van Kammen D P, McEvoy J P, Targum S D, Kardatzke D, Sebree T B
Department of Psychiatry, University of Pittsburgh School of Medicine, PA 15206, USA.
Psychopharmacology (Berl). 1996 Mar;124(1-2):168-75. doi: 10.1007/BF02245618.
Sertindole is a novel antipsychotic agent with high selectivity for the mesolimbic dopaminergic pathway and nanomolar affinities for dopamine D2, serotonin 5-HT2, and norepinephrine NE alpha 1 receptors. This 40-day randomized, placebo-controlled, dose-ranging multicenter study was designed to assess the effect of sertindole on previously neuroleptic-responsive, hospitalized schizophrenic patients (n = 205). Sertindole doses began at 4 mg/day and were increased to 8, 12, or 20 mg/day, depending on randomization. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Extrapyramidal symptoms (EPS) were assessed by movement rating scales, EPS-related adverse events, and use of anti-EPS medications. A dose-related improvement was observed for PANSS, BPRS, and CGI, with statistically significant mean differences (P < 0.05) between placebo and 20-mg/day sertindole (decreases from baseline of -5.8 versus -16.9 for PANSS, -4.8 versus -10.4 for BPRS, respectively). The differences in CGI final improvement score between placebo and 20-mg/day sertindole were 3.8 versus 2.9, respectively. EPS-related events were comparable in the placebo and sertindole groups. In conclusion, sertindole 20 mg/day was effective, well tolerated, and not associated with significant motor system abnormalities.
舍吲哚是一种新型抗精神病药物，对中脑边缘多巴胺能通路具有高选择性，对多巴胺D2、5-羟色胺5-HT2和去甲肾上腺素NEα1受体具有纳摩尔亲和力。这项为期40天的随机、安慰剂对照、剂量范围多中心研究旨在评估舍吲哚对先前对抗精神病药物有反应的住院精神分裂症患者（n = 205）的疗效。舍吲哚剂量从4毫克/天开始，根据随机分组情况增加到8、12或20毫克/天。疗效指标包括阳性和阴性症状量表（PANSS）、简明精神病评定量表（BPRS）和临床总体印象（CGI）。锥体外系症状（EPS）通过运动评定量表、与EPS相关的不良事件以及抗EPS药物的使用来评估。观察到PANSS、BPRS和CGI有剂量相关的改善，安慰剂组和20毫克/天舍吲哚组之间存在统计学显著的平均差异（P < 0.05）（PANSS从基线下降分别为-5.8对-16.9，BPRS为-4.8对-10.4）。安慰剂组和20毫克/天舍吲哚组的CGI最终改善评分差异分别为3.8对2.9。安慰剂组和舍吲哚组的EPS相关事件相当。总之，20毫克/天的舍吲哚有效、耐受性良好，且与显著的运动系统异常无关。
