Chengappa K N, Pollock B G, Parepally H, Levine J, Kirshner M A, Brar J S, Zoretich R A
Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pennsylvania 15213-2593, USA.
J Clin Psychopharmacol. 2000 Jun;20(3):311-6. doi: 10.1097/00004714-200006000-00004.
This study evaluated anticholinergic effects among patients with schizophrenia, schizoaffective disorder, or bipolar I disorder who were receiving either olanzapine (N = 12) or clozapine (N = 12) at standard clinical doses in a naturalistic setting. Serum anticholinergic levels were determined in adult male and female subjects using a radioreceptor binding assay. The Udvalg for Kliniske Undersogelser Scale was used to evaluate anticholinergic side effects clinically, and the Mini-Mental State Examination provided a global cognitive measure. Patients had achieved target doses that were stable at the time at which blood samples were obtained, and no other concomitant medicine with known anticholinergic potential was allowed. Patients receiving olanzapine (average dose, 15 mg/day) had serum anticholinergic levels of 0.96 (+/-0.55) pmol/ atropine equivalents compared with levels of 5.47 (+/-3.33) pmol/atropine equivalents for those receiving clozapine (average dose, 444 mg/day) (p < 0.001). Rates of increased and decreased salivation were significantly more common among the clozapine- and olanzapine-treated patients, respectively, whereas constipation, urinary disturbances, and tachycardia/palpitations were significantly more common among clozapine-treated patients. Neither group showed any global cognitive deficits. Olanzapine-treated patients had serum anticholinergic levels that were less than one fifth those of the clozapine-treated patients. Furthermore, clinical evaluations confirmed that clozapine-treated patients experienced more frequent and severe anticholinergic side effects (except dry mouth). However, none of the patients in either group expressed any desire to discontinue these medications as a result of the anticholinergic side effects.
本研究评估了在自然环境中接受标准临床剂量奥氮平（N = 12）或氯氮平（N = 12）治疗的精神分裂症、分裂情感性障碍或双相I型障碍患者的抗胆碱能效应。采用放射受体结合分析法测定成年男性和女性受试者的血清抗胆碱能水平。使用临床研究评定量表来临床评估抗胆碱能副作用，简易精神状态检查表提供整体认知测量。患者已达到在采集血样时稳定的目标剂量，且不允许使用其他具有已知抗胆碱能潜力的伴随药物。接受奥氮平（平均剂量，15毫克/天）的患者血清抗胆碱能水平为0.96（±0.55）皮摩尔/阿托品当量，而接受氯氮平（平均剂量，444毫克/天）的患者血清抗胆碱能水平为5.47（±3.33）皮摩尔/阿托品当量（p < 0.001）。流涎增加和减少的发生率在氯氮平和奥氮平治疗的患者中分别显著更常见，而便秘、泌尿障碍和心动过速/心悸在氯氮平治疗的患者中显著更常见。两组均未显示出任何整体认知缺陷。奥氮平治疗的患者血清抗胆碱能水平不到氯氮平治疗患者的五分之一。此外，临床评估证实氯氮平治疗的患者经历了更频繁和严重的抗胆碱能副作用（口干除外）。然而，两组患者均未因抗胆碱能副作用而表示有任何停用这些药物的意愿。
