In the Journals

Antipsychotic use could lead to weight gain, insulin sensitivity in youth

Researchers found that children who received 12 weeks of treatment with antipsychotic medications experienced adverse changes in adiposity and insulin sensitivity, both of which often contribute to the development of early-onset type 2 diabetes, cardiovascular disease and other illnesses tied to early death.

“Although youths with [ADHD and disruptive behavior disorder] might benefit from antipsychotic treatment, careful consideration of risks and benefits is warranted,” Ginger E. Nicol, MD, from the department of psychiatry, Washington University School of Medicine in St. Louis, and colleagues wrote in JAMA Psychiatry. “That we know of, direct measures of adiposity and insulin sensitivity have not been used together as primary outcomes in any published studies of prospective randomized antipsychotic treatment in youth, limiting understanding of key treatment-induced risks.”

In this randomized clinical trial of youths aged 6 to 18 years, researchers examined the metabolic effects of first exposure to antipsychotic medications commonly used in children with disruptive behavioral disorders via body composition and insulin sensitivity assessments.

Antipsychotic-naive children who were diagnosed with at least one psychiatric disorder and clinically significant aggression received 12 weeks of treatment with either oral aripiprazole (n = 49), olanzapine (n = 46) or risperidone (n = 49). Nicol and colleagues measured percentage total body fat using dual-energy X-ray absorptiometry (DXA) and insulin sensitivity in muscle using hyperinsulinemic clamps with stable isotopically labeled tracers as primary outcomes. Secondary outcomes included abdominal adiposity and hepatic tissue insulin sensitivity.

Weight Loss Scale
Study findings showed that children who received 12 weeks of treatment with antipsychotic medications experienced adverse changes in adiposity and insulin sensitivity.
Source:Shutterstock.com

The analysis included 144 participants, 43 of whom were overweight or obese at baseline. Results showed that total body fat increased by 1.18% among children who received risperidone, 4.12% among those who received olanzapine and 1.66% among those who received aripiprazole from baseline to week 12. The percentage total body fat was greater for those receiving olanzapine than risperidone or aripiprazole (P < .001). All treatments resulted in behavioral improvements.

During treatment, insulin-stimulated change in glucose rate of disappearance rose by 2.3% for risperidone, whereas it dropped by 29.34% for olanzapine and by 30.26% for aripiprazole; however, there was no significant difference across medications. Moreover, insulin sensitivity also dropped in the pooled study sample during the 12 weeks of treatment (P < .001). In addition, abdominal fat increased from baseline to week 12, with greater subcutaneous fat increase observed in those who received olanzapine (P = .003).

“The present results inform risk-benefit considerations for the use of antipsychotics in children and adolescents. ... Future studies should explore clinical indicators of risk,” Nicol and colleagues wrote. “The potential psychiatric benefits of antipsychotic use in this population, evident in this trial and others, should be carefully weighed against the potential for childhood onset of abdominal obesity and insulin resistance that — compared with adult onset — further increases long-term risk for [type 2 diabetes], cardiovascular disease, and related conditions.”

Clinicians treating children with antipsychotic drugs should prescribe medications with low-to-moderate metabolic risk, avoid olanzapine and aim for the shortest necessary treatment duration in the case of off-label use, Marc De Hert, MD, PhD, and Johan Detraux, MPsy, of the University Psychiatric Centre, Katholieke Universiteit Leuven in Belgium, wrote in a related opinion.

“To avoid a lack of clarity and consensus as to where the responsibility of primary caregivers and psychiatrists for this monitoring lies, we suggest that specialist mental health teams should assume lead responsibility for the first 12 months or until the patient’s condition has stabilized,” De Hert and Detraux recommended. “Thereafter, primary care clinicians should assume that responsibility unless there are particular reasons that this responsibility should remain with secondary care.” by Savannah Demko

Disclosures: Nicol reports funding from Alkermes PLC, the Center for Brain Research in Mood Disorders, NIMH, Otsuka America Pharmaceutical Inc and the Sidney R. Baer Jr Foundation. Please see the study for all other authors’ relevant financial disclosures. Detraux reports partial support from the Janssen Academy. De Hert reports no relevant financial disclosures.

