Risk factors and pattern of weight gain in youths using antipsychotic drugs (original) (raw)
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Pediatric Drugs, 2013
Objectives The aims of this study were to provide a systematic review and meta-analysis of the effects of atypical antipsychotics in children and adolescents on weight gain (primary objective) and other metabolic parameters (secondary objective). Methods A systematic literature review and meta-analysis of double-blind, randomized, controlled trials were conducted. The data sources used were as follows: EMBASE, PubMed, BIOSIS, International Pharmaceutical Abstracts, The Cochrane database (Clinical Trials), Clinical Trials Government Registry, The metaRegister of Controlled Trials, WHO (World Health Organization) Clinical Trials Registry Platform, and PsycINFO Ò . Hand searching was also carried out by examining the reference lists of identified studies. Double-blind, randomized, controlled trials investigating the metabolic adverse effects (weight gain, lipid, glucose, and prolactin level abnormalities) associated with atypical antipsychotic use in children and adolescents aged B18 years were included, irrespective of whether the investigation of adverse effects was a primary or secondary endpoint. Results We identified 21 studies of drug versus placebo that met the inclusion criteria, with a total of 2,455 patients, 14 studies for risperidone (1,331 patients), three for olanzapine (276 patients), and four for aripiprazole (848 patients). Compared with placebo, the mean weight increases for each drug were olanzapine 3.45 kg (95 % CI 2.93-3.98), risperidone 1.77 kg (95 % CI 1.35-2.20), and aripiprazole 0.94 kg (95 % CI 0.65-1.24). Regarding other metabolic abnormalities, eight studies reported statistically significant increases in prolactin with risperidone; two reported a statistically significant increase in glucose, total cholesterol, and prolactin with olanzapine; and three studies reported a statistically significant decrease in prolactin with aripiprazole. Data on lipid, glucose, and prolactin level changes were too limited to allow us to perform a meta-analysis. Conclusions Olanzapine, risperidone, and aripiprazole were all associated with statistically significant weight gain. Olanzapine was associated with the most weight gain and aripiprazole the least. For the secondary outcome, although a number of active comparator trials were identified, data were not available for meta-analysis and were too limited to allow firm conclusions to be drawn.
Weight gain associated with atypical antipsychotic drugs: mechanisms and management
Expert Review of Neurotherapeutics, 2003
disorders. Although their profile of potent antagonism at specific serotonin and dopamine receptors offers certain advantages compared with typical antipsychotics, their use has been associated with various adverse effects, including significant weight gain. This adverse effect is of particular concern in children and adolescents, secondary to the immediate and long-term health risks associated with weight gain, including obesity, diabetes mellitus, and hyperlipidemia. Indeed, from 1963 to 1991, the prevalence of obesity has approximately doubled in youth. Prior to selecting an atypical antipsychotic, a detailed review of the predictors of weight gain is necessary for every child and adolescent. Published data suggest that clozapine and olanzapine are associated with considerable weight gain, whereas risperidone and quetiapine have a moderate risk. Alternatively, ziprasidone and aripiprazole may exhibit a low risk for this adverse effect. Whereas behavioral and pharmacologic measures are available to manage weight gain associated with atypical antipsychotics, research is needed to establish more effective and safe interventions for this adverse effect in children and adolescents.
Weight gain associated with clozapine, olanzapine and risperidone in children and adolescents
Journal of Neural Transmission, 2007
The study was aimed at the evaluation of weight gain associated with atypical antipsychotics and its clinical risk factors in children and adolescents. Weight and body mass index (BMI) of initially hospitalised patients treated with clozapine (n ¼ 15), olanzapine (n ¼ 15), and risperidone (n ¼ 15) were prospectively monitored on a weekly basis for the first 6 weeks. Different clinical risk factors were tested for their association with weight gain in the three groups. All three groups experienced significant weight gain between baseline and endpoint (p < 0.0001). For all weight measures, planned comparisons were all significant between olanzapine vs. clozapine and risperidone, respectively. Average weight gain was significantly higher for the olanzapine group (mean ¼ 4.6 kg, SD ¼ 1.9) than for the risperidone (mean ¼ 2.8 kg, SD ¼ 1.3) and clozapine (mean ¼ 2.5 kg, SD ¼ 2.9) groups. Olanzapine and risperidone, but not clozapine, caused a disproportionately higher weight gain in children and adolescents in comparison to adults.
