Baymiller Scott P, Ball Patricia, McMahon Robert P, Buchanan Robert W
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, P.O. Box 21247, Baltimore, MD 21228, USA.
Schizophr Res. 2003 Jan 1;59(1):49-57. doi: 10.1016/s0920-9964(02)00158-5.
We examined the effects of long-term clozapine treatment, concurrent treatment with beta-adrenergic antagonists, and clozapine-induced weight gain on serum glucose and lipid measures. Fifty subjects met the DSM-III-R criteria for schizophrenia or schizoaffective disorder, participated in a 10-week, double-blind comparison of haloperidol and clozapine and a 1-year, open-label clozapine trial, and had available serum glucose and lipid levels. Weight and glucose, and lipid laboratory values were measured at the baseline and throughout the double-blind and year-long study. There were significant increases in serum triglyceride, total cholesterol, and glucose levels during the course of clozapine treatment. There were no significant changes in high-density lipoprotein (HDL) or low-density lipoprotein (LDL). Propranolol and atenolol had additive effects on changes in the total cholesterol and triglycerides, with propranolol having the most pronounced effects. Propranolol and atenolol had no significant effect on the serum glucose levels. There were significant correlations between the triglyceride and HDL level changes and clozapine-associated weight gain during the study. There were no significant correlations between the change in serum total cholesterol, LDL, or glucose and weight gain. Clozapine therapy has adverse effects on glucose and lipid homeostasis, with clozapine-induced changes in serum glucose likely due to the inherent pharmacological properties of clozapine. Concurrent beta-adrenergic receptor antagonist treatment may have an additive effect on serum lipids, and clozapine-associated weight gain also plays a modest role in triglyceride increases.
我们研究了长期使用氯氮平治疗、与β-肾上腺素能拮抗剂联合治疗以及氯氮平引起的体重增加对血清葡萄糖和脂质指标的影响。50名符合精神分裂症或分裂情感性障碍的DSM-III-R标准的受试者，参与了一项为期10周的氟哌啶醇与氯氮平双盲比较试验以及一项为期1年的氯氮平开放标签试验，且有可用的血清葡萄糖和脂质水平数据。在基线以及整个双盲和为期一年的研究过程中测量了体重、葡萄糖和脂质实验室值。在氯氮平治疗过程中，血清甘油三酯、总胆固醇和葡萄糖水平显著升高。高密度脂蛋白（HDL）或低密度脂蛋白（LDL）无显著变化。普萘洛尔和阿替洛尔对总胆固醇和甘油三酯的变化有相加作用，其中普萘洛尔的作用最为明显。普萘洛尔和阿替洛尔对血清葡萄糖水平无显著影响。在研究期间，甘油三酯和HDL水平变化与氯氮平相关的体重增加之间存在显著相关性。血清总胆固醇、LDL或葡萄糖的变化与体重增加之间无显著相关性。氯氮平治疗对葡萄糖和脂质稳态有不良影响，氯氮平引起的血清葡萄糖变化可能归因于氯氮平固有的药理特性。同时使用β-肾上腺素能受体拮抗剂治疗可能对血清脂质有相加作用，且氯氮平相关的体重增加在甘油三酯升高方面也起一定作用。
