Older Antipsychotic Drugs as Effective as Newer Ones in Children with Schizophrenia

Nearly every child who receives an antipsychotic medicine is first prescribed one of the second-generation, or “atypical” drugs, such as olanzapine and risperidone. However, there has never been evidence that these drugs are more effective than the older, first-generation medications.

Nearly every child who receives an antipsychotic medicine is first prescribed one of the second-generation, or “atypical” drugs, such as olanzapine and risperidone. However, there has never been evidence that these drugs are more effective than the older, first-generation medications.

Seattle Children’s Research Institute participated in a four-site study resulting in new findings suggesting that molindone, a first-generation drug, is just as effective as the newer medications and may be used as a first line of therapy in some children with schizophrenia or schizoaffective disorder. Jon McClellan, MD, child psychiatrist at Children’s, is one of the lead authors.

“Our safety findings regarding these second-generation antipsychotic medications have broad public health implications. These agents are being prescribed widely for many children with many different conditions,” said McClellan. “We’ve seen several-fold increases in the use of these medications during the last eight years. These drugs are far more widely used in the United States than anywhere else in the world.”

The second-generation antipsychotic medications are prescribed for a variety of psychiatric problems in children, including mood, behavior and aggression disorders, autism, schizophrenia and schizoaffective disorder.

This study is the largest head-to-head pediatric trial comparing the newer second-generation drugs to an older medication. The study is published in the September 15, 2008 edition of the American Journal of Psychiatry.

“People thought the second-generation drugs were superior because they had no side effects. We found that molindone works as well as newer drugs, and in some cases it’s safer,” said Lin Sikich, MD, Associate Professor in the Department of Psychiatry at University of North Carolina at Chapel Hill (UNC) and lead author of the multi-site study, titled the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study (TEOSS).

Between 2002 and 2006 the study randomly assigned 119 people aged 8 to 19 years to receive molindone, olanzapine or risperidone over an eight-week period. The study was conducted at four sites: UNC, Seattle Children’s Research Institute, McLean Hospital and Cambridge Health Alliance at Harvard Medical School, and Case Western Reserve University.

In the TEOSS study, the reduction in psychotic symptoms was similar across the three medications. However, researchers found the drugs caused very different types of side effects. Both olanzapine and risperidone were associated with significant weight gain and put young patients at risk of developing heart disease and diabetes. In fact, the National Institute of Mental Health, which sponsored the study, halted subject recruitment into the olanzapine arm of the study because of the weight gain problem and the resulting increase in cholesterol and glucose levels. As a result, researchers suggest that olanzapine should not be a first-line therapy in youth.

There were more reported cases of restlessness with molindone treatment than with either of the two newer treatments. Participants treated with molindone were also required to receive another drug, benztropine, to decrease muscle cramps and stiffness.

The study also addresses the benefits of proper diagnosis and the need for more effective medications to treat psychotic illnesses. A delay in diagnosis is a common problem with many children who develop early onset schizophrenia or schizoaffective disorder, and the diseases are usually more severe when they begin in childhood, researchers said.

About Seattle Children’s

Seattle Children’s Hospital, Foundation and Research Institute together deliver superior patient care, advance new discoveries and treatments through pediatric research, and raise funds to create better futures for patients. Consistently ranked as one of the top 10 children’s hospitals in the country by U.S. News & World Report, Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental needs of children from infancy through young adulthood. Through the collaboration of physicians in nearly 60 pediatric subspecialties, Seattle Children’s Hospital provides inpatient, outpatient, diagnostic, surgical, rehabilitative, behavioral, and emergency and outreach services to families from around the world.

Located in downtown Seattle’s biotech corridor, Seattle Children’s Research Institute is pushing the boundaries of medical research to find cures for pediatric diseases and improve outcomes for children all over the world. Internationally recognized investigators and staff at the research institute are advancing new discoveries in cancer, genetics, immunology, pathology, infectious disease, injury prevention, bioethics and much more.

Seattle Children’s Hospital and Research Foundation and Seattle Children’s Hospital Guild Association work together to gather community support and raise funds for uncompensated care, clinical care and research. The foundation receives nearly 80,000 gifts each year, from lemonade stand proceeds to corporate sponsorships. Seattle Children’s Hospital Guild Association is the largest all-volunteer fundraising network for any hospital in the country, serving as the umbrella organization for 450 groups of people who turn an activity they love into a fundraiser. Support from the foundation and guild association makes it possible for Seattle Children’s care and research teams to improve the health and well-being of all kids.

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