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Clozapine Better Than "High-Dose" Olanzapine for the Treatment of Adolescents With Schizophrenia

NEW YORK -- March 24, 2008 -- The results of a 12-week, double-blind, randomised study published in the March issue of Biological Psychiatry suggest that clozapine is more effective than "high-dose" olanzapine for the treatment of children and adolescents with schizophrenia who do not respond to standard, first-line antipsychotic treatment.

There is a wealth of scientific literature available on the treatment of adults with schizophrenia. However, there is a paucity of data to guide the treatment of children and adolescents with schizophrenia.

"Although the US Food and Drug Administration has recently approved the use of aripiprazole and risperidone for adolescents with schizophrenia, few controlled data are available to help guide clinicians regarding the management of children and adolescents with schizophrenia who fail to respond to these standard 'first-line' antipsychotic treatments," according to Dr. Sanjiv Kumra, University of Minnesota, Minneapolis, Minnesota, one of the authors of the study.

Study participants (N = 39) were children aged 10 to 18 years who failed to respond to 2 or more antipsychotic treatments. After initial assessment, the patients received treatment with either clozapine or "high-dose" olanzapine and were monitored for improvement of their symptoms.

The researchers discovered that clozapine was nearly twice as likely to produce a treatment response compared with olanzapine. Positive symptoms (eg, psychosis) and negative symptoms (eg, blunted emotional response, reduced motivation) also responded better to clozapine.

John H. Krystal, MD, Editor, Biological Psychiatry, Yale University School of Medicine, New Haven, Connecticut, and VA Connecticut Healthcare System, West Haven, Connecticut, commented that "olanzapine is among the most effective antipsychotic medications, so the distinctive effectiveness of clozapine in this study could be very important."

Both medications produced significant weight gain and associated metabolic abnormalities in the study participants, and Dr. Krystal noted that clozapine does have important adverse effects that have discouraged its prescription to children.

Most of the study population had a history of multiple hospitalizations, extreme violence, suicidality, and trauma before enrollment in the study. "Without appropriate intervention, it is likely that many would have ended up in long-term care institutions; psychiatric prison settings; and/or experienced early death from drug use, violence, or suicide," noted Dr. Kumra. "So, [these] preliminary data are hopeful, indicating that proper and effective treatment may be available for these adolescents, although there are also concerns."

Although clozapine is often considered as a treatment of last resort because of its associated risk of agranulocytosis, the authors noted that the reduction in observed symptoms makes it apparent that clozapine may help in the care of youth with treatment-refractory schizophrenia.

"The long-term risks of medications, such as clozapine and olanzapine," concluded Dr. Krystal, "will need to be weighed against their potential benefits. Thus, additional research will be needed to follow up on this exciting but very preliminary finding."

SOURCE: Biological Psychiatry, March 1, 2008

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