Waist Circumference is a Sensitive Screening Tool for Assessment of Metabolic Syndrome Risk in Children Treated with Second-Generation Antipsychotics

Abstract

Objective:To compare the prevalence of metabolic syndrome (MetS) and its components in second-generation antipsychotic (SGA)-treated and SGA-naive children; and to explore the utility of clinical markers, such as waist circumference (WC) and body mass index (BMI), as screening tools for MetS.Methods: Subjects were prospectively recruited from the Psychiatry Emergency Unit at British Columbia Children's Hospital. As part of a quality-assurance project, a metabolic monitoring protocol was implemented, including collection of anthropomorphic and laboratory data.Results: From January 2008 to February 2010, there were 117 SGA-treated and 217 SGA-naive children recruited. The overall prevalence of MetS was 19.0% (16/84; median treatment duration = 14 months) in SGA-treated and 0.8% (1/127) in SGA-naive children (OR 29.7; 95% CI 3.85 to 228.40, P < 0.001), with an increased prevalence of all components except high-density lipoprotein cholesterol (HDL-C), respectively: elevated WC (40.7% and 10.1%; P < 0.001); hypertriglyceridemia (33.7% and 18.8%; P = 0.01); impaired fasting glucose (12.5% and 0.7%; P = 0.005); and elevated blood pressure (41.2% and 16.5%; P < 0.001). SGA treatment was the strongest predictor of MetS (OR 19.2; 95% CI 2.30 to 160.44, P = 0.006) followed by male sex (OR 5.7; 95% CI 1.08 to 30.62, P = 0.04). Presence of abdominal obesity was more sensitive (92.9%) than BMI (68.8%), while fasting glucose of 5.6 mmol/L or more and HDL-C of 1.03mmol/L or less were most specific (94.1%) in correctly identifying MetS.Conclusions: SGA treatment confers a significantly increased risk for MetS over the long term. WC measurement is a simple and sensitive screening tool for determining MetS risk in SGA-treated children. These data highlight the dangers of SGA treatment and the importance of standardized metabolic monitoring using sex-and age-adjusted tables in this population.

A Population-Based Study of Antipsychotic Prescription Trends in Children and Adolescents in British Columbia, from 1996 to 2011

“…Notably, SGA prescriptions increased 18-fold during this time period. This is of great concern given the recent literature 7,8 demonstrating that SGAs can lead to serious metabolic side effects that may predispose these youth to an increased risk of cardiovascular disease in adulthood. [10][11][12][13] Our results are consistent with another recent Canadian study, 6 which documented a 4-fold increase in AP Our data revealed that the largest change in prescriptions was in 13-to 18-year-old males, with a 4.5-fold increase in AP prescriptions from 1996/97 to 2010/11.…”

“…5,6 The dramatic increase in off-label use of SGAs is of particular concern given the growing body of literature demonstrating that these medications may result in serious metabolic side effects, including weight gain, dyslipidemia, hypertension, type 2 diabetes, and metabolic syndrome in youth. 7,8 Further, obesity and metabolic dysregulation in childhood poses an increased risk for long-term complications in adulthood, including cardiovascular disease. [9][10][11][12][13] Despite the established risks of SGA treatment, limited data 6,14,15 currently exist describing AP prescription trends in Canadian children.…”

Second-Generation Antipsychotics Cause a Rapid Switch to Fat Oxidation That Is Required for Survival in C57BL/6J Mice

“…2 Additionally, the diagnoses for which SGAs are prescribed along with their overall utilization in adults and children have increased dramatically, [3][4][5] thus increasing the pool at risk. 6,7 It is currently unclear whether children, a population in which diabetes appears to be more difficult to treat, 8 are appropriately screened for these side effects. 9 Another issue is that the weight gain and metabolic side effects contribute to reduced compliance, increasing the risk of psychosis and the potential for reduced efficacy of subsequent SGA treatment.…”

Interaction between the Val158Met catechol-O-methyltransferase gene variant and second-generation antipsychotic treatment on blood pressure in children

“…[3][4][5] Recently, we and others have reported similar metabolic consequences in children and adolescents showing a higher prevalence of obesity/overweight, elevated blood pressure (BP) and dyslipidemia in SGA-treated compared with SGA-naive children. [6][7][8][9][10] Furthermore, these SGA-treatment-related side effects present rapidly with the onset of treatment but are not observed in all children. For example, a recent investigation reported that B21% of children prescribed SGAs became overweight/obese following only 11 weeks of treatment.…”