Weight Gain in Kids on Antipsychotic Medicines

It has been known for several years that antipsychotic medications can cause weight gain in adults and increase the risk for serious metabolic disorders. Scientists at The Zucker Hillside Hospital and The Feinstein Institute for Medical Research embarked on a large study following children and adolescents who have been prescribed antipsychotic medicines for the first time and examining the impact they had on weight gain and metabolic changes. Indeed, researchers identified a worrisome degree of weight gain and caution their colleagues to take these changes seriously. Weight gain and changes in blood glucose and lipid metabolism can be precursors of diabetes, hypertension, metabolic syndrome, stroke and heart attack. The children tested were between 4-19 years old.

    "The data sheds further light on the frequency and severity of weight gain associated with these newer antipsychotics,” said Christoph U. Correll, MD, medical director of the Recognition and Prevention (RAP) program at the Zucker Hillside Hospital and a scientist in the Feinstein Institute’s Center for Psychiatric Neuroscience. “Our findings suggest increased caution in prescribing them to pediatric patients.”

    The scientists studied 272 young people who had been prescribed antipsychotic medicines for a range of serious behavioral, mood and psychosis-related problems. The patients were prescribed one of a number of second-generation antipsychotics and followed over the first 12 weeks to assess changes in weight, blood glucose and lipids. At around 11 weeks, the young patients had gained an average of 19 pounds on the antipsychotic, olanzapine; 13.5 pounds on quetiapine; 11.9 pounds on risperidone; and 9.9 pounds on aripiprazole. By comparison, 15 patients who refused participation in the study or were not compliant with taking the antipsychotics were used as a control group and their weight gain during the same study period was less than a half-pound.

    The findings were published this week in the Journal of the American Medical Association (JAMA).

    The scientists also identified substantial changes in triglycerides and cholesterol, and found that the weight gain alone did not seem to explain entirely the adverse metabolic effects that varied significantly across the individual medications. All of the findings, Dr. Correll said, “should be considered when choosing antipsychotics.” SATIETY (Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth) is the largest cohort study of atypical antipsychotic treatment in children and adolescents treated with antipsychotics. It is also the largest study of its kind in children or adults who received antipsychotic treatment for the first time in their life. This is a key study feature because prior treatment can obscure the true cardiometabolic effects of medications. In the SATIETY study, the antipsychotic-naïve youths suffered from a range of problems, including psychosis (30.1 percent,) mood disorders (47.8 percent) and aggressive behavior (22.1 percent).  Researchers followed these patients to understand if weight and metabolic changes are due to the new onset of a psychiatric illness or related hospital admission, or whether the observed changes are effects of the antipsychotic treatment.

    The scientists found that the worsening of metabolic parameters differed between the antipsychotic medications groups, despite the shared, large and significant changes in body weight parameters, including waist circumference. Olanzapine, which was also associated with the largest effects on body weight, was associated with the greatest and most widespread worsening of lipid as well as glucose parameters. Quetiapine and risperidone were associated with varying degrees of lipid abnormalities only, which were more pronounced with quetiapine. By contrast, aripiprazole was not associated with any significant worsening in glucose or lipid parameters, which was also the case in the comparison subjects.  “These findings provide further evidence for an additional, weight independent mechanism for glucose and lipid abnormalities with olanzapine that does not seem to be shared by the other antipsychotics that were studied,” said Dr. Correll.

    Antipsychotic medication use in young people has grown substantially in recent years and this study calls into question the effects of this upward trend.  “Abnormal childhood weight and metabolic status adversely affect adult cardiovascular outcomes via continuation of these risk factors or independent or accelerated mechanisms,” the scientists wrote. “Our results, together with data from first-episode studies, suggest that guidelines for antipsychotic medication exposure for vulnerable pediatric and adolescent patients naive to antipsychotic medication should consider more frequent (e.g., biannual) cardiometabolic monitoring after the first three months of treatment. Finally, in view of poor physical health outcomes and suboptimal metabolic monitoring in the severely mentally ill, 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 accompanying editorial, Christopher K. Varley, M.D., and Jon McClellan, M.D., of Seattle Children’s Hospital, said that while “these medications can be lifesaving for youth with serious psychiatric illnesses such as schizophrenia, classically defined bipolar disorder, or severe aggression associated with autism,” and “given the risk for weight gain and long-term risk for cardiovascular and metabolic problems, the widespread and increasing use of atypical antipsychotic medications in children and adolescents should be reconsidered.”

    This study was, in part, supported by the Feinstein's General Clinical Research Center.

About The Feinstein Institute for Medical Research

Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in cancer, leukemia, lymphoma, Parkinson's disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, neuroimmunology, and medicinal chemistry.  Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient, annually enrolling some 10,000 subjects into clinical research programs. 

About The Zucker Hillside Hospital

The Zucker Hillside Hospital is home to many of the nation’s experts on severe mental illness. In addition to treating patients in and out of the hospital, psychiatric research has been ongoing for decades and includes landmark studies on the treatment and course of first-episode psychotic patients. Genetics also plays a critical role in severe mental illness and scientists at the Zucker Hillside Hospital have identified several important risk genes. John Kane, MD, chair of psychiatry at Zucker Hillside, and his team of scientists recently received a $26 million federal grant to train psychiatric staff across the country to deliver state-of-the-art treatments for patients with a first episode of schizophrenia and to test whether it works to delay or alter the disabling course of the illness.