Simpson G M, Lindenmayer J P
Department of Psychiatry and Behavioral Sciences, University of Southern California School of Medicine, LAC/USC Medical Center 90033-1071, USA.
J Clin Psychopharmacol. 1997 Jun;17(3):194-201. doi: 10.1097/00004714-199706000-00010.
Data on extrapyramidal symptoms (EPS) from both arms of the North American multicenter comparative study of risperidone, placebo, and haloperidol were analyzed. The subjects were 523 patients with chronic schizophrenia who, after a 1-week washout period, received placebo, risperidone (2, 6, 10, or 16 mg/day), or haloperidol (20 mg/day) for 8 weeks; the trial was completed by 253 patients. Severity of EPS was assessed by means of the Extrapyramidal Symptom Rating Scale (ESRS). Mean changes (increases) in ESRS scores from baseline to worst score were significantly lower in each risperidone group than the haloperidol group on the total ESRS (parkinsonism + dystonia + dyskinesia), total parkinsonism, hypokinetic symptoms, and on the questionnaire (p < 0.001). On several of the subscales (dyskinesia, buccolinguomasticatory, and Clinical Global Impression severity of dyskinesia), mean change scores were significantly lower in some of the risperidone groups than in the placebo group (p < 0.05). At the clinically most effective risperidone dose (6 mg/day), the mean ESRS change score was not significantly different from that of the placebo group. A significant linear relationship was noted between mean change scores and increasing risperidone dose on 4 of the 12 ESRS subscales; nevertheless, even at 16 mg/day of risperidone, mean change scores were lower than in the haloperidol group. A linear relationship between increasing risperidone dose and use of antiparkinsonian medications was also apparent. Acute dystonic reactions occurred both in patients receiving risperidone and haloperidol. Patients with severe baseline EPS were at higher risk of EPS during the study than patients with low or moderate baseline EPS. It is concluded that low doses of risperidone cause few or no EPS and recommendations for initiation of risperidone treatment are made.
对北美多中心进行的利培酮、安慰剂和氟哌啶醇比较研究双臂中有关锥体外系症状（EPS）的数据进行了分析。受试者为523例慢性精神分裂症患者，经过1周的洗脱期后，接受安慰剂、利培酮（2、6、10或16毫克/天）或氟哌啶醇（20毫克/天）治疗8周；253例患者完成了试验。采用锥体外系症状评定量表（ESRS）评估EPS的严重程度。在ESRS总分（帕金森症+肌张力障碍+运动障碍）、帕金森症总分、运动减少症状以及问卷方面，从基线到最差评分时ESRS评分的平均变化（增加）在各利培酮组均显著低于氟哌啶醇组（p<0.001）。在几个分量表（运动障碍、颊舌咀嚼运动和运动障碍的临床总体印象严重程度）上，部分利培酮组的平均变化评分显著低于安慰剂组（p<0.05）。在临床最有效的利培酮剂量（6毫克/天）时，ESRS平均变化评分与安慰剂组无显著差异。在12个ESRS分量表中的4个上，平均变化评分与利培酮剂量增加之间存在显著的线性关系；然而，即使在利培酮剂量为16毫克/天时，平均变化评分仍低于氟哌啶醇组。利培酮剂量增加与抗帕金森药物使用之间也存在线性关系。接受利培酮和氟哌啶醇治疗的患者均出现了急性肌张力障碍反应。研究期间，基线EPS严重的患者比基线EPS低或中度的患者发生EPS的风险更高。得出的结论是，低剂量利培酮引起的EPS很少或没有，并给出了利培酮治疗起始的建议。
