Children and adolescents rapidly gain substantial weight on a short course of the atypical antipsychotic medications aripiprazole, olanzapine, quetiapine, and risperidone, according to a report in the JAMA.
Up to 36% of patients in a study of 272 children and adolescents transitioned to overweight or obese status within 11 weeks, and many showed significant abnormalities in lipid profiles and metabolic measures, said Dr. Christoph U. Correll of Zucker Hillside Hospital, Glen Oaks, N.Y., and his associates.
The researchers investigated the cardiometabolic effects of atypical antipsychotic agents because they are “commonly and increasingly prescribed to children and adolescents in the United States as first-line treatment for psychotic disorders, bipolar disorder,” and a widening variety of nonpsychotic mental disorders.
Yet, they have been linked to weight gain, hypertension, lipid abnormalities, and glucose abnormalities that are a particular concern during development “because they predict adult obesity, the metabolic syndrome, cardiovascular morbidity, and malignancy,” the researchers wrote.
Until now, investigators have been unable to tease out the cardiometabolic effects of atypical antipsychotics in children because the agents have only been studied in subjects already exposed to a variety of other antipsychotic medications.
In an editorial accompanying the report, Dr. Christopher K. Varley and Dr. Jon McClellan of Seattle Children's Hospital said, “the development of clinically significant hyperlipidemias and insulin resistance after only 12 weeks of treatment portends severe long-term metabolic and cardiovascular sequelae.
“These results challenge the widespread use of atypical antipsychotic medications in youth.”
When first introduced, atypicals were widely touted as more effective and safer than older neuroleptic agents, which eased the physician reticence about prescribing these medications for young patients, they wrote. Before this, traditional antipsychotic medications were far less commonly prescribed for disruptive behavioral disorders, they noted (JAMA 2009;302:1811–2). Much of the data supporting the use of these agents have been provided by industry-sponsored research. “Medical treatment should be dictated by empirical data rather than by anecdote, assumptions, or marketing strategies,” they commented.
Dr. Correll and his colleagues assessed patients aged 4–19 years who were naive to previous antipsychotic therapy and were participating in a cohort study of pediatric psychotic, mood, or aggressive spectrum disorders.
For comparison, they assessed a control group of 15 similar participants who either refused or immediately discontinued atypical antipsychotic agents.
After a median of 11 weeks, all four drugs were associated with weight gain: an average of 8.5 kg for the 45 patients taking olanzapine, 6.1 kg for the 36 patients taking quetiapine, 5.3 kg for the 135 patients taking risperidone, and 4.4 kg for the 41 patients taking aripiprazole.
All the drugs significantly increased fat mass and waist circumference. In all, 10%–36% of patients, depending on which agent they were taking, gained enough weight to shift into overweight or obese status.
Lipid and metabolic abnormalities were not consistent across all four medications. Olanzapine and quetiapine significantly worsened total cholesterol, triglyceride, non-HDL cholesterol, and other lipid measures, while risperidone significantly raised triglycerides. Quetiapine and olanzapine raised the rates of hyperglycemia and metabolic syndrome.
Olanzapine in particular had the largest weight effects, “and also significantly worsened all glucose and lipid parameters, except HDL cholesterol, which is more related to physical activity,” the investigators said (JAMA 2009;302:1765–73).
In contrast, the control group showed no such changes, indicating that these alterations could not be attributed to the psychiatric disorder itself or to other aspects of treatment.
“In view of poor physical health outcomes and suboptimal metabolic monitoring in the severely mentally ill, the benefits of second-generation antipsychotic medication 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,” the authors said.
Vitals
Major Finding: More than half of the active treatment subjects gained more than 7% of total body weight after a median of 11 weeks.
Data Source: Cohort of 272 children/adolescents being treated with atypical antipsychotics.
Disclosures: Dr. Correll reported being a consultant or receiving honoraria from and serving on the speakers bureau of numerous pharmaceutical companies, including makers of some of the drugs studied. Dr. Varley and Dr. McClellan reported no disclosures.