Simon Viktoria, van Winkel Ruud, De Hert Marc
Department of Psychiatry and Psychotherapy, Semmelweis University Budapest, Hungary.
J Clin Psychiatry. 2009 Jul;70(7):1041-50. doi: 10.4088/jcp.08r04392.
Numerous publications have provided evidence for clinically important metabolic adverse effects of antipsychotics, but there is no systematic evaluation as to whether weight gain and other metabolic changes are dose dependent.
This review of the available literature aimed to explore a possible relationship between dosage of second-generation antipsychotics (SGAs) and the degree of metabolic side effects.
A literature review was conducted in 3 steps: (1) Articles published between 1975 and 2004 were identified on the basis of the bibliography of an extensive review of the metabolic effects of SGAs. (2) Articles published between 2004 and 2008 were identified by a PubMed search with the keywords weight gain, metabolic, glucose, insulin, and lipid AND dose combined with amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, and ziprasidone. (3) A hand search was conducted based on the bibliography of the identified articles.
All studies that provided information on metabolic side-effects in different dose ranges were selected. Data extraction was carried out independently by 2 observers.
Preliminary evidence suggests a dose-response relationship between clozapine and olanzapine serum concentrations and metabolic outcomes, although the association between administered daily dose and metabolic outcomes is not clear. Data are controversial with regard to risperidone, and no study has as yet assessed risperidone serum concentrations in association with metabolic outcomes. For the other SGAs, there was little evidence to suggest a dose-response relationship, although, in these agents also, no assessment of serum concentrations was conducted.
The finding that metabolic complications may be associated with clozapine and olanzapine plasma concentrations provides further evidence for a causal contribution to the metabolic disturbances observed with these agents. Further well-designed, prospective studies investigating a possible association between SGA serum concentrations and metabolic outcomes are needed.
众多出版物已提供证据表明抗精神病药物存在临床上重要的代谢不良反应，但对于体重增加和其他代谢变化是否呈剂量依赖性尚无系统评估。
本对现有文献的综述旨在探讨第二代抗精神病药物（SGA）剂量与代谢副作用程度之间的可能关系。
文献综述分三步进行：（1）根据对SGA代谢效应的广泛综述的参考文献，确定1975年至2004年发表的文章。（2）通过PubMed搜索，使用关键词体重增加、代谢、葡萄糖、胰岛素、脂质以及剂量，并结合氨磺必利、阿立哌唑、氯氮平、喹硫平、利培酮、舍吲哚和齐拉西酮来确定2004年至2008年发表的文章。（3）基于已识别文章的参考文献进行手工检索。
选择所有提供不同剂量范围代谢副作用信息的研究。数据提取由两名观察者独立进行。
初步证据表明氯氮平和奥氮平血清浓度与代谢结果之间存在剂量反应关系，尽管每日给药剂量与代谢结果之间的关联尚不清楚。关于利培酮的数据存在争议，且尚无研究评估利培酮血清浓度与代谢结果的关联。对于其他SGA，几乎没有证据表明存在剂量反应关系，不过这些药物也未进行血清浓度评估。
代谢并发症可能与氯氮平和奥氮平血浆浓度相关这一发现，为这些药物所观察到的代谢紊乱的因果关系提供了进一步证据。需要进一步开展设计良好的前瞻性研究，以调查SGA血清浓度与代谢结果之间的可能关联。
