Children and adolescents who started on any one of four psychiatric drugs known as "atypical antipsychotics" packed on a significant amount of weight, new research has found. And three of the four psychiatric medications under study came with metabolic side effects that will dramatically boost a child's likelihood of developing cardiovascular disease, according to a study published Tuesday in the Journal of the American Medical Assn.
Patients taking their first-ever course of drugs marketed as Abilify, Risperdal, Seroquel and Zyprexa experienced weight gains ranging from about 9.7 pounds for Abilify to 18.7 pounds for Zyprexa. (Seroquel users gained about 13.2 pounds and Risperdal users gained about 11.7 pounds over 12 weeks. A comparison group of children with a diagnosis of severe mental illness but who were not on the medications gained less than a half-pound in the course of the study.)
Young patients on Risperdal, Seroquel and Zyprexa all experienced a significant increase in their triglycerides, and those taking Zyprexa and Seroquel had a surge in their overall cholesterol readings. Those taking Abilify registered dramatic changes in body composition, but no metabolic changes that reached the level of statistical significance accepted by medical researchers.
Among the 205 patients who completed the study, it was rare for researchers to see metabolic syndrome or diabetes develop in the 12 weeks of treatment they observed. But they took note of two kinds of changes in subjects that were ominous: first, they noted significant changes in the children's fat mass and waist circumference measures--which predict the development of heart disease in the general population and metabolic syndrome in adults taking antipsychotic medicines; and second, they recorded significant changes in many of the children's triglycerides and in the ratios of triglycerides to HDL cholesterol--both considered a reliable predictor of insulin resistance to come.
The latest study is the largest to date focusing on young patients taking one of the new-generation antipsychotics for the first time. Its results were hailed as "timely and sobering" in an editorial accompanying the study's publication. It comes against a backdrop of rapidly expanding use of these drugs, and their growing use among children as young as 5. The Food and Drug Administration is currently considering whether it to accept the recommendation of a panel of outside experts and approve three of the four drugs for use by children diagnosed with schizophrenia and/or bipolar disorder.
JAMA's editorial suggests that such a step might be ill-advised.
"These results challenge the widespread use of atypical antipsychotic medications in youth," wrote University of Washington, Seattle, child psychiatrists Christopher K. Varley and Jon McClellan.
The commenting physicians warned that the change in children's cholesterol levels and insulin resistance readings observed after only 12 weeks of treatment "portends severe long-term metabolic and cardiovascular sequelae." While physicians expanded their use of the drugs because they were "widely touted as being more effective and safer" than older psychiatric drugs, that belief "should be reconsidered," Varley and McClellan wrote.
Several earlier studies of these antipsychotic medications have documented weight gain, changes in body composition and measures of metabolic function. But this study's findings are the most dramatic so far to come to light. The researchers suggested that earlier studies--many of them conducted under the sponsorship of drug makers--may have understated children's weight gain on the drugs by including many subjects who had taken earlier courses of antipsychotic medicine, and thus already had experienced drug-connected weight gain. For all the subjects followed in this study, this was the first time they had taken any drug classified as an antipsychotic medication.
Scattered in academic medical centers across New York state, all the researchers were sponsored by grants from the National Institutes of Health.
-- Melissa Healy