Type 2 Diabetes in Children and Adolescents on Atypical Antipsychotics

Pramyothin, Pornpoj; Khaodhiar, Lalita

doi:10.1007/s11892-015-0623-4

Cited by 15 publications

(11 citation statements)

References 66 publications

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“…Taking as an example the metabolic-related ADRs, the highest risk of weight gain in pediatric patients seems to be associated with the administration of olanzapine and clozapine followed by risperidone, quetiapine, haloperidol, aripiprazole, and ziprasidone. On the other hand, ziprasidone and clozapine are more commonly associated with the onset of cardiovascular adverse events, such as electrocardiogram (ECG) abnormalities and hypertension (17,18). As far as hyperprolactinemia is concerned, risperidone seems to induce it quite frequently, whereas aripiprazole does not seem to show any effects on prolactin (PRL) levels (14,16).…”

Section: Introductionmentioning

confidence: 99%

Safety and Tolerability of Antipsychotic Drugs in Pediatric Patients: Data From a 1-Year Naturalistic Study

Cicala

Santoro

Tata³

et al. 2020

Front. Psychiatry

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Background: Antipsychotic drugs (APs) are increasingly used to treat a variety of psychiatric disorders in children and adolescents. However, their safety and tolerability profiles, when used in a developmental age context, show different characteristics from the ones observed in adult patients. Treatment with APs in pediatric patients is often long-term. However, the tolerability data regarding these patients mostly derive from short-term studies.Methods: Starting from April 2017, for a 1-year period, patients between 4 and 18 years of age followed by five units of developmental age neuropsychiatry, who initiated a treatment with at least an AP (ATC class N05A) were included into the study. Patient-related data have been collected at baseline and regularly thereafter, as allowed by the clinical routine. Changes to continuous variables over time have been analyzed using a linear mixed model in subsamples of our population treated with risperidone or aripiprazole.Results: During the observation period, 158 patients were initially enrolled, but only 116 completed 12 months of therapy with an AP. Risperidone was the most used AP (n = 52) followed by aripiprazole (n = 44) and olanzapine (n = 7). For both the aripiprazole and risperidone groups, the mean body mass index (BMI) (P < 0.001 for both groups) and heart rate (P = 0.026 for aripiprazole group and P < 0.001 for the risperidone one) values significantly increased over time. The mean prolactin concentration value significantly increased over time only in the risperidone group (P = 0.04). Eighty-six patients experienced at least one adverse drug reaction (ADR), accounting for a total of 238 specific reactions, with the most frequent being weight gain (n = 34), increased serum prolactin levels (n = 21), hyperphagia (n = 20), and hypercholesterolemia (n = 14). Among these, only 24 ADRs were classifiable as serious.Cicala et al. Antipsychotic Drugs in Pediatric PatientsConclusions: The results of this study confirm that risperidone and aripiprazole are relatively well-tolerated therapeutic options for the treatment of a variety of psychiatric disorders in pediatric patients. However, in findings such as statistically significant increments of BMI and heart rate mean values, the variations over time in prolactin levels observed with risperidone and the differences between the two drugs remark the necessity of systematic monitoring.

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Section: Introductionmentioning

confidence: 99%

Safety and Tolerability of Antipsychotic Drugs in Pediatric Patients: Data From a 1-Year Naturalistic Study

Cicala

Santoro

Tata³

et al. 2020

Front. Psychiatry

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“…Figure 1 further showed that the cumulative risk of developing type 2 DM increased gradually with the longer follow-up period among patients with ASD, indicating that the long-term clinical course of ASD may play an important role in the development of type 2 DM. Moreover, several studies have reported the increased prevalence of atypical antipsychotics use in the ASD population in these decades (16)(17)(18)(19)(20) and revealed the association between the use of atypical antipsychotics and type 2 DM in the adolescent and young adult populations (21)(22)(23)(24). In our study, compared with the control group and after adjustment for demographic data, use of atypical antipsychotics, and medical Furthermore, increasing evidence suggests the potential association between maternal metabolic disorders (obesity and type 2 DM) and childhood ASD (25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Risk of Developing Type 2 Diabetes in Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Study