Journal of Child and Adolescent Psychopharmacology, 2018
Background: Antipsychotic-related weight gain is a common clinically relevant side effect when treating psychotic disorders in pediatric populations, yet few predictors and no moderators of antipsychotic-related weight gain are known. Methods: The Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) study randomized 119 youths (age 8-19 years) with schizophrenia or schizoaffective disorder to 8 weeks of antipsychotic treatment with molindone, risperidone, or olanzapine and assessed treatment response and side effects. In this secondary analysis, we used multivariable linear regression and receiver operating characteristic analysis to investigate predictors and moderators of weight change and percent weight change from baseline to week 8. Results: Treatment assignment was the most discriminant predictor of weight change [F(2, 66) = 17.00, p < 0.001] and percent weight change [F(2, 66) = 16.85, p < 0.001]. Mean weight gain was 0.74 (standard deviation-3.51) kg for molindone, 4.13-3.79 kg for risperidone, and 7.29-3.44 kg for olanzapine. After adjusting for treatment assignment, lower pretreatment hemoglobin A1C (HgbA1C) predicted more weight gain [F(1, 55) = 4.71, p = 0.03]. Diagnosis (schizoaffective vs. schizophrenia) moderated weight change [F(2, 63) = 6.02, p = 0.004] and percent weight change [F(2, 63) = 5.26, p = 0.008] such that schizoaffective diagnosis predicted larger weight gain for youths in the risperidone treatment arm. Age, sex, family income, baseline weight, and symptoms neither predicted nor moderated weight change or percent weight change. Conclusion: We identified prognostic subgroups and novel risk factors for antipsychotic-related weight gain. We confirmed that antipsychotic choice is extremely important for predicting future weight gain. We also found that younger age did not predict greater weight gain, in contrast to prior studies. Our findings require replication in an independent sample because we did not adjust for multiple comparisons to minimize false negatives. ClinicalTrials.gov Identifier: NCT00053703
Weight gain and metabolic side effects with antipsychotic drugs in children
Middle East Current Psychiatry, 2012
Background Weight gain and metabolic side effects are some of the most troublesome side effects of atypical antipsychotics, especially when used in children and adolescents. There have been few studies on these side effects in children in Arab countries. Objectives To determine weight gain and metabolic side effects in a group of children and adolescents on antipsychotic drugs (APDs) and to compare different group of atypical antipsychotics and typical APDs in terms of these side effects. Methods Sixty-four patients younger than 18 years of age with different psychiatric diagnoses and different types of APDs were assessed in terms of weight, height, BMI at the start of the study, and then after 3 and 6 months. Estimation of the BMI z-score and metabolic profile including fasting blood glucose, fasting lipid profile, and liver transaminases was carried out. Results Significant weight gain and increase in BMI were found after 6 months (mean 3.5 ± 3 and 1.7 ± 1.2, respectively). In addition, 50% of our patients were either overweight or obese and 4.7% fulfilled the criteria of metabolic syndrome and 46.9% had one to two symptoms of metabolic syndrome. Weight gain was more common at a younger age and metabolic side effects were associated significantly with obesity. Although olanzapine led to the greatest weight gain 6.1 ± 5.6 kg, there were no significant differences in weight gain and metabolic side effects between different drugs. Conclusion All groups of APD showed significant weight gain and increase in BMI; in addition, obesity was associated significantly with metabolic side effects. Therefore, prescription of APD to children should be revised and done only by professional child psychiatrists, with careful monitoring of weight and metabolic profile.
