Research Department, East London NHS Foundation Trust, London, UK.
East London NHS Foundation Trust, Newham Centre for Mental Health, Glen Road, London, E13 8SP, UK.
Clin Drug Investig. 2019 Mar;39(3):253-273. doi: 10.1007/s40261-019-00751-2.
BACKGROUND AND OBJECTIVE: Individuals with severe mental illness experience increased morbidity and mortality as a result of metabolic problems that may partly be related to the adverse effects of antipsychotics. Compared with first-generation antipsychotics, second-generation antipsychotics collectively are considered to have stronger associations with lipid abnormalities, but evidence for this specific claim has not been systematically reviewed. The objective of this review was to evaluate the risk of dyslipidaemia with second-generation versus first-generation antipsychotics amongst individuals with severe mental illness.
Major electronic databases were searched until November 2018. Studies were eligible if they were cross-sectional, cohort, case-control or interventional, where any individual second-generation antipsychotic was directly compared with first-generation antipsychotics in individuals with severe mental illness, and where lipid metabolism was a primary or secondary outcome. The evidence was reviewed and appraised according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
In total, 18 studies were eligible. The reported associations between second-generation antipsychotics vs. first-generation antipsychotics with dyslipidaemia were inconsistent, with high variability between studies and only a full qualitative synthesis was feasible. We had sufficient data, however, to undertake limited meta-analyses for clozapine, olanzapine and risperidone, all showing mildly elevated associations with dyslipidaemia "caseness" (clozapine, odds ratio 1.26, 95% confidence interval 1.16-1.38; olanzapine, odds ratio 1.29, 95% confidence interval 0.89-1.87; risperidone, odds ratio 1.05, 95% confidence interval 0.80-1.37) compared with first-generation antipsychotics, but heterogeneity was high (all I > 50%, p < 0.05). Clozapine was also associated with increased triglycerides (standardised mean difference = 0.51, 95% confidence interval 0.21-0.81, I = 5.74%), but not with cholesterol. Compared with haloperidol, neither olanzapine nor risperidone was associated with statistically significant increases in cholesterol or triglycerides.
There was considerable variation in study design and methodologies. Determining the comparative risk of second-generation vs. first-generation antipsychotics as a group of antipsychotics for lipid dysregulation may be of limited clinical utility, as drugs from either group have the potential to cause such adversity to varying degrees. It is therefore more valuable to consider the metabolic risks of specific antipsychotics rather than focusing on collective metabolic effects belonging to either antipsychotic group.
严重精神疾病患者由于代谢问题而导致发病率和死亡率增加，这些代谢问题部分可能与抗精神病药物的不良反应有关。与第一代抗精神病药相比，第二代抗精神病药通常与脂质异常的相关性更强，但尚未系统地评估这一具体说法的证据。本研究旨在评估严重精神疾病患者使用第二代抗精神病药与第一代抗精神病药相比发生血脂异常的风险。
主要电子数据库检索至 2018 年 11 月。如果研究为横断面研究、队列研究、病例对照研究或干预性研究，并且在严重精神疾病患者中任何一种第二代抗精神病药都与第一代抗精神病药直接比较，并且脂质代谢为主要或次要结局，则认为该研究符合条件。根据系统评价和荟萃分析的首选报告项目（PRISMA）指南对证据进行审查和评估。
共有 18 项研究符合条件。第二代抗精神病药与第一代抗精神病药相比与血脂异常的关联不一致，研究之间存在高度变异性，仅可行定性综合分析。然而，我们有足够的数据对氯氮平、奥氮平和利培酮进行有限的荟萃分析，结果均显示与血脂异常“病例”有轻度升高的关联（氯氮平，比值比 1.26，95%置信区间 1.16-1.38；奥氮平，比值比 1.29，95%置信区间 0.89-1.87；利培酮，比值比 1.05，95%置信区间 0.80-1.37），但异质性很高（均 I > 50%，p < 0.05）。氯氮平还与甘油三酯升高相关（标准化均数差=0.51，95%置信区间 0.21-0.81，I=5.74%），但与胆固醇无关。与氟哌啶醇相比，奥氮平和利培酮均与胆固醇或甘油三酯的统计学显著升高无关。
研究设计和方法存在较大差异。确定第二代抗精神病药与第一代抗精神病药作为一组抗精神病药治疗脂质失调的相对风险可能具有有限的临床意义，因为来自任何一组的药物都有可能在不同程度上引起这种不良反应。因此，考虑特定抗精神病药的代谢风险比关注属于任何一组抗精神病药的集体代谢效应更有价值。
