Spertus Jacob, Horvitz-Lennon Marcela, Abing Haley, Normand Sharon-Lise
Department of Health Care Policy, Harvard Medical School, 180 Longwood Avenue, Boston, MA, 02115, USA.
Cambridge Health Alliance, Harvard Medical School, 1493 Cambridge Street, Cambridge, MA, 02139, USA.
NPJ Schizophr. 2018 Jun 27;4(1):12. doi: 10.1038/s41537-018-0053-9.
People with schizophrenia are at considerably higher risk of cardiometabolic morbidity than the general population. Second-generation antipsychotic drugs contribute to that risk partly through their weight gain effects, exacerbating an already high burden of disease. While standard 'as-randomized' analyses of clinical trials provide valuable information, they ignore adherence patterns across treatment arms, confounding estimates of realized treatment exposure on outcome. We assess the effect of specific second-generation antipsychotics on weight gain, defined as at least a 7% increase in weight from randomization, using a Bayesian hierarchical model network meta-analysis with individual patient level data. Our data consisted of 14 randomized clinical trials contributing 5923 subjects (mean age = 39 [SD = 12]) assessing various combinations of olanzapine (n = 533), paliperidone (n = 3482), risperidone (n = 540), and placebo (n = 1368). The median time from randomization to dropout or trial completion was 6 weeks (range: 0-60 weeks). The unadjusted probability of weight gain in the placebo group was 4.8% across trials. For each 10 g chlorpromazine equivalent dose increase in olanzapine, the odds of weight gain increased by 5 (95% credible interval: 1.4, 5.3); the effect of risperidone (odds ratio = 1.6 [0.25, 9.1]) was estimated with considerable uncertainty but no different from paliperidone (odds ratio = 1.3 [1.2, 1.5]).
精神分裂症患者发生心脏代谢疾病的风险比普通人群高得多。第二代抗精神病药物部分通过其体重增加效应导致了这种风险，加剧了本就很高的疾病负担。虽然临床试验的标准“随机分组”分析提供了有价值的信息，但它们忽略了各治疗组的依从模式，混淆了实际治疗暴露对结果的估计。我们使用贝叶斯分层模型网络荟萃分析和个体患者水平数据，评估特定第二代抗精神病药物对体重增加的影响，体重增加定义为自随机分组后体重至少增加7%。我们的数据包括14项随机临床试验，共纳入5923名受试者（平均年龄=39岁[标准差=12岁]），评估了奥氮平（n=533）、帕利哌酮（n=3482）、利培酮（n=540）和安慰剂（n=1368）的各种组合。从随机分组到退出试验或试验完成的中位时间为6周（范围：0-60周）。在各试验中，安慰剂组体重增加的未调整概率为4.8%。奥氮平每增加10克氯丙嗪等效剂量，体重增加的几率增加5倍（95%可信区间：1.4，5.3）；利培酮的效应（比值比=1.6[0.25，9.1]）估计存在较大不确定性，但与帕利哌酮无差异（比值比=1.3[1.2，1.5]）。