Effects of long-term antipsychotics treatment on body weight: A population-based cohort study
Journal of Psychopharmacology, 2019
Background: Antipsychotics are often prescribed for long-term periods, however, most evidence of their impact on body weight comes from short-term clinical trials. Particularly, impact associated with dosage has been barely studied. Aims: The aim of this study was to describe the short- and long-term change in body weight of people initiated on high or low doses of the three most commonly prescribed second-generation antipsychotics. Methods: Retrospective cohorts of individuals with a diagnosed psychotic disorder observed from 2005 to 2015 in the UK primary care. The exposure was the first prescription of olanzapine, quetiapine or risperidone. The main outcome was change in body weight four years before and four years after initiation of antipsychotic treatment, stratified on sex and ‘low’ or ‘high’ dose. Results: In total, 22,306 women and 16,559 men were observed. Olanzapine treatment was associated with the highest change in weight, with higher doses resulting in more weight gain...
Metabolic Effects of Antipsychotics on Adiposity and Insulin Sensitivity in Youths
JAMA Psychiatry
IMPORTANCE Antipsychotic medications are commonly used to treat nonpsychotic disruptive behavioral disorders in youths. OBJECTIVE To characterize the metabolic effects of first exposure to antipsychotics in youths using criterion standard assessments of body composition and insulin sensitivity. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial recruited antipsychotic-naive youths aged 6 to 18 years in the St Louis, Missouri, metropolitan area who were diagnosed with 1 or more psychiatric disorders and clinically significant aggression and in whom antipsychotic treatment was considered. Participants were enrolled from June 12, 2006, through November 10, 2010. Enrolled participants were randomized (1:1:1) to 1 of 3 antipsychotics commonly used in children with disruptive behavioral disorders and evaluated for 12 weeks. Data were analyzed from January 17, 2011, through August 9, 2017. INTERVENTIONS Twelve weeks of treatment with oral aripiprazole (n = 49), olanzapine (n = 46), or risperidone (n = 49). MAIN OUTCOMES AND MEASURES Primary outcomes included percentage total body fat measured by dual-energy x-ray absorptiometry (DXA) and insulin sensitivity in muscle measured via hyperinsulinemic clamps with stable isotopically labeled tracers. Secondary outcomes included abdominal adiposity measured by magnetic resonance imaging (MRI) and adipose and hepatic tissue insulin sensitivity measured via clamps with tracers. RESULTS The intention-to-treat sample included 144 participants (98 males [68.1%]; mean [SD] age, 11.3 [2.8] years); 74 (51.4%) were African American, and 43 (29.9%) were overweight or obese at baseline. For the primary outcomes, from baseline to week 12, DXA percentage total body fat increased by 1.18% for risperidone, 4.12% for olanzapine, and 1.66% for aripiprazole and was significantly greater for olanzapine than risperidone or aripiprazole (time by treatment interaction P < .001). From baseline to week 12, insulin-stimulated change in glucose rate of disappearance increased by 2.30% for risperidone and decreased by 29.34% for olanzapine and 30.26% for aripiprazole, with no significant difference across medications (time by treatment interaction, P < .07). This primary measure of insulin sensitivity decreased significantly during 12 weeks in the pooled study sample (effect of time, F = 17.38; P < .001). For the secondary outcomes from baseline to week 12, MRI measured abdominal fat increased, with subcutaneous fat increase significantly greater for olanzapine than risperdone or aripiprazole (time by treatment, P = .003). Behavioral improvements occurred with all treatments. CONCLUSIONS AND RELEVANCE Adverse changes in adiposity and insulin sensitivity were observed during 12 weeks of antipsychotic treatment in youths, with the greatest fat increases on olanzapine. Such changes, likely attributable to treatment, may be associated with risk for premature cardiometabolic morbidity and mortality. The results inform risk-benefit considerations for antipsychotic use in youths.
