NEW YORK – With new national data finding that 17% of the country’s youngsters are obese, physicians who treat children with antipsychotics face even tougher medication choices.
Because many of the drugs are tied to increases in weight and obesity-driven diseases, it’s not hard to see the looming metabolic train wreck, Dr. Christoph U. Correll said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.
The newest NHANES (National Health and Nutrition Survey), released in January, found that more than one-third of U.S. adults and almost 17% of youth were classified as obese in 2009-2010.
"We are now seeing obese children with type 2 diabetes, and we know that this disease has the same 8-year risk as a myocardial infarction for [another] heart attack," said Dr. Correll of the Zucker Hillside Hospital in Glen Oak, N.Y. "We will see obese children who will not outlive their parents, and we must admit that our treatments are contributing to this."
Studies agree that many antipsychotic medications are associated with significant weight gain, much of that leading to metabolic syndrome, Dr. Correll said. A 2011 meta-analysis of 3,000 children found that those taking olanzapine gained almost 4 kg within just 1 month of starting the medication (Euro. Psychiatry 2011:26:144-58). Quetiapine was associated with a gain of 2 kg over 4 weeks, and risperidone with a gain of 2 kg over 7 weeks. Patients taking aripiprazole gained 1 kg over 6 weeks, whereas those taking a placebo had no weight change.
"We will see obese children who will not outlive their parents, and we must admit that our treatments are contributing to this."
This phenomenon is directly related to the onset of metabolic syndrome, and its associated cardiovascular risks of lipid abnormalities and hypertension, Dr. Correll said. "The longer you treat, the higher are these rates. And the longer you have cardiovascular risk factors, the greater your chance of death."
A 2006 study illustrates his point. By 10 years of treatment, 21% of patients had metabolic syndrome; by 20 years of treatment, 34%, and after 20 years, 39%.
Age played a significant role, as expected, but a significant difference was found between the general population and patients taking the drugs. Among patients aged 35-45 years, 35% had metabolic syndrome, compared with 6.5% of nonpatients. By 55 years, the prevalence had doubled in the general population, to about 14%, while it increased significantly less in patients, to 38%.
"This shows that we are shifting the metabolic burden to earlier in life. These patients are prematurely metabolically demented, and we are doing this by not taking care of their weight and metabolic problems."
This leaves psychiatrists on the horns of a dilemma, Dr. Correll said. Patients need treatment, but the drugs come with a high physiological price. To decrease patients’ exposure to metabolic risks, he advises starting treatment with the lowest metabolically driven medications, and moving to other drugs only if the less risky ones aren’t controlling symptoms.
Studies suggest that, in most patients, olanzapine confers the greatest risk of weight gain, and risperidone the lowest. Lurasidone is doing "quite well" in adult studies, as far as weight gain goes (Drugs Today [Barc.] 2011;47:807-16), but it has not been examined in children or adolescents. "I think this is something we as pediatric psychiatrists should be trying to get our hands on," Dr. Correll said.
A newly published, randomized trial suggests that valproate might change some of the metabolic activity that drives weight gain in patients taking antipsychotic medications.
Patients with treatment-resistant schizophrenia, schizoaffective disorder, or bipolar disorder were randomized to olanzapine or risperidone alone, or to either of the drugs plus valproate as a mood stabilizer. Every one of those taking olanzapine plus valproate experienced significant weight gains, whereas the weight gain occurred in 60% of those taking olanzapine alone.
Weight gain was less common in both risperidone groups. But the addition of valproate seemed to enhance risperidone’s weight-neutral effect: Some 15% of those taking the combination gained significant amounts of weight – significantly fewer than the 30% who gained weight on risperidone alone (J. Clin. Psychiatry 2011;72:1602-10).
The same pattern held with other metabolic measures, including changes in body mass index, glycosylated hemoglobin, total cholesterol, and the triglyceride/HDL cholesterol ratio.
The findings point out just how much remains unknown about the metabolic effects of antipsychotic medications. For now, Dr. Correll said, the best path is to start with the lowest metabolically active drug appropriate for that patient, and closely monitor any metabolic changes.