Raben Alex T, Marshe Victoria S, Chintoh Araba, Gorbovskaya Ilona, Müller Daniel J, Hahn Margaret K
Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Front Neurosci. 2018 Jan 22;11:741. doi: 10.3389/fnins.2017.00741. eCollection 2017.
Antipsychotic-induced weight gain (AIWG) and other adverse metabolic effects represent serious side effects faced by many patients with psychosis that can lead to numerous comorbidities and which reduce the lifespan. While the pathophysiology of AIWG remains poorly understood, numerous studies have reported a positive association between AIWG and the therapeutic benefit of antipsychotic medications. To review the literature to (1) determine if AIWG is consistently associated with therapeutic benefit and (2) investigate which variables may mediate such an association. MEDLINE, Google Scholar, Cochrane Database and PsycINFO databases were searched for articles containing all the following exploded MESH terms: schizophrenia [AND] antipsychotic agents/neuroleptics [AND] (weight gain [OR] lipids [OR] insulin [OR] leptin) [AND] treatment outcome. Results were limited to full-text, English journal articles. Our literature search uncovered 31 independent studies which investigated an AIWG-therapeutic benefit association with a total of 6063 enrolled individuals diagnosed with schizophrenia or another serious mental illness receiving antipsychotic medications. Twenty-two studies found a positive association while, 10 studies found no association and one study reported a negative association. Study variables including medication compliance, sex, ethnicity, or prior antipsychotic exposure did not appear to consistently affect the AIWG-therapeutic benefit relationship. In contrast, there was some evidence that controlling for baseline BMI/psychopathology, duration of treatment and specific agent studied [i.e., olanzapine (OLZ) or clozapine (CLZ)] strengthened the relationship between AIWG and therapeutic benefit. There were limitations of the reviewed studies in that many had small sample sizes, and/or were retrospective. The heterogeneity of the studies also made comparisons difficult and publication bias was not controlled for. An AIWG-therapeutic benefit association may exist and is most likely to be observed in OLZ and CLZ-treated patients. The clinical meaningfulness of this association remains unclear and weight gain and other metabolic comorbidities should be identified and treated to the same targets as the general population. Further research should continue to explore the links between therapeutic benefit and metabolic health with emphasis on both pre-clinical work and well-designed prospective clinical trials examining metabolic parameters associated, but also occurring independently to AIWG.
抗精神病药物所致体重增加（AIWG）及其他不良代谢影响是许多精神病患者面临的严重副作用，可导致多种合并症并缩短寿命。尽管AIWG的病理生理学仍知之甚少，但众多研究报告了AIWG与抗精神病药物治疗效果之间存在正相关。为回顾文献以（1）确定AIWG是否始终与治疗效果相关，以及（2）研究哪些变量可能介导这种关联。检索了MEDLINE、谷歌学术、Cochrane数据库和PsycINFO数据库，查找包含以下所有扩展医学主题词的文章：精神分裂症[AND]抗精神病药/神经阻滞剂[AND]（体重增加[OR]脂质[OR]胰岛素[OR]瘦素）[AND]治疗结果。结果仅限于全文英文期刊文章。我们的文献检索发现了31项独立研究，这些研究调查了AIWG与治疗效果的关联，共有6063名被诊断为精神分裂症或其他严重精神疾病且正在接受抗精神病药物治疗的个体参与。22项研究发现存在正相关，10项研究未发现关联，1项研究报告为负相关。包括药物依从性、性别、种族或既往抗精神病药物暴露等研究变量似乎并未始终影响AIWG与治疗效果的关系。相比之下，有证据表明，控制基线体重指数/精神病理学、治疗持续时间以及所研究的特定药物[即奥氮平（OLZ）或氯氮平（CLZ）]可加强AIWG与治疗效果之间的关系。所回顾的研究存在局限性，许多研究样本量小，和/或为回顾性研究。研究的异质性也使得比较困难，且未控制发表偏倚。AIWG与治疗效果之间可能存在关联，最有可能在接受OLZ和CLZ治疗的患者中观察到。这种关联的临床意义仍不明确，体重增加及其他代谢合并症应与普通人群一样，针对相同目标进行识别和治疗。未来的研究应继续探索治疗效果与代谢健康之间的联系，重点关注临床前研究以及精心设计的前瞻性临床试验，这些试验既要检查与AIWG相关但也独立发生的代谢参数。