J Ayub Med Coll Abbottabad, 2010
Background: Studies from the Western world have shown that antipsychotic medications in psychiatric patients result in weight gain and other metabolic diseases. This study was undertaken to investigate whether any one of the five most commonly prescribed antipsychotics, (risperidone, olanzepine, trifluoperazine, quetiapine and haloperidol) could behave differently in terms of causing weight gain among patients attending the psychiatric outpatient clinics in a tertiary care hospital in Karachi, Pakistan. Methods: For this retrospective cohort study, data were collected from outpatient records of the Aga Khan University Hospital, from 2003 to 2007. Demographic and clinical data were analysed. Repeated measures ANOVA, using a linear mixed model approach was used to assess weight gain over time due to the use of antipsychotic medications. Results: A total of 124 subject records (68 males and 56 females) were evaluated. One-way ANOVA revealed that the groups being prescribed with antipsychotics were comparable with respect to age, duration of treatment and weight measurements. Frequencies were calculated which showed that weight increases significantly over time with respect to the prescribed antipsychotic medications, except for risperidone. Repeated measures ANOVA using the linear mixed model approach showed that the serial weight measurements were significantly different across the follow up times (p<0.05). Conclusion: Four of the commonly prescribed antipsychotic drugs do result in an increase in weight; however risperidone has no such effect, making it an option in treating psychiatric disorders without worrying for any gain in weight. In view of the increased prevalence of obesity and other metabolic diseases, measures should be taken towards careful prescription of antipsychotic medications.
… : Clinical and Experimental, 2010
Objective To document prospective weight and anthropometric changes in children and adolescents during the first 12 weeks of treatment with risperidone and evaluate metabolic outcomes including plasma leptin levels. Method Eight patients with psychotic disorders (ages 11-17) who had started risperidone (mean: 1.80 mg/day; sd ¼ 1.04) in the prior 4 weeks participated in this observational study. Fasting morning blood samples were obtained at baseline and week 8 to assess glucose, leptin, cortisol, insulin, and triglycerides. Measures of body mass index (BMI), weight, waist and hip circumference, blood pressure, and heart rate were obtained weekly. Results Participants increased in mean weight (4.16 kg; sd ¼ 4.36; p ¼ 0.03) and BMI (1.47 kg/m 2 ; sd ¼ 1.53; p ¼ 0.03) with five out of eight gaining at least 7% of baseline body weight. They had a 4.03 cm (sd ¼ 3.82; p ¼ 0.02) increase in waist circumference and a 5.17 cm (sd ¼ 3.68; p ¼ 0.01) increase in hip circumference. Leptin trended higher, but did not reach statistical significance. There were no significant changes in glucose, insulin, cortisol, blood pressure, or heart rate. Conclusion Subjects experienced significant increases in weight, BMI, hip and waist circumference during the first 3 months of treatment. Better powered research with more advanced anthropometric assessment is warranted to further elucidate mechanisms of antipsychotic associated weight gain in youth.
Weight gain and antipsychotics. Data from EUFEST study
Context. Schizophrenia is a chronic disease most frequently necessitating lifelong antipsychotic treatment. Selecting which antipsychotic is to be prescribed in an individual schizophrenia patient represents an important clinical decision that need to take into account efficacy and side effects. Objective. Evaluating weight gain related with one year antipsychotic treatment in antipsychotic naive firstepisode schizophrenia patients. Design. This study is an analysis of weight gain associated with typical or atypical antipsychotics used in European First Episode Schizophrenia Trial (EUFEST) study. Subjects and Methods. 113 first episode naïve antipsychotic schizophrenia patients included in EUFEST - Romanian cohort, who were randomized to one of the 5 treatment arms. Weight was obtained at baseline, 3, 6, 9 and 12 months for the 5 antipsychotics (typical-Haloperidol; atypical-Olanzapine, Amisulpride, Ziprasidone, Quetiapine). Results. There are no statistically significant differences between groups treated with typical or atypical antipsychotics or between any individual antipsychotics concerning weight gain during the study. Weight gain was the highest in the first 3 months (57.49%) for all the studied neuroleptics. At the end of the study, the less increase was observed with ziprasidone (3.87 kg) and the highest with olanzapine (9.83 kg). Conclusion. Increase in weight has taken place for each individual neuroleptic, but also as a group (all neuroleptics) in the first three months (57.49%). Therefore, we should address the issue of weight gain with great care, especially in first period of antipsychotic administration, in order to fast deploy intervention tailored to maintain pretreatment weight.