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 Comité 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 Goëb, 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
Régis 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
Footnotes
This pilot study, promoted by the University Hospital Center of Lille, is supported by a public grant: Programme Hospitalier de Recherche Clinique PHRC 2006, “Antipsychotics and Metabolic Disorders,” to Dr. Thomas.
Dr. Bordet is a consultant to Genfit and has served on the speakers/advisory boards for Lundbeck, Janssen, Cilag, Bristol-Myers Squibb, Sanofi Aventis, and Pfizer. Drs. Goëb, Marco, Duhamel, Jardri, Kechid, Delion, and Thomas report no additional financial affiliations or other relationships relevant to the subject of this letter.
The authors thank Frank Bonelli, M.D., Department of Child and Adolescent Psychiatry, University Hospital Center of Lille, for assistance with translation. Dr. Bonelli has no financial or other relationships relevant to the subject of this letter.
REFERENCES
- 1.Masi G, Mucci M, Pari C. Children with schizophrenia: clinical picture and pharmacological treatment. CNS Drugs. 2006;20(10):841–866. doi: 10.2165/00023210-200620100-00005. [DOI] [PubMed] [Google Scholar]
- 2.Correll CU, Carlson HE. Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2006 Jul;45(7):771–791. doi: 10.1097/01.chi.0000220851.94392.30. [DOI] [PubMed] [Google Scholar]
- 3.Stigler KA, Potenza MN, Posey DJ, et al. Weight gain associated with atypical antipsychotic use in children and adolescents: prevalence, clinical relevance, and management. Pediatr Drugs. 2004;6(1):33–44. doi: 10.2165/00148581-200406010-00003. [DOI] [PubMed] [Google Scholar]
- 4.Newcomer JW. Metabolic risk during antipsychotic treatment. Clin Ther. 2004 Dec;26(12):1936–1946. doi: 10.1016/j.clinthera.2004.12.003. [DOI] [PubMed] [Google Scholar]
- 5.Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med. 2004 Jun;350(23):2362–2374. doi: 10.1056/NEJMoa031049. [DOI] [PubMed] [Google Scholar]
- 6.Correll CU. Metabolic side effects of second-generation antipsychotics in children and adolescents: a different story?[ASCP Corner] J Clin Psychiatry. 2005 Oct;66(10):1331–1332. doi: 10.4088/jcp.v66n1018. [DOI] [PubMed] [Google Scholar]
- 7.Vieweg WV, Sood AB, Pandurangi A, et al. Newer antipsychotic drugs and obesity in children and adolescents: how should we assess drug-associated weight gain? Acta Psychiatr Scand. 2005 Mar;111(3):177–184. doi: 10.1111/j.1600-0447.2004.00444.x. [DOI] [PubMed] [Google Scholar]
- 8.Correll CU, Parikh UH, Mughal T. Body composition changes associated with second generation antipsychotics. Biol Psychiatry. 2005;57(suppl 8):36. [Google Scholar]
- 9.Ambrosini PJ. Historical development and present status of the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS) J Am Acad Child Adolesc Psychiatry. 2000 Jan;39(1):49–58. doi: 10.1097/00004583-200001000-00016. [DOI] [PubMed] [Google Scholar]
- 10.2000 CDC Growth Charts: United States Centers for Disease Control, National Center for Health Statistics Web site. Available at: http://www.cdc.gov/growthchartsAccessibility verified June 13, 2008 [Google Scholar]
- 11.Jardri R, Lucas B, Delevoye-Turrell Y, et al. An 11-year-old boy with drug resistant schizophrenia treated with temporo-parietal rTMS. Mol Psychiatry. 2007 Apr;12(4):320. doi: 10.1038/sj.mp.4001968. [DOI] [PubMed] [Google Scholar]