Wayne State University Eugene Applebaum College of Pharmacy and Health Sciences, Department of Pharmacy Practice, 259 Mack Avenue, Suite 2190, Detroit, MI 48201, USA.
Wayne State University School of Medicine, Division of Endocrinology, 4201 St Antoine, Detroit, MI 48201, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Apr 20;83:55-63. doi: 10.1016/j.pnpbp.2018.01.004. Epub 2018 Jan 8.
Atypical antipsychotics increase the risk of diabetes and cardiovascular disease through their side effects of insulin resistance and weight gain. The populations for which atypical antipsychotics are used carry a baseline risk of metabolic dysregulation prior to medication which has made it difficult to fully understand whether atypical antipsychotics cause insulin resistance and weight gain directly. The purpose of this work was to conduct a systematic review and meta-analysis of atypical antipsychotic trials in healthy volunteers to better understand their effects on insulin sensitivity and weight gain. Furthermore, we aimed to evaluate the occurrence of insulin resistance with or without weight gain and with treatment length by using subgroup and meta-regression techniques. Overall, the meta-analysis provides evidence that atypical antipsychotics decrease insulin sensitivity (standardized mean difference=-0.437, p<0.001) and increase weight (standardized mean difference=0.591, p<0.001) in healthy volunteers. It was found that decreases in insulin sensitivity were potentially dependent on treatment length but not weight gain. Decreases in insulin sensitivity occurred in multi-dose studies <13days while weight gain occurred in studies 14days and longer (max 28days). These findings provide preliminary evidence that atypical antipsychotics cause insulin resistance and weight gain directly, independent of psychiatric disease and may be associated with length of treatment. Further, well-designed studies to assess the co-occurrence of insulin resistance and weight gain and to understand the mechanisms and sequence by which they occur are required.
非典型抗精神病药物通过其导致胰岛素抵抗和体重增加的副作用，增加了患糖尿病和心血管疾病的风险。使用非典型抗精神病药物的人群在开始用药之前就存在代谢失调的基线风险，这使得人们很难完全理解非典型抗精神病药物是否直接导致胰岛素抵抗和体重增加。这项工作的目的是对健康志愿者中的非典型抗精神病药物试验进行系统评价和荟萃分析，以更好地了解它们对胰岛素敏感性和体重增加的影响。此外，我们旨在通过亚组和荟萃回归技术评估是否存在体重增加和无体重增加的胰岛素抵抗以及与治疗时间的关系。总的来说，荟萃分析提供的证据表明，非典型抗精神病药物会降低健康志愿者的胰岛素敏感性（标准化均数差=-0.437，p<0.001）和增加体重（标准化均数差=0.591，p<0.001）。研究发现，胰岛素敏感性的降低可能与治疗时间有关，但与体重增加无关。胰岛素敏感性的降低发生在 13 天以下的多剂量研究中，而体重增加发生在 14 天及以上的研究中（最长 28 天）。这些发现初步表明，非典型抗精神病药物直接导致胰岛素抵抗和体重增加，与精神疾病无关，并且可能与治疗时间有关。此外，需要进行精心设计的研究来评估胰岛素抵抗和体重增加的同时发生情况，并了解它们发生的机制和顺序。
