From the *Section of Psychiatry, Department of Neurosciences, University of Messina, Messina; and †Istituto Clinico "Prof. Dr. R. De Blasi," Reggio Calabria; and ‡Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy.
J Clin Psychopharmacol. 2014 Feb;34(1):129-33. doi: 10.1097/JCP.0000000000000042.
The present 16-week double-blind, randomized, placebo-controlled trial was aimed to explore the efficacy of ziprasidone add-on pharmacotherapy on clinical symptoms and cognitive functioning in 40 schizophrenic patients (active group, n = 20; placebo group, n = 20) with residual symptoms (Brief Psychiatric Rating Scale mean [SD] baseline total score in active group vs placebo, 40.4 [5.9] vs 37.9 [6.8]) despite receiving clozapine monotherapy at the highest tolerated dosage. The results obtained evidenced that ziprasidone augmentation of clozapine significantly reduced Positive and Negative Syndrome Scale "Negative" (P = 0.006, mean change [SD] in active group vs placebo, -2.7 [2.3] vs 1.1 [2.1], Cohen d = 1.7) and "General Psychopathology" (P = 0.009, mean change [SD] in active group vs placebo, -5.3 [3.8] vs -0.7 [2.0], Cohen d = 1.5). Regarding cognitive domains, ziprasidone was more effective than placebo in improving semantic fluency (P < 0.0001, mean change [SD] in active group vs placebo, 4.4 [3.5] vs -0.1 [4.1], Cohen d = 1.2). Ziprasidone had only a small effect on prolongation of heart-rate corrected QT interval (QTc) of the electrocardiogram, not significantly different from placebo (QTc milliseconds, mean [SD], week 16 in active group vs placebo, 408.17 [20.85] vs 405.45 [17.11], P = 0.321); within-group comparison revealed that QTc prolongation induced by ziprasidone was statistically significant (baseline vs week 16, P = 0.002). Ziprasidone added to clozapine was effective on negative and cognitive symptoms, although it may be proposed as a helpful treatment in schizophrenia, mainly for those patients who partially respond to clozapine monotherapy.
本 16 周双盲、随机、安慰剂对照试验旨在探讨在接受氯氮平最高耐受剂量单药治疗后仍有残留症状的 40 例精神分裂症患者（活性组，n=20；安慰剂组，n=20）中，佐匹克隆附加药物治疗对临床症状和认知功能的疗效。结果表明，佐匹克隆联合氯氮平治疗可显著降低阳性和阴性综合征量表“阴性”（P=0.006，活性组与安慰剂组的平均变化[SD]，-2.7[2.3]与 1.1[2.1]，Cohen d=1.7）和“一般精神病学”（P=0.009，活性组与安慰剂组的平均变化[SD]，-5.3[3.8]与-0.7[2.0]，Cohen d=1.5）。关于认知领域，与安慰剂相比，佐匹克隆在改善语义流畅性方面更有效（P<0.0001，活性组与安慰剂组的平均变化[SD]，4.4[3.5]与-0.1[4.1]，Cohen d=1.2）。与安慰剂相比，佐匹克隆对心电图校正 QT 间期（QTc）的延长仅有轻微影响，差异无统计学意义（QTc 毫秒，平均值[SD]，活性组第 16 周与安慰剂组，408.17[20.85]与 405.45[17.11]，P=0.321）；组内比较显示，佐匹克隆引起的 QTc 延长具有统计学意义（基线与第 16 周，P=0.002）。佐匹克隆联合氯氮平对阴性和认知症状有效，尽管它可能被提议作为精神分裂症的一种有效治疗方法，主要适用于对氯氮平单药治疗部分反应的患者。
