Kelly Anne C, Sheitman Brian B, Hamer Robert M, Rhyne David C, Reed Robin M, Graham Karen A, Rau Shane W, Gilmore John H, Perkins Diana O, Peebles Susan Saik, VanderZwaag Carol J, Jarskog Lars Fredrik
From the *Department of Psychiatry, and †North Carolina Psychiatric Research Center, University of North Carolina at Chapel Hill, Chapel Hill; and ‡North Carolina Division of State Operated Healthcare Facilities, Raleigh, NC.
J Clin Psychopharmacol. 2014 Aug;34(4):441-5. doi: 10.1097/JCP.0000000000000159.
Clozapine, an evidence-based treatment of refractory schizophrenia, is associated with increased weight gain and metabolic dysregulation compared with most antipsychotics in short-term clinical trials. However, there are limited data describing comparative long-term metabolic risks. In this report, we examined whether short-term differences persist with long-term exposure to clozapine.
The data of all patients in a university-based clinic with a psychotic illness or a mood disorder with psychotic features, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis, and treated with an antipsychotic in calendar year 2012 were examined. A total of 307 patients met the criteria; 96 patients were treated with clozapine and the remaining 211 patients were treated with 1 or more non-clozapine antipsychotics. Body mass index, type 2 diabetes, hypertension, dyslipidemia, and obesity were compared.
The mean duration of the clozapine treatment was 7.6 years (range, 2 months to 21 y). On all metabolic measures, there were no statistically significant differences between the clozapine and non-clozapine groups (mean body mass index, 31 vs 32; type 2 diabetes, 17% vs 18%; dyslipidemia, 35% vs 38%; hypertension, 32% vs 39%; and obesity, 48% vs 54%). Removing the olanzapine-treated patients (n = 51) from the non-clozapine group did not change the findings.
In this university-based clinic sample with a large number of clozapine-treated patients, we found no evidence of increased risk in any individual measure for those receiving clozapine. Although speculative, the relative contribution of the increased short-term metabolic risk associated with clozapine may be diminished over time because multiple other variables likely also impact metabolic risk during the life span. Although speculative, the relative contribution of the increased short-term metabolic risk associated with clozapine may be diminished over time due to the accumulated impact of other variables that also impact metabolic risk across the life span.
氯氮平是难治性精神分裂症的循证治疗药物，在短期临床试验中，与大多数抗精神病药物相比，它与体重增加和代谢失调风险增加有关。然而，描述比较长期代谢风险的数据有限。在本报告中，我们研究了长期使用氯氮平后短期差异是否依然存在。
研究了一所大学诊所中所有在2012年日历年根据《精神障碍诊断与统计手册》第四版修订版诊断患有精神疾病或伴有精神病性特征的心境障碍且接受抗精神病药物治疗的患者数据。共有307名患者符合标准；96名患者接受氯氮平治疗，其余211名患者接受1种或多种非氯氮平抗精神病药物治疗。比较了体重指数、2型糖尿病、高血压、血脂异常和肥胖情况。
氯氮平治疗的平均时长为7.6年（范围为2个月至21年）。在所有代谢指标方面，氯氮平组和非氯氮平组之间无统计学显著差异（平均体重指数分别为31和32；2型糖尿病分别为17%和18%；血脂异常分别为35%和38%；高血压分别为32%和39%；肥胖分别为48%和54%）。从非氯氮平组中剔除接受奥氮平治疗的患者（n = 51）后，结果未改变。
在这个有大量接受氯氮平治疗患者的大学诊所样本中，我们未发现接受氯氮平治疗者在任何单项指标上风险增加的证据。尽管具有推测性，但与氯氮平相关的短期代谢风险增加的相对作用可能会随着时间推移而减弱，因为在整个生命过程中可能还有多种其他变量也会影响代谢风险。尽管具有推测性，但与氯氮平相关的短期代谢风险增加的相对作用可能会随着时间推移因其他也在整个生命过程中影响代谢风险的变量的累积作用而减弱。
