Youngsters and Antipsychotics: Old vs. New

Contrary to popular belief, schizophrenia is not split personality. It is a serious brain disorder—the most chronic and disabling of the major mental illnesses—that distorts the way a person acts, thinks, expresses emotions, perceives reality and relates to others. No one knows exactly what causes schizophrenia, but genetic makeup and brain chemistry may play a role. There is no cure for schizophrenia but medicines can relieve many of the symptoms. A new class of drugs called atypical antipsychotics was developed in the 1990s and has become the drugs of choice for treating children and teenagers. However, a new government study has found that these medicines are no more effective than older, less expensive drugs and are more likely to cause some harmful side effects.
For the study, dubbed "The Treatment of Early Onset Schizophrenia Study" (TEOSS), researchers, led by Dr. Linmarie Sikich of the University of North Carolina, recruited 119 young people ages 8 to 19 who suffer from psychotic symptoms. They were given either Zyprexa from Eli Lilly, Risperdal from Johnson and Johnson, or an older drug called molindone, or Moban, plus benztropine, a medication often used to reduce side effects like uncontrolled shaking or tremors that can be associated with molindone. Neither the patients nor the doctors treating them knew which drug was being taken. The study was monitored throughout by a National Institute of Mental Health (NIMH) oversight board to ensure the children’s safety.
After eight weeks of treatment, 50 percent of those taking molindone showed improvement in their symptoms, compared to 46 percent who were taking Risperdal and 34 percent of those taking Zyprexa. Statistically, there was no significant difference among the improvements seen in the three groups. However, half of the children in the study stopped taking their drug within the two months, either because it had no effect or was causing serious side effects, including rapid weight gain. The Risperdal group gained an average of nine pounds, and the Zyprexa group gained an average of 13 pounds before the oversight board ordered they be taken off the drug. Levels of a hormone, prolactin, also rose among patients taking Risperdal, which could trigger early menstruation in girls and cause growth of breast tissue in boys.
Both the Risperdal group and the Zyprexa group also showed changes in cholesterol and insulin levels, which are known risk factors for diabetes, where those taking molindone gained less than one pound, on average, and showed little metabolic change. They did, however, have more akathisia—a movement disorder involving restlessness and need to fidget. “All three of these drugs have different side effect profiles, but the newer drugs are much more likely to cause weigh gain,” said Dr. Sikich.
Dr. Sikich points out that almost all children and adolescents now treated for schizophrenia begin treatment on the newer, atypical drugs. Prescription rates for these newer drugs have increased more than fivefold for children over the past 12 years. “Atypical antipsychotics are commonly used to treat kids with EOSS, but these results question the wisdom of that approach,” she said. “They also remind us that we need to develop safer, more effective medications to treat these children, given the limited effectiveness of both the atypical and the conventional medications.”
Study coauthor Jeffery Lieberman, M.D., of Columbia University Medical Center, noted that the TEOSS results are the first documented evidence of how newer antipsychotics compare to older ones when treating children and adolescents with schizophrenia. “Doctors need to educate families about the potentially serious side effects these drugs can have so that strategies can be put into place to address them,” he noted. The TEOSS results are similar to those found in the NIMH-funded Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), which found the newer antipsychotics no more effective than older ones in treating adults with schizophrenia.
Representatives for Eli Lilly and Johnson and Johnson told the Times that their drugs weren’t approved to treat schizophrenia in children and that there was a need for new therapies, given the small number of options for kids. Eli Lilly spokesman, Jamaison Schuler, pointed out that the new study had not lasted long enough to pick up well established, long-term side effects associated with the older drugs, which can include rigidity, persistent muscle spasms, tremors, and restlessness.Of the estimated 3 million Americans suffering from schizophrenia, about 1 million are children and teenagers. People with schizophrenia often have problems functioning in society and in relationships. In adolescents, the first signs can include a change in friends, a drop in grades, sleep problems, and irritability. But because many normal adolescents exhibit these behaviors as well, it can be difficult for doctors to make a diagnosis at this stage. “Schizophrenia and schizophrenia-related disorders are rare in childhood. But when they do occur, those afflicted generally have more severe symptoms and a worse prognosis than those who develop the disorder in adulthood,” said NIMH Director Thomas R. Insel, M.D. “The newer atypical antipsychotics are often used to treat these children, but until now, it has been unclear how effective and safe they really are in children. The side effects of the newer medications should be factored into making treatment decisions.”
The study was published online September 15, 2008, in the American Journal of Psychiatry.