Abstract
SummaryBackgroundAntipsychotic treatment is associated with metabolic disturbance. However, the degree to which metabolic alterations occur in treatment with different antipsychotics is unclear. Predictors of metabolic dysregulation are poorly understood and the association between metabolic change and change in psychopathology is uncertain. We aimed to compare and rank antipsychotics on the basis of their metabolic side-effects, identify physiological and demographic predictors of antipsychotic-induced metabolic dysregulation, and investigate the relationship between change in psychotic symptoms and change in metabolic parameters with antipsychotic treatment.MethodsWe searched MEDLINE, EMBASE, and PsycINFO from inception until June 30, 2019. We included blinded, randomised controlled trials comparing 18 antipsychotics and placebo in acute treatment of schizophrenia. We did frequentist random-effects network meta-analyses to investigate treatment-induced changes in body weight, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, and glucose concentrations. We did meta-regressions to examine relationships between metabolic change and age, sex, ethnicity, baseline weight, and baseline metabolic parameter level. We examined the association between metabolic change and psychopathology change by estimating the correlation between symptom severity change and metabolic parameter change.FindingsOf 6532 citations, we included 100 randomised controlled trials, including 25 952 patients. Median treatment duration was 6 weeks (IQR 6–8). Mean differences for weight gain compared with placebo ranged from −0·23 kg (95% CI −0·83 to 0·36) for haloperidol to 3·01 kg (1·78 to 4·24) for clozapine; for BMI from −0·25 kg/m2 (−0·68 to 0·17) for haloperidol to 1·07 kg/m2 (0·90 to 1·25) for olanzapine; for total-cholesterol from −0·09 mmol/L (−0·24 to 0·07) for cariprazine to 0·56 mmol/L (0·26–0·86) for clozapine; for LDL cholesterol from −0·13 mmol/L (−0.21 to −0·05) for cariprazine to 0·20 mmol/L (0·14 to 0·26) for olanzapine; for HDL cholesterol from 0·05 mmol/L (0·00 to 0·10) for brexpiprazole to −0·10 mmol/L (−0·33 to 0·14) for amisulpride; for triglycerides from −0·01 mmol/L (−0·10 to 0·08) for brexpiprazole to 0·98 mmol/L (0·48 to 1·49) for clozapine; for glucose from −0·29 mmol/L (−0·55 to −0·03) for lurasidone to 1·05 mmol/L (0·41 to 1·70) for clozapine. Greater increases in glucose were predicted by higher baseline weight (p=0·0015) and male sex (p=0·0082). Non-white ethnicity was associated with greater increases in total cholesterol (p=0·040) compared with white ethnicity. Improvements in symptom severity were associated with increases in weight (r=0·36, p=0·0021), BMI (r=0·84, p<0·0001), total-cholesterol (r=0·31, p=0·047), and LDL cholesterol (r=0·42, p=0·013), and decreases in HDL cholesterol (r=–0·35, p=0·035).InterpretationMarked differences exist between antipsychotics in terms of metabolic side-effects, with olanzapine and clozapine exhibiting the worst profiles and aripiprazole, brexpiprazole, cariprazine, lurasidone, and ziprasidone the most benign profiles. Increased baseline weight, male sex, and non-white ethnicity are predictors of susceptibility to antipsychotic-induced metabolic change, and improvements in psychopathology are associated with metabolic disturbance. Treatment guidelines should be updated to reflect our findings. However, the choice of antipsychotic should be made on an individual basis, considering the clinical circumstances and preferences of patients, carers, and clinicians.FundingUK Medical Research Council, Wellcome Trust, National Institute for Health Research Oxford Health Biomedical Research Centre.
Highlights
Antipsychotics form the mainstay of treatment for patients with schizophrenia, but many, especially the secondgeneration antipsychotics, are associated with weight gain, lipid disturbance, and glucose dysregulation, thereby contributing to the development of metabolic syndrome.[1]
We identified strong evidence that antipsychotic-associated improvements in psychopathology are associated with metabolic disturbance
We found that antipsychotics vary markedly in their effects on body weight, body-mass index (BMI), total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and glucose concentrations
Summary
Antipsychotics form the mainstay of treatment for patients with schizophrenia, but many, especially the secondgeneration antipsychotics, are associated with weight gain, lipid disturbance, and glucose dysregulation, thereby contributing to the development of metabolic syndrome.[1]. Whether an association exists between antipsychotic-induced metabolic dysregulation and symptom change in patients, as suggested by some, but not all previous longitudinal studies,[7,8,9] is unclear. We did a network meta-analysis of trials comparing antipsychotics in the treatment of schizophrenia, aiming to investigate the relative effects of various drugs on body weight, body-mass index (BMI), and metabolic measures (fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides). We did bivariate meta-analyses and meta-regression analyses of placebo-controlled data to investigate whether baseline demographic and physiological factors predict the mag nitude of antipsychotic-induced metabolic change, and whether a relationship exists between metabolic change and change in severity of psychotic symptoms during antipsychotic treatment
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
