In children and adolescents, treatment with “second-generation” antipsychotic drugs is associated with significant weight gain and increased cholesterol levels, researchers warn in the Journal of the American Medical Association this week.

In the US, children and adolescents with psychotic disorders, bipolar disorder, and other mental disorders are often treated with second-generation antipsychotic medications. Examples of these agents include aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal).

Increasingly, the side effects of these antipsychotic medications have “raised concern,” Dr. Christoph Correll and associates from North Shore-Long Island Jewish Health System, Glen Oaks, New York, note in their report.

The harmful effects of these drugs - such as weight gain, obesity, high blood pressure, and cholesterol and blood sugar abnormalities - are particularly worrisome during adolescence because they predict adult obesity, diabetes, and heart disease.

Correll’s team studied 272 children and adolescents aged 4 to 19 years old with mood disorders, schizophrenia, or disruptive or aggressive behavior who had not previously received antipsychotic medication. Fifteen patients who refused to participate or who did not take their antipsychotic medication as prescribed served as a comparison group.

Patients were treated with the antipsychotic medications aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks.

After a median of 10.8 weeks of treatment, weight increased by an average of 18.7 pounds in children taking olanzapine, by 13.4 pounds in those on quetiapine, by 11.7 pounds in those taking risperidone, and by 9.7 pounds in aripiprazole users, compared with minimal weight change of 0.4 pounds in the untreated comparison group.

“Each antipsychotic medication was associated with significantly increased fat mass and waist circumference,” the investigators report. “Altogether, 10 percent to 36 percent of patients transitioned to overweight or obese status within 11 weeks.”

The researchers also noted unhealthy changes in total cholesterol levels and triglycerides in children taking olanzapine and quetiapine and in triglycerides in children taking risperidone. Children taking quetiapine and olanzapine also showed increases in their blood sugar levels. Only aripiprazole was not associated with significant changes in these “metabolic” parameters.

Correll’s team warns that “the benefits of second-generation antipsychotic medications must be balanced against their cardiometabolic risks through a careful assessment of the indications for their use, consideration of lower risk alternatives, and proactive adverse effect monitoring and management.”

In an editorial published with the study, Drs. Christopher K. Varley and Jon McClellan at Seattle Children’s Hospital urge that “the widespread and increasing use of atypical antipsychotic medications in children and adolescents should be reconsidered.”

“Much of the support for (these) agents is provided by industry-sponsored investigations,” they write. “It is critical that large-scale, independently funded investigations be conducted to establish the long-term safety and benefit of atypical antipsychotic medications in children and adolescents.”

SOURCE: Journal of the American Medical Association, October 28, 2009.