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Metabolic Effects of 7 Antipsychotics on Patients With Schizophrenia: A Short-Term, Randomized, Open-Label, Multicenter, Pharmacologic Trial.
Zhang, Y, Wang, Q, Reynolds, GP, Yue, W, Deng, W, Yan, H, Tan, L, Wang, C, Yang, G, Lu, T, et al
The Journal of clinical psychiatry. 2020;(3)
Abstract
OBJECTIVE To compare longitudinal metabolic effects of 7 antipsychotics, including body mass index (BMI), waist circumference (WC), blood pressure (BP), glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C); to investigate risk factors for metabolic syndrome (MetS); and to make recommendations on frequency and timing of monitoring metabolic measurements. METHODS This randomized, open-label, pharmacologic trial was conducted among patients with schizophrenia (DSM-IV) in 32 hospitals across China. Patients were randomly assigned to 7 groups and assessed at baseline, 2, 4, and 6 weeks. Linear mixed-effect models were used to assess changes of metabolic measures over time. Multivariable logistic regression analysis was performed to investigate the risk factors for MetS. RESULTS In total, 2,550 (718 drug-naïve) of 2,774 patients finished the study between July 6, 2010, and November 30, 2011. We found significant (P < .05) changes for BMI, WC, TG, and LDL-C, with TG and LDL-C reaching a plateau. Interactions between baseline metabolic condition and changes over time were observed for BMI (χ² = 43.11, P < .001), WC (χ² = 36.34, P < .001), systolic BP (χ² = 11.92, P = .002), glucose (χ² = 6.09, P = .01), and TG (χ² = 6.01, P = .01). Antipsychotics generally had greater adverse effects on patients who were initially screened as metabolically normal. After controlling for other associated factors, we found that antipsychotics resulted in differing risk for incident MetS, with a similar pattern to findings in other populations: olanzapine (odds ratio [OR] = 3.36, P < .001) > quetiapine (OR = 3.29, P < .001) > perphenazine (OR = 2.73, P = .007) > risperidone (OR = 2.21, P = .02) > aripiprazole (OR = 1.74, P = .15) ≈ haloperidol (OR = 1.75, P = .22) ≈ ziprasidone (OR = 1, reference). CONCLUSIONS Metabolic traits should be monitored frequently in early stages of antipsychotic treatment due to rapid and substantial changes. Clinicians should not assume low risk for patients with normal metabolic parameters at baseline. TRIAL REGISTRATION Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000934.
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Genetic variants in FTO associated with metabolic syndrome: a meta- and gene-based analysis.
Wang, H, Dong, S, Xu, H, Qian, J, Yang, J
Molecular biology reports. 2012;(5):5691-8
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Abstract
The objective of this study was to examine the effect of genetic variants in fat mass and obesity associated (FTO) gene on metabolic syndrome (MetS). A systematic literature search was performed and random-effects meta-analysis was used to evaluate genetic variants in FTO with MetS. A gene-based analysis was conducted to investigate the cumulative effects of genetic polymorphisms in FTO. A total of 18 studies from 13 published papers were included in our analysis. Random-effects meta-analysis yielded an estimated odds ratio of 1.19 (95% CI 1.12-1.27; P = 1.38 × 10(-7)) for rs9939609, 1.19 (95% CI 1.05-1.35; P = 0.008) for rs8050136, and 1.89 (95% CI 1.20-2.96; P = 0.006) for rs1421085. The gene-based analysis indicated that FTO is strongly associated with MetS (P < 10(-5)). This association remains after excluding rs9939609, a SNP that was frequently reported to have strong association with obesity and MetS. In this study, we concluded that the FTO gene may play a critical role in leading to MetS. Targeting this gene may provide novel therapeutic strategies for the prevention and treatment of metabolic syndrome.