Cardiometabolic Risk of Second-Generation Antipsychotics During First-Time Use in Children and Adolescents

By Christoph U. Correll, P. Manu, V. Olshanskiy, B. Napolitano, J. Kane, A. Malhotra. Journal of the American Medical Association (JAMA), 2009

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Context Cardiometabolic effects of second-generation antipsychotics (SGAs) are concerning, but have been insufficiently studied in antipsychotic-naïve and pediatric patients. Objectives To study SGAs effects on body composition and metabolic parameters, unconfounded by prior antipsychotic exposure. Design Three-month, non-randomized Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) cohort study, conducted 12.2001–09.2007. Setting Semi-urban, tertiary care, academic inpatient and outpatient services in Queens, New York, with a 4.5 million people catchment area. Patients Of 505 youth, aged 4–19 (mean age: 13.9±3.6) years with ≤1 week antipsychotic exposure, 338 (66.9%) were enrolled. Of these, 272 (80.5%) had ≥1 post-baseline assessment forming the final sample, and 205 (61.7%) completed the study. Patients had mood spectrum (n=130, 47.8%), schizophrenia spectrum (n=82, 30.1%) and disruptive/aggressive behavior spectrum disorders (n=60, 22.1%). Fifteen refusing/non-adherent patients served as a comparison group. Interventions 12-week treatment with aripiprazole, olanzapine, quetiapine or risperidone. Main Outcome Measures Body composition (weight, Body Mass Index percentile/z-score, fat mass, waist circumference), and fasting glucose and lipid parameters. Results Weight increased by 19.0(95% Confidence Interval:16.4, 21.5)lbs=15.2(13.2, 17.2)% with olanzapine (N=45), 13.5(10.9, 16.0)lbs=10.4(8.5, 12.3)% with quetiapine (N=36), 11.9(10.7, 13.1)bs=10.4(9.4, 11.3)% with risperidone (N=135), and 9.9(8.2, 11.5)lbs=8.1(7.0, 9.5)% with aripiprazole (N=41). Comparison subjects (N=15) changed weight minimally: 0.4(−2.3, 3.2)lbs=0.7(−1.3, 2.6)%. Weight gain ≥7% occurred in 84.4% (n=38) of patients on olanzapine, 64.4% (n=87) on risperidone, 58.4% (n=24) on aripiprazole, 55.6% (n=20) on quetiapine, and 0% of comparison subjects. With olanzapine, cholesterol (p<.001), triglycerides (p=0.002), non-HDL-cholesterol (p<.001), triglyceride/HDL ratio (p=0.002), glucose (p=0.02), insulin (p=0.02), and HOMA-IR (p=0.03) increased significantly. With quetiapine, cholesterol (p<0.05), triglycerides (p=0.01), non-HDL-cholesterol (p=0.03), and triglyceride/HDL ratio (p=0.004) increased significantly. With risperidone, triglycerides (p=0.04) increased significantly. Metabolic baseline-to-endpoint changes were non-significant with aripiprazole and comparison subjects. Dyslipidemia developed in 28.9% (n=13), 19.4% (n=26), 8.8% (n=3), and 7.3% (n=3) of youth on olanzapine, risperidone, quetiapine and aripiprazole, and 6.7% (n=1) of comparison subjects (p=0.03), while acquired insulin resistance (HOMA-IR>4.39: 2.9%–17.8%) and metabolic syndrome (0%–6.5%) were relatively rare in this short-term study. Conclusions First time SGA use was associated with significant weight gain with each medication. Metabolic changes varied among the 4 antipsychotics.

Subfields: Pediatrics, Perinatology and Child Health, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/4c0f7c48d1d250b5848955a098501dd4202535d9

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In Psychiatry and Mental health

  1. Marc A. F. De Hert
  2. Christoph U. Correll
  3. Hans-Jürgen Möller

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