Metabolic Side Effects of Risperidone in Children and Adolescents With Early-Onset Schizophrenia

Abstract

Sir: Atypical antipsychotics have a favorable risk/benefit profile in early-onset schizophrenia,1 but their endocrine and metabolic side effects (weight gain, obesity, and related metabolic abnormalities, such as hyperglycemia and dyslipidemia) are of particular concern,2 especially with children.3,4 These side effects may evolve to a metabolic syndrome with a high-risk state for future cardiovascular morbidity and mortality.5 Sex- and age-adjusted body mass index (BMI) percentiles and BMI z scores are crucial to assess weight gain and obesity in children and adolescents.6 Numerous studies have assessed weight gain during antipsychotic treatment,7 yet these studies are limited because of their short duration and because of their methodology: indeed, adjusted BMI percentiles and BMI z scores were calculated in only 1 study.8 Method. This pilot study focuses on the metabolic effects of risperidone in children and adolescents up to 16 years of age. Patients included in the study were referred to our Department of Child and Adolescent Psychiatry at the University Hospital Center of Lille for early-onset schizophrenia (according to the Schedule for Affective Disorders and Schizophrenia for School Age Children for DSM-IV9) from June 2005 to June 2007. They had received no antipsychotic treatment prior to their inclusion. Weight, height, waist circumference, blood pressure, fasting triglyceride levels, fasting total and high-density lipoprotein (HDL) cholesterol levels, and fasting glucose levels were measured. Sex- and age-related BMI percentiles and adjusted BMI z scores were obtained from tables from the Centers for Disease Control.10 Statistical analyses were performed using the SAS software (SAS Institute, Inc., Cary, N.C.). All p values < .05 were considered statistically significant. The linear mixed model was used to analyze repeated measurements. This study has been approved by the regional Comite de Protection des Personnes Nord-Quest IV. Results. Fifteen schizophrenic adolescents (11 males, 4 females) aged 11 to 16 years (mean = 13.3 years, SD = 2.4 years) were included. Risperidone was given from 1 mg/day to a maximum of 6 mg/day. Data were obtained for 10 patients at month 3, for 8 patients at month 6, and for 5 patients at month 12 of follow-up. Statistical analysis shows a significant link between prescription of risperidone in early-onset schizophrenia and increases of BMI (p = .043), sex- and age-adjusted BMI percentile (p = .033), and BMI z scores (p = .025). Clinically, one 15-year-old male, receiving risperidone up to 6 mg/day, presented with hyperprolactinemia-induced gynecomastia after 6 months of follow-up (neurologic examination was normal), while his BMI increased from 16.2 kg/m2 to 28 kg/m2 (BMI z score increased from –0.97 to 1.95). Furthermore, one 14-year-old female, receiving 2 mg/day of risperidone, presented a 100 mg/dL increase of fasting total cholesterol (up to 248 mg/dL, normal range: 150–200 mg/dL) during the first 3 months of treatment, along with just a small increase of her BMI (from 17.1 kg/m2 to 18.2 kg/m2). At 6 months of follow-up, her dose of risperidone was decreased to 1 mg/day, and within 3 months her total cholesterol level also decreased to 224 mg/dL. Glucose, cholesterol, and blood pressure remained at normal levels for all the other patients. Despite the limited number of children included, our results confirm a strong link between prescription of risperidone in early-onset schizophrenia and risk of obesity. Clinicians and caregivers need to be aware of the potential endocrine and metabolic adverse effects of atypical antipsychotics and systematically ask for family history of metabolic disorder, lifestyle, diet, and habits. Alternative treatment should be considered in some cases.11 With adolescents, the sole monitoring of weight gain, and even of BMI, underestimates the gain of corpulence. One methodological implication of our study is that adjusted BMI z scores seem to be the best suited to assess long-term drug-induced weight gain. Jean-Louis Goeb, M.D., Ph.D. Sophie Marco, M.D. Department of Child and Adolescent Psychiatry, University Hospital Center of Lille Alain Duhamel, M.D. Department of Biostatistics, University of Lille 2 Renaud Jardri, M.D. Geraldine Kechid, M.D. Department of Child and Adolescent Psychiatry, University Hospital Center of Lille Regis Bordet, M.D., Ph.D. Department of Pharmacology, University of Lille 2 Pierre Delion, M.D., Ph.D. Department of Child and Adolescent Psychiatry Pierre Thomas, M.D., Ph.D. Department of Psychiatry, University Hospital Center of Lille, Lille, France