et al. 2016

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OBJECTIVEStudies have suggested the association between autism spectrum disorder (ASD) and type 2 diabetes mellitus (DM)-related risk factors, such as obesity and dyslipidemia. However, the association between ASD and type 2 DM remains unknown. RESEARCH DESIGN AND METHODSWe used the Taiwan National Health Insurance Research Database for enrolling 6,122 adolescents and young adults with ASD and 24,488 age-and sex-matched control subjects between 2002 and 2009 and monitored them until the end of 2011. Participants who developed type 2 DM during the follow-up period were identified. RESULTS Adolescents (hazard ratio CONCLUSIONSAdolescents and young adults with ASD were more likely to develop type 2 DM during the follow-up. In addition, those with ASD using atypical antipsychotics exhibited a high risk. Therefore, further research is necessary to investigate the common pathophysiology of ASD and type 2 DM.Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social cognition, interaction, and communication as well as by repetitive behavior and restricted interests (1-3). Population reports have revealed a consistent and significant rise in ASD prevalence worldwide of ;0.6-0.7%; the latest large-scale studies have estimated a 1-2% increase (1-3). Males are 2 to 3 times more likely to be affected by ASD than are females, indicating the crucial role of sex-linked factors at the genetic, endocrine, epigenetic, and environmental levels in the pathophysiology of ASD (1-3). However, the precise etiology of ASD remains unclear.

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“…A few studies also demonstrate improvement in metabolic parameters such as fasting glucose, but have not directly examined treatment of established diabetes associated with atypical antipsychotics. Some of the studies include lifestyle modification alone and in combination with metformin and they demonstrate additive effects of lifestyle and of metformin on weight management . However, maintaining lifestyle modification is particularly challenging in patients on antipsychotic medications.…”

Section: Common Medications That Decrease Both Insulin Sensitivity Anmentioning

confidence: 99%

“…Some of the studies include lifestyle modification alone and in combination with metformin and they demonstrate additive effects of lifestyle and of metformin on weight management. 21,26,27 However, maintaining lifestyle modification is particularly challenging in patients on antipsychotic medications. The consensus expert opinion is to approach atypical antipsychoticassociated diabetes as for type 2 diabetes.…”

Section: Atypical Antipsychotic Medicationsmentioning

confidence: 99%

Medication‐induced diabetes mellitus

Repaske

2016

Pediatr Diabetes

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Epidemiological studies and case reports have demonstrated an increased rate of development of diabetes mellitus consequent to taking diverse types of medication. This review explores this evidence linking these medications and development of diabetes and presents postulated mechanisms by which the medications might cause diabetes. Some medications are associated with a reduction in insulin production, some with reduction in insulin sensitivity, and some appear to be associated with both reduction in insulin production and insulin sensitivity. Patients are often taking multiple medications and so it is hard to determine which medication was responsible for the side effect. For example, organ transplant patients may be taking a glucocorticoid and a calcineurin inhibitor, so an epidemiological study has difficulty ascribing the side effect to one or the other or the combination of these medications. There are also covariants such as the weight gain associated with steroids or antipsychotics making it difficult to know if development of diabetes was a primary or secondary effect of the medication. When we turn to deciphering the mechanism by which a medication caused diabetes, there are often multiple plausible molecular mechanisms identified in animal or in vitro studies, but these do not necessarily identify the clinically relevant mechanism(s) in humans. Finally, for pediatrics, there are few studies in children and data from adults can only be assumed to apply to children.A summary of the most common medications that have been associated with development of diabetes and their most plausible mechanism is presented in Table 1. | COMMON MEDICATIONS THAT DECREASE BOTH INSULIN SENSITIVITY AND INSULIN RELEASE | GlucocorticoidsGlucocorticoids are widely used medications and clinical experience indicates that diabetes is a frequent side effect. Ingle first reported glucosuria in rats receiving glucocorticoid.1 A human retrospective epidemiological study of adult Medicaid patients carried out over 9 years identified almost 12 000 persons with new onset diabetes and closely matched controls which did not develop diabetes.Patients who were taking glucocorticoid were more likely to be in the diabetes group (relative risk 2.23) and the relative risk was dose dependent. 2 One intuitive hypothesis for the mechanism by which glucocorticoids cause diabetes is development of insulin resistance.To test this hypothesis, hyperinsulinemic-euglycemic clamps with tritiated glucose tracer were performed on 10 healthy subjects ). In addition, there is evidence for decreased insulininduced vasodilation in muscle leading to reduced glucose delivery to

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Type 2 Diabetes in Children and Adolescents on Atypical Antipsychotics

Cited by 15 publications

References 66 publications

Safety and Tolerability of Antipsychotic Drugs in Pediatric Patients: Data From a 1-Year Naturalistic Study

Safety and Tolerability of Antipsychotic Drugs in Pediatric Patients: Data From a 1-Year Naturalistic Study

Risk of Developing Type 2 Diabetes in Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Study

Medication‐induced diabetes mellitus

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