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Metabolic Effects of 7 Antipsychotics on Patients With Schizophrenia: A Short-Term, Randomized, Open-Label, Multicenter, Pharmacologic Trial.
J Clin Psychiatry. 2020 03 24; 81(3)JC

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.

Authors+Show Affiliations

Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Biomolecular Science Research Centre, Sheffield Hallam University, Sheffield, United Kingdom.Peking University Sixth Hospital (Institute of Mental Health), Beijing, China. National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Peking University Sixth Hospital (Institute of Mental Health), Beijing, China. National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China.Second Xiangya Hospital, Central South University, Hunan, China.Beijing Anding Hospital, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.Beijing HuiLongGuan Hospital, Beijing, China.Peking University Sixth Hospital (Institute of Mental Health), Beijing, China. National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China.Peking University Sixth Hospital (Institute of Mental Health), Beijing, China. National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China.Wuxi Mental Health Center, Nanjing Medical University, Wuxi, Jiangshu, China.Institute of Mental Health, Tianjin Anding Hospital, Tianjin, China. Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China.Hebei Mental Health Center, Baoding, Hebei, China.Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China.Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Peking University Sixth Hospital (Institute of Mental Health), Beijing, China. National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China.Beijing Anding Hospital, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.Beijing HuiLongGuan Hospital, Beijing, China.Second Xiangya Hospital, Central South University, Hunan, China.Beijing Tiantan Hospital, Capital Medical University, Beijing, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.No affiliation info availableMental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Huaxi Biobank, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.Peking University Sixth Hospital (Institute of Mental Health), Beijing, China. National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China.#28 Dianxin South St, Chengdu 610041, Sichuan, China. litaohx@scu.edu.cn. Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32237292

Citation

Zhang, Yamin, et al. "Metabolic Effects of 7 Antipsychotics On Patients With Schizophrenia: a Short-Term, Randomized, Open-Label, Multicenter, Pharmacologic Trial." The Journal of Clinical Psychiatry, vol. 81, no. 3, 2020.
Zhang Y, Wang Q, Reynolds GP, et al. Metabolic Effects of 7 Antipsychotics on Patients With Schizophrenia: A Short-Term, Randomized, Open-Label, Multicenter, Pharmacologic Trial. J Clin Psychiatry. 2020;81(3).
Zhang, Y., Wang, Q., Reynolds, G. P., Yue, W., Deng, W., Yan, H., Tan, L., Wang, C., Yang, G., Lu, T., Wang, L., Zhang, F., Yang, J., Li, K., Lv, L., Tan, Q., Li, Y., Yu, H., Zhang, H., ... Li, T. (2020). Metabolic Effects of 7 Antipsychotics on Patients With Schizophrenia: A Short-Term, Randomized, Open-Label, Multicenter, Pharmacologic Trial. The Journal of Clinical Psychiatry, 81(3). https://doi.org/10.4088/JCP.19m12785
Zhang Y, et al. Metabolic Effects of 7 Antipsychotics On Patients With Schizophrenia: a Short-Term, Randomized, Open-Label, Multicenter, Pharmacologic Trial. J Clin Psychiatry. 2020 03 24;81(3) PubMed PMID: 32237292.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolic Effects of 7 Antipsychotics on Patients With Schizophrenia: A Short-Term, Randomized, Open-Label, Multicenter, Pharmacologic Trial. AU - Zhang,Yamin, AU - Wang,Qiang, AU - Reynolds,Gavin P, AU - Yue,Weihua, AU - Deng,Wei, AU - Yan,Hao, AU - Tan,Liwen, AU - Wang,Chuanyue, AU - Yang,Guigang, AU - Lu,Tianlan, AU - Wang,Lifang, AU - Zhang,Fuquan, AU - Yang,Jianli, AU - Li,Keqing, AU - Lv,Luxian, AU - Tan,Qingrong, AU - Li,Yinfei, AU - Yu,Hua, AU - Zhang,Hongyan, AU - Ma,Xin, AU - Yang,Fude, AU - Li,Lingjiang, AU - Chen,Qi, AU - Wei,Wei, AU - Zhao,Liansheng, AU - Wang,Huiyao, AU - Li,Xiaojing, AU - Guo,Wanjun, AU - Hu,Xun, AU - Tian,Yang, AU - Ren,Hongyan, AU - Ma,Xiaohong, AU - Coid,Jeremy, AU - Zhang,Dai, AU - Li,Tao, AU - ,, Y1 - 2020/03/24/ PY - 2019/02/12/received PY - 2019/10/16/accepted PY - 2020/4/3/entrez PY - 2020/4/3/pubmed PY - 2020/9/15/medline JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 81 IS - 3 N2 - 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. SN - 1555-2101 UR - https://www.unboundmedicine.com/medline/citation/32237292/Metabolic_Effects_of_7_Antipsychotics_on_Patients_With_Schizophrenia:_A_Short_Term_Randomized_Open_Label_Multicenter_Pharmacologic_Trial_ L2 - http://www.psychiatrist.com/JCP/article/Pages/rapid-metabolic-changes-after-antipsychotic-treatment.aspx DB - PRIME DP - Unbound Medicine ER -