng/mL；P < 0.