Researchers found that children who received 12 weeks of treatment with antipsychotic medications experienced adverse changes in adiposity and insulin sensitivity, both of which often contribute to the development of early-onset type 2 diabetes, cardiovascular disease and other illnesses tied to early death.

“Although youths with [ADHD and disruptive behavior disorder] might benefit from antipsychotic treatment, careful consideration of risks and benefits is warranted,” Ginger E. Nicol, MD, from the department of psychiatry, Washington University School of Medicine in St. Louis, and colleagues wrote in JAMA Psychiatry. “That we know of, direct measures of adiposity and insulin sensitivity have not been used together as primary outcomes in any published studies of prospective randomized antipsychotic treatment in youth, limiting understanding of key treatment-induced risks.”

In this randomized clinical trial of youths aged 6 to 18 years, researchers examined the metabolic effects of first exposure to antipsychotic medications commonly used in children with disruptive behavioral disorders via body composition and insulin sensitivity assessments.

Antipsychotic-naive children who were diagnosed with at least one psychiatric disorder and clinically significant aggression received 12 weeks of treatment with either oral aripiprazole (n = 49), olanzapine (n = 46) or risperidone (n = 49). Nicol and colleagues measured percentage total body fat using dual-energy X-ray absorptiometry (DXA) and insulin sensitivity in muscle using hyperinsulinemic clamps with stable isotopically labeled tracers as primary outcomes. Secondary outcomes included abdominal adiposity and hepatic tissue insulin sensitivity.

Weight Loss Scale
Study findings showed that children who received 12 weeks of treatment with antipsychotic medications experienced adverse changes in adiposity and insulin sensitivity.
Source:Shutterstock.com

The analysis included 144 participants, 43 of whom were overweight or obese at baseline. Results showed that total body fat increased by 1.18% among children who received risperidone, 4.12% among those who received olanzapine and 1.66% among those who received aripiprazole from baseline to week 12. The percentage total body fat was greater for those receiving olanzapine than risperidone or aripiprazole (P < .001). All treatments resulted in behavioral improvements.

During treatment, insulin-stimulated change in glucose rate of disappearance rose by 2.3% for risperidone, whereas it dropped by 29.34% for olanzapine and by 30.26% for aripiprazole; however, there was no significant difference across medications. Moreover, insulin sensitivity also dropped in the pooled study sample during the 12 weeks of treatment (P < .001). In addition, abdominal fat increased from baseline to week 12, with greater subcutaneous fat increase observed in those who received olanzapine (P = .003).

“The present results inform risk-benefit considerations for the use of antipsychotics in children and adolescents. ... Future studies should explore clinical indicators of risk,” Nicol and colleagues wrote. “The potential psychiatric benefits of antipsychotic use in this population, evident in this trial and others, should be carefully weighed against the potential for childhood onset of abdominal obesity and insulin resistance that — compared with adult onset — further increases long-term risk for [type 2 diabetes], cardiovascular disease, and related conditions.”

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Clinicians treating children with antipsychotic drugs should prescribe medications with low-to-moderate metabolic risk, avoid olanzapine and aim for the shortest necessary treatment duration in the case of off-label use, Marc De Hert, MD, PhD, and Johan Detraux, MPsy, of the University Psychiatric Centre, Katholieke Universiteit Leuven in Belgium, wrote in a related opinion.

“To avoid a lack of clarity and consensus as to where the responsibility of primary caregivers and psychiatrists for this monitoring lies, we suggest that specialist mental health teams should assume lead responsibility for the first 12 months or until the patient’s condition has stabilized,” De Hert and Detraux recommended. “Thereafter, primary care clinicians should assume that responsibility unless there are particular reasons that this responsibility should remain with secondary care.” by Savannah Demko

Disclosures: Nicol reports funding from Alkermes PLC, the Center for Brain Research in Mood Disorders, NIMH, Otsuka America Pharmaceutical Inc and the Sidney R. Baer Jr Foundation. Please see the study for all other authors’ relevant financial disclosures. Detraux reports partial support from the Janssen Academy. De Hert reports no relevant financial disclosures.