Childhood-onset schizophrenia is rare, and children with this disorder often do not respond to standard treatment. Moreover, children with schizophrenia are thought to be more sensitive to the adverse effects of typical antipsychotic medications. Kumra and colleagues conducted a double-blind study to compare the efficacy and adverse effects of clozapine therapy with that of haloperidol therapy.
Patients less than 18 years of age were included in the study if they had no neurologic or medical illness, met criteria for schizophrenia as given in the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), had documented psychosis by age 12 and had unsuccessful trials of at least two antipsychotic medications. Eleven boys and 10 girls were randomly assigned to receive six weeks of therapy with either clozapine (starting at a dosage of 6.25 to 25 mg per day, increasing as needed to a maximum of 525 mg per day) or haloperidol (0.25 to 1.0 mg per day, increasing as needed up to 27 mg per day). Patients randomized to receive haloperidol also received prophylactic benztropine mesylate (maximum: 6 mg per day); the clozapine group received placebo in place of the benztropine. The study medications were started after a two-week taper of previous medications and a four-week washout period. Extensive laboratory testing, including magnetic resonance imaging and lumbar puncture, took place after physical examination. Behavior was assessed weekly, as were adverse effects.
Clozapine was found to be significantly more effective than haloperidol in decreasing both positive and negative symptoms of schizophrenia. Specifically, depression, social withdrawal and thought disturbances were markedly improved. Clozapine caused significantly more drowsiness and salivation than haloperidol, whereas haloperidol caused significantly more insomnia. In addition, clozapine caused five patients to have a drop in the neutrophil count to less than 1,500 per [mm.sup.3] (1.5 x [10.sup.9] per L), and caused two patients to have seizures, which necessitated their withdrawal from the study. Follow-up indicated that some patients showed benefit beginning at six to nine months after receiving clozapine therapy, with some of the study patients returning to less restrictive living environments.
The authors recommend consideration of clozapine for childhood-onset schizophrenia with the caveat that the patient be closely monitored for hematologic abnormalities and onset of seizures.
Kumra S, et al. Childhood-onset schizophrenia: a double-blind clozapine-haloperidol comparison. Arch Gen Psychiatry 1996;53:1090-7.
COPYRIGHT 1997 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group
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