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New But Not Improved

Marked weight gain is one drawback of newer drugs to treat schizophrenia in children

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When it comes to treating schizophrenia and schizoaffective disorders in children and adolescents, it seems newer is not always better.

New findings from the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) Study provide food for thought: youngsters treated with molindone (Moban), a first-generation antipsychotic, responded just as well to treatment as those taking one of two second-generation antipsychotics, olanzapine (Zyprexa) or risperidone (Risperdal). Both newer drugs, however, were associated with significant weight gain and alterations in metabolic profiles that included increases in levels of fasting cholesterol, LDL, insulin and liver transaminase.1

Extreme Weight Gain

Jon McClellan, MD, medical director of the Child Study and Treatment Center at Seattle Children's Hospital, and a co-author of the new study, who helped write the current guidelines for treating childhood schizophrenia. He recommends considering older medications for some children with schizophrenia.

"Some of the children in this study gained 15 pounds or more in 8 weeks," he said. "That's as much as adults gain in a year on these medications. Children are especially susceptible to these side effects, and this has broad implications across the board for the use of these agents to treat any disorder."

The TEOSS study affirmed findings from four child and adolescent psychiatric departments about the weight and BMI of youngsters treated with three drugs, including olanzapine and risperidone. "Olanzapine is associated with extreme long-term weight gain in children and adolescents that, in addition, is much higher than that expected in adults.risperidone [is] associated with a less marked weight gain in children and adolescents, but also much higher than that expected in adults."2

These findings question the nearly exclusive use of these second-generation drugs for children along the schizophrenia spectrum. The very significant weight gain, coupled with unfavorable metabolic changes, raise the specter of chronic diseases and have serious implications for the children's long-term health and well-being.

Evolving Evidence

Carole Hynes, MSN, RN-CS, serves as clinical coordinator of the Adolescent Day School at NorthShore University HealthSystem, Evanston, IL, a therapeutic school accredited by the Illinois State Board of Education and also part of the Department of Psychiatry. "We serve 25 students with severe psychiatric and emotional disorders who can't be educated in their local schools," she explained. "The students take a lot of psychotropic medications; most of them are on multiple medications to manage the emotional and behavioral components of their mental illness."

Hynes has been certified as a clinical specialist in mental health since 1985, back when the older antipsychotics were the drugs of choice for schizophrenia and other psychotic disorders. "Some of the side effects of those older drugs were truly frightening," she noted. "I've seen acute dystonic reactions that prevented the child from moving his head, as well as akathisia [sensation of inner restlessness that prevents the child from sitting still] that was very traumatizing to the teen." The TEOSS study did identify akathisia as a relatively common side effect of molindone.

As new drugs are developed and tested first in adults and then in children, clinicians need to keep abreast of advances. "I've watched the progression to the newer medications like.Risperdal, and we're still seeing new drugs every year," Hynes said. "The newer meds are very helpful, but they certainly have their side effects as well. I've seen some girls gain 30 pounds in 4 weeks, continuing on to gain 50-60 pounds. Sometimes we can change them to another medication, but sometimes not."

Early Intervention

Hynes emphasizes the need for further research into the link between antipsychotics and weight gain.

"What's interesting to me is the weight gain happens only in certain kids," she said. "An underweight boy may start on a new drug and we're hoping he'll gain weight, but he doesn't. Another student may gain steadily on the same drug; there's no rhyme or reason to who is susceptible to that side effect."

Hynes makes sure to weigh the children regularly. If they gain 10 pounds or so, she strongly recommends re-evaluating the use of a particular medication. "The physician has placed the student on that drug to treat significant presenting symptoms such as psychotic thinking or severe behavioral problems, and may not be focused on the significance of the weight gain," she said. "[But] for adolescent girls who are so self-conscious to begin with, weight gain can be very troublesome. I try to nip it in the bud before it gets up to 30 or 40 pounds."

Good Nutrition & Exercise

Michael A. Jenike, MD, professor of psychiatry at Harvard Medical School, director of the OCD Institute at McLean Hospital, Belmont, MA, and the OCD Clinic at Massachusetts General Hospital, recommends a healthy diet with a focus on lean proteins, fresh fruits and vegetables, whole grains, and heart-healthy mono-saturated fats like olive oil and canola oils to counteract the weight gain from newer anti-psychotics. He suggests eating smaller amounts of food at any given meal.

Jenike advocates a blend of anaerobic exercise such as walking, biking and jogging and resistance training such as weight-lifting and using resistance bands and tubes to improve energy levels and metabolism in children and teens with psychiatric disorders.

Hynes incorporates physical activity throughout the school day. "If the medication is sedating, the kids become a lot less active, which exacerbates the weight gain," she noted. "I'm a strong believer in the benefits of exercise for improving mood, as well as for preventing weight gain. We do a lot in our school's physical education class, going twice a week to a local facility for an hour of activity. We take walks during lunch time in the summer, and on Fridays we have a café session where many of the kids get up and dance."

Evaluating Medications

Sanjiv Kumra, MD, director of child and adolescent psychiatry at the University of Minnesota, Minneapolis, summarized the implications of the TEOSS findings. "It's a trial and error process to match people with the right medication," he said. "This says all treatments work, at least for some people, and have serious risks for others."

Hynes and her colleagues collaborate to try out different dosing options, perhaps dividing doses throughout the day instead of giving all the medication at bedtime. "That seems to be helpful in improving tolerance and behavioral control, and might help the weight issue as well," she said.

It's important to look at the financial burden of second-generation anti-psychotics when developing medication regimens. "We need to consider the cost for certain families, because these newer medications are very expensive," said Hynes. "In our life skills class at school, we discuss budget; one of the girls said her family spends $1,000 a month for her medications! In the right situation, if the child can tolerate and benefit from one of the older drugs, that's certainly something to consider."

Sandy Keefe is a frequent contributor to ADVANCE.


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