Choosing antipsychotics for children with schizophrenia: Evidence plus experience
Seeking efficacy while managing adverse effects in early-onset psychosis
“A patient I’ve seen for a number of years had been diagnosed in the pervasive developmental disorder spectrum, but she was quite atypical. Her perseverative thinking focused on a fantasy world, and she was so preoccupied that it was very difficult to pull her out of it. Now at age 12, she has a full-blown psychotic disorder, and the fantasy world is enveloping her. She hears people talking to her all day long.”
Jean A. Frazier, MD, who treats this patient and other children with psychotic disorders, was 1 of 4 principal investigators in the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) study, a randomized, double-blind, multisite trial funded by the National Institute of Mental Health. The study, published in November 2008,1 compared the efficacy and tolerability of 3 antipsychotics—olanzapine, risperidone, and molindone—in pediatric patients with schizophrenia or schizoaffective disorder (Box 1).
Dr. Frazier discusses the unexpected findings of the TEOSS trial with Current Psychiatry Section Editor Robert A. Kowatch, MD, PhD. Based on the trial findings and her experience, she tells how she makes decisions when prescribing antipsychotics for children and adolescents with schizophrenia and related disorders.
DR. KOWATCH: The TEOSS trial found no significant differences in efficacy between molindone and the atypical antipsychotics (olanzapine and risperidone) included in the study. You’ve prescribed both typical and atypical antipsychotics in research and in your clinical practice. Do you believe there’s any difference between the 2 classes?
DR. FRAZIER: There are some differences. For example, treatment-refractory patients, especially young children, sometimes need more D2 blockade than some atypical antipsychotics provide. I’ve seen more extra pyramidal side effects with the typical antipsychotics than the atypicals, although it’s not uncommon to see some akathisia with aripiprazole or some dystonia and dyskinesia with risperidone.
DR. KOWATCH: What are the benefits and risks of using antipsychotics in young children?
DR. FRAZIER: The benefit is that antipsychotics can decrease children’s suffering and get them more centered in reality so they can enjoy their friends and progress in school. And when that happens, it’s wonderful. What are the risks? With the atypicals my greatest concern is weight gain, and with the typical agents it’s tardive dyskinesia.
DR. KOWATCH: Have you changed the way you prescribe antipsychotics as a result of the TEOSS study?
DR. FRAZIER: Actually, I have. Clinicians have to be very careful about selecting psychotropic agents that can worsen pediatric-onset obesity. Olanzapine is an effective agent for targeting psychosis and mood symptoms, but the weight gain associated with it is a concern. I do not prescribe olanzapine as much as I have in the past, although I keep it in my armamentarium and tend to reserve it for third- or fourth-line therapy.
I have found molindone to be quite effective in children with schizophrenia or schizoaffective disorder, especially in those who have gained a lot of weight on atypical antipsychotics. They usually lose weight on molindone.
DR. KOWATCH: Do you think the TEOSS study had adequate power to demonstrate differences among molindone, olanzapine, and risperidone?
DR. FRAZIER: We enrolled 119 patients—which is large for a study such as this—but we did not reach our target of 168 patients, which might have increased our power to detect differences. Among the children we did enroll, the 3 antipsychotics showed no difference in efficacy, but the meaningful finding of this study to me was the side effect profile of these agents.
DR. KOWATCH: You mean weight gain with olanzapine and extrapyramidal symptoms with molindone?
DR. FRAZIER: Yes.
Managing side effects
DR. KOWATCH: How do you manage antipsychotic side effects?
DR. FRAZIER: For any of the antipsychotics’ side effects, you have to decide whether to continue the agent or switch to another anti psychotic. For example, I’ve had a number of children—many with significant weight problems—whose psychotic symptoms have responded only to risperidone. So we put them back on risperidone, and the decision then becomes what can we do to help with the weight gain while continuing that agent.
For weight gain, I think the best intervention is diet, exercise, and drinking a lot of water, but that can be effective only if you engage the patient’s entire family in the intervention as well. Short of that, a number of pharmacologic interventions have been studied, although not specifically in children.
