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Newer Antipsychotics Raise Diabetes Risk in Youth


June 10, 2012 (Philadelphia, Pennsylvania) — Second-generation antipsychotics (SGAs), particularly ziprasidone, raise the risk for type 2 diabetes (T2D) in children and adolescents, according to research presented here at the American Diabetes Association (ADA) 72nd Scientific Sessions.
Many studies have shown that SGAs can increase diabetes risks in adults, but "children have not been explored that much," Avnish Tripathi, MD, MPH, a doctoral candidate at the University of South Carolina School of Public Health, Columbia, who presented the research, told Medscape Medical News.
The researchers conducted a study of more than 4000 patients 17 years and younger who were served through the South Carolina State Medicaid Program between 1996 and 2006, and who had been newly prescribed at least 1 of the following SGAs during that time: aripiprazole, ziprasidone, quetiapine, risperidone, and olanzapine.
The study included a 24-month "SGA-free" baseline period immediately before the first SGA was prescribed. The researchers defined incidence of T2D as 2 or more initial service encounters at least 30 days apart, marked by International Classification of Diseases, Ninth Revision, codes for T2D. The researchers used similar criteria to establish comorbid conditions such as obesity, dyslipidemia, and hypertension.
The study included 4140 patients (median age, 11 years; interquartile range, 4 - 11 years), of whom 176 participants (4.3%) were diagnosed with new-onset T2D.
The researchers conducted Cox proportional hazards analysis with time-dependent covariates and found increased risk for T2D in females (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.30 - 2.44); African Americans (HR, 1.52; 95% CI, 1.07 - 1.25), overweight or obese individuals (HR, 4.19; 95% CI, 2.87 - 6.11), and patients with dyslipidemia (HR, 3.33; 95% CI, 1.76 - 6.30).
Compared with patients with no exposure to SGAs, the investigators also noted increased risk associated with use of aripiprazole (HR, 2.92; 95% CI, 1.08 - 7.90) or ziprasidone (HR, 3.56; 95% CI, 1.61 - 7.89). Mood stabilizers also increased risk (HR, 1.64; 95% CI, 1.13 - 2.37) compared with those with no exposure.
A multivariable marginal structural model indicated a higher causal association of overweight/obesity (HR, 5.59; 95% CI, 2.71 - 11.51) and ziprasidone (HR, 5.12; 95% CI, 1.15 - 22.70).
The reliance on administrative Medicaid data is a limitation, but it also reflects real-world situations, Dr. Tripathi acknowledged. "You are able to account for all kinds of co-morbidities and co-prescriptions in a real-life setting. You don't have good control over the data, but it gives you a hypothesis for better laid-out studies."
It is difficult to tease out the effect of different drugs on diabetes risk factors because the children are often prescribed a variety of medications, including antipsychotics, antidepressants, and mood stabilizers. "It means that this is a vulnerable population. There should be an awareness [of potential diabetes risk]. For a kid who is obese, [healthcare providers] should look at interventions for obesity, screen for dyslipidemia, and perhaps move to a better SGA," said Dr. Tripathi.
In the past 10 to 15 years, SGAs have been prescribed "indiscriminately" to adults for a variety of disorders, according to Ali Rizvi, MD, professor of medicine at the University of South Carolina School of Medicine, Columbia, and a study coauthor. "Now, we're realizing that we've gone overboard and haven't been cognizant of the side effect profiles. We certainly don't want that repeated in the pediatric population," Dr. Rizvi told Medscape Medical News.
The research could have important long-term implications, according to Hsin-Chieh Yeh, PhD, assistant professor internal medicine at Johns Hopkins University School of Medicine, Baltimore, Maryland, who moderated the session.
"It's a pediatric population, and they have a very long life expectancy. If this [effect] is true, that will be important for society in terms of the cost of medical care and the burden to the population," Dr. Yeh told Medscape Medical News.
Dr. Tripathi and Dr. Yeh have disclosed no relevant financial relationships.
American Diabetes Association (ADA) 72nd Scientific Sessions. Abstract #17-OR. Presented June 8, 2012.

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