Background: Metabolic syndrome in patients with schizophrenia is a major health concern. The efficacy and safety of adjunctive rosuvastatin in treating dyslipidemia were controversial.
Aims: To assess the efficacy and safety of adjunctive rosuvastatin for dyslipidemia in patients with schizophrenia.
Methods: We systematically searched for relevant controlled clinical trials from the following databases: PubMed, PsycINFO, Cochrane Library, China Knowledge Network, WanFang Database and Chinese Biomedical Database up to September 28, 2017. Standardized mean difference (SMD) and risk ratio (RR) along with their 95% confidence intervals (CIs) were calculated. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system recommendation grading method was used as the reference standard.
Results: Four studies (n=274) comparing rosuvastatin (n=138) and control (n=136) groups were identified and analyzed. Adjunctive rosuvastatin showed greater efficacy than control group in low density lipoprotein cholesterol (LDL-C) [4 trials, n=272, SMD: -1.31 (95%CI: -1.93, -0.70), I2=81%], total cholesterol (2 trials, n=164, SMD: -2.00 (95%CI: -2.79, -1.21); I2=76%) and triglycerides (2 trials, n=164, SMD: -1.05 (95%CI: -1.38, -0.72); I2=0%), but not in high density lipoprotein cholesterol (2 trials, n=164, SMD: 0.14 (95%CI: -0.16, 0.45); I2=0%). After removing one study without randomization for LDL-C, significance remained [3 trials, n=172, SMD:-1.07 (95%CI: -1.60, -0.53); I2=63%]. No significant group differences regarding body weight (3 trials, n=208, SMD: -0.40 (95%CI:-1.29, 0.49); I2=89%), body mass index (2 trials, n=164, SMD: -0.34 (95%CI: -1.23, 0.56); I2=87%), waist circumference (3 trials, n=208, SMD): -0.43 (95%CI: -1.31, 0.46); I2=89%), and fasting glucose (4 trials, n=272, SMD: -0.25 (95%CI: -0.65, 0.15); I2=62%) were observed. The adverse reactions and any cause discontinuation rate were similar between the groups. According to the GRADE approach, the evidence levels of main outcomes were rated as "very low" (35.3%) to "low" (64.7%). Of them, the primary outcome (LDL-C) was rated as "very low ".
Conclusions: The data available on the effectiveness and safety of adjunctive rosuvastatin in treating dyslipidemia for patients with schizophrenia is insufficient to come to a definitive interpretation about its efficacy and safety. Further high quality RCTs with extended treatment duration are warranted to confirm the findings.
Review registration: PROSPERO: CRD42017078230.
背景: 精神分裂症患者的代谢综合征是一个重要的健 康问题。瑞舒伐他汀对血脂异常的辅助性治疗的有效 性和安全性存在争议。.
目的: 评价瑞舒伐他汀对精神分裂症患者血脂异常的辅助性治疗的有效性和安全性。.
方法: 我们从以下数据库中系统地检索了2017 年9 月 28 日以前相关的临床对照试验：PubMed、PsycINFO、 Cochrane 图书馆、中国知网、万方数据库、中国生物 医学文献数据库。我们计算了标准平均差（SMD）、风险比（RR）及其95% 的可信区间（CIs）。使用偏移评估工具中的Cochrane 风险评估来评价所纳入研究的质量。并采用GRADE 系统推荐的等级方法（推荐、评估、发展、评价的等级）作为参照标准。.
结果: 确认和分析了4 项比较瑞舒伐他汀组（n=138）和对照组（n = 136）的研究（n = 274）。瑞舒伐他汀辅助治疗显示对低密度脂蛋白胆固醇（LDL-C） [ 4项试验，n = 272，SMD：-1.31（95%CI：-1.93，- 0.70），I2 = 81% ]、总胆固醇（2 项试验，n = 164，SMD：-2.00（95%CI：-2.79，- 1.21）；I2 = 76%）、和甘油三酯（2项试验，n = 164，SMD：-1.05（95%CI：-1.38，- 0.72）；I2 = 0%）的疗效比对照组更有效，但对高密度脂蛋白胆固醇（2 项试验，n = 164，SMD：0.14（95%CI：-0.16，0.45）；I2 = 0%）的疗效没有显著差异。去除一项没有随机试验的LDL-C 研究之后，显著差异仍然存在 [ 3 项试验，n = 172，SMD：-1.07（95%CI：-1.60，-0.53）；I2 = 63% ]。体重（3 项试验，n = 208，SMD：-0.40（95%CI：-1.29，0.49）；I2 = 89%）、身体质量指数（2 项试验，n = 164，SMD：-0.34（95%CI：-1.23，0.56）；I2 = 87%）、腰围（3 项试验，n = 208，SMD：-0.43（95%CI：-1.31，0.46）；I2 = 89%）、空腹血糖（4 项试验，n = 272，SMD：-0.25（95%CI：-0.65，0.15）；I2 = 62%）方面组间没有显著的差异。两组之间的不良反应及停药率相近。根据GRADE 分级方法，主要结果的证据水平低被评为“ 非常低”（35.3%） 到“ 低”（64.7%）。其中，主要结果（LDL-C）被评为“非常低”。.
结论: 对精神分裂症患者血脂异常的瑞舒伐他汀辅助性治疗的现有数据尚不足以对其有效性和安全性做出明确的解释。需进一步针对高质量的延长治疗时间的随机对照试验来验证该结论。.
Keywords: dyslipidemia; low density lipoprotein cholesterol; meta-analysis; rosuvastatin; schizophrenia.