Source: Bobo WV, Cooper WO, Stein CM, et al. Antipsychotics and the risk of type 2 diabetes mellitus in children and youth. JAMA Psychiatry. 2013; 70(10): 1067– 1075; doi: 10.1001/jama-psychiatry.2013.2053Investigators from multiple US institutions conducted a retrospective study to assess the association between recent initiation of antipsychotic medication and type 2 diabetes mellitus (T2DM) in youth. For the study, they abstracted data from the computerized files of the Tennessee Medicaid program, the statewide hospital discharge database, and birth certificates. The study cohort included children and youth between 6 and 24 years old who were enrolled in the Tennessee Medicaid program for at least 1 year between 1996 and 2007 and started on an antipsychotic medication no more than 90 days prior to the study period. Controls included youth started on a psychotropic drug other than an antipsychotic during the same time period. Participants with T2DM were defined by either having diabetes listed as a primary hospital discharge diagnosis or by an outpatient diagnosis of diabetes combined with a prescription for an antidiabetic medication. Control and study cohort participants were matched for multiple characteristics including age, race, and gender. Rates of T2DM in the 2 cohorts were compared.The study cohort included 28,858 youth who had recently initiated antipsychotic therapy and 14,429 controls who had recently initiated a psychotropic drug other than an antipsychotic. The risk for T2DM was 3 times greater in the study group than the control group (Hazard Ratio [HR] = 3.03; 95% CI, 1.73–5.32). This risk was apparent as early as the first year after antipsychotic initiation (HR = 2.49; 95% CI, 1.27–4.88). The risk for T2DM remained elevated up to a year following the discontinuation of antipsychotic drug use (HR = 2.57; 95% CI, 1.34–4.91). The effect was highly dependent on cumulative dose. Similar results were obtained when limiting the age range of analysis to those 6 to 17 years old.The investigators acknowledge that obesity was not controlled for and could have affected the results. They conclude that there is a significantly increased risk for T2DM with antipsychotic initiation in youth and continued risk even after discontinuation.Drs Schreiber and Malas have disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Antipsychotic medication use in children and adolescents has increased sixfold within the past 20 years with a near 20-fold increase in second-generation antipsychotic use.1,2 Increasingly, second-generation antipsychotics are being prescribed at younger ages for diagnoses such as depressive disorders, anxiety disorders, and oppositional defiant disorder.1,2 Data from prior reports and this study indicate that second-generation antipsychotic use in youth imparts a two- to threefold risk of developing T2DM or obesity, along with an increased risk of developing dyslipidemia, hypertension, and metabolic syndrome.2,3 Among youth, 11% to 36% will develop weight gain within a year of starting a second-generation antipsychotic.2Despite the metabolic and cardiovascular risks associated with prolonged second-generation antipsychotic use in children and adolescents, there are clear benefits to their use. For some rare disorders, such as bipolar disorder or a first psychotic break, there are strong data to support the use of these medications.2 Among some children with intellectual disability or autism, a second-generation antipsychotic may be the only medication that effectively manages their aggression, allowing them to engage and function in the community.2Recognizing the significant risk of cardiovascular and metabolic sequelae with antipsychotic use, the American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, and North American Association for Obesity developed guidelines for prescribing and monitoring antipsychotic medications.4 These guidelines include obtaining a personal and family history of obesity, T2DM, dyslipidemia, hypertension, and heart disease. Baseline measures should include weight, height, waist circumference, blood pressure, fasting blood glucose, and fasting lipids. Recommended follow-up includes repeating weight and waist circumference at 4, 8, and 12 weeks and then quarterly. Blood pressure, fasting glucose, and fasting lipids should be measured 12 weeks after starting an antipsychotic. Blood pressure, fasting glucose, waist circumference, and Abnormal Involvement Movement Scale testing should be conducted 1 year after the start of treatment.Given the rapid increase in the use of antipsychotics and the significant and severe long-term sequelae related to chronic antipsychotic use, pediatricians should be familiar with the indications, dosing, and monitoring of second-generation antipsychotics and work collaboratively with psychiatrists in order to use antipsychotic medications judiciously.