Children’s use of antipsychotics may increase risk of diabetes

Initiating antipsychotics may elevate a child’s risk not only for significant weight gain, but also for type 2 diabetes by nearly 50%, according to a study in JAMA Pediatrics. Moreover, among children who are also receiving antidepressants, the risk may double.

Researchers from The Children’s Hospital of Philadelphia’s (CHOP) PolicyLab published what is said to be the largest study to date documenting the significant risks to children’s health associated with prescription antipsychotics. Previous PolicyLab research showed that 1 in 3 youth receiving antidepressants in the Medicaid program were receiving an antipsychotic at the same time.

Traditionally, antipsychotics have been narrowly prescribed to children with a diagnosis of schizophrenia or bipolar disorder, or to those with significant developmental delays who were displaying aggressive behaviors that were potentially injurious to themselves or others. However, in recent years, these medications are increasingly being prescribed in the absence of strong supporting safety and efficacy data to treat healthier children and adolescents with disruptive behaviors, such as those who are diagnosed with attention deficit hyperactivity disorder (ADHD).

This was a retrospective national cohort study of 1.3 million Medicaid-enrolled youth aged 10 to 18 years between 2003 and 2007. Eligible youth with at least 1 mental health diagnosis were identified in each month of the study as second-generation antipsychotic initiators or non-initiators, based on whether they had a new prescription for a second-generation antipsychotic in that month, and then followed until diagnosis of diabetes or loss of Medicaid eligibility. Propensity weights were developed to balance observed demographic and clinical characteristics between exposure groups. Discrete failure time models were fit using weighted logistic regression to estimate the risk for incident type 2 diabetes between initiators and non-initiators of second-generation antipsychotics.

Overall, more than 25% of Medicaid-enrolled children receiving prescription medications for behavioral problems were prescribed antipsychotics by 2008, largely for less-severe disorders.

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Dr Rubin“The use of second-generation antipsychotics was associated with a 50% increase in the risk of developing type 2 diabetes,” according to David Rubin, MD, MSCE, the study's lead author and co-director of PolicyLab at CHOP. “Moreover, among youth who were receiving antidepressants when starting second-generation antipsychotic treatment, the risk for incident diabetes doubled. Finally, the study demonstrated that newer second-generation antipsychotics may not have a lower side-effect profile than risperidone, an older and frequently prescribed second-generation antipsychotics.”

These findings shed new light on the potential for serious adverse effects associated with the use of second-generation antipsychotics in children and adolescents, according to Dr Rubin.

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“Any policy implemented by a managed care organization or formulary manager regarding second-generation antipsychotic prescribing should include a thoughtful consideration of the risks and benefits of their use,” Rubin said. “While it is important to limit the numbers of children exposed to these medications and to carefully monitor exposed children for weight gain or abnormal lab tests, it is equally important to avoid imposing barriers that might restrict the use of these medications for children in crisis, for whom the benefit of the antipsychotic for acute management may still outweigh the risk.”

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Additionally, offering options for youth to obtain access to evidence-based counseling services, such as trauma-focused therapy, could provide an alternative to medication for some children, he added.

This national analysis adds to a literature of adverse events related to second-generation antipsychotic use.

“Particularly in the context of a rising trend of prescribing antipsychotics alongside other psychotropic medications, these results warrant continued scrutiny of the safety of prescribing antipsychotics to children and adolescents, both singly and concomitantly with other medications,” Dr Rubin said. “When prescribing second-generation antipsychotics in pediatric populations, the empirical evidence of efficacy of second-generation antipsychotic treatment must be carefully balanced against the potential risk of harm. Finally, these findings emphasize a need for best prescribing practices, which must include metabolic screening when prescribing second-generation antipsychotics to youth.”

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