An Open Trial of Clozapine in Thirty-Six Adolescents with Schizophrenia

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Abstract
A retrospective study of 36 adolescents with schizophrenia treated in open clinical trials with clozapine, following treatment failure on at least 2 conventional neuroleptic medications, demonstrated that 75% (27 of 36) showed notable symptomatic improvement. Four adolescents (11%) showed an essentially complete remission of symptoms. The majority of patients became able to participate in a comprehensive rehabilitation program. Positive symptoms of schizophrenia were more responsive to clozapine than were negative symptoms, but certain negative symptoms showed some modest improvement. Three patients (8%) did not respond to clozapine, and six patients (17%) required discontinuation of treatment due to adverse effects, so a total of 25% of these adolescents did not respond to clozapine treatment. Leukopenia (without agranulocytosis) was observed in 8% (three patients), which is consistent with findings in adults. Unexpectedly, some extrapyramidal symptoms were observed. Mean dose was 330 mg daily (range, 50-800 mg daily), and the mean duration of these open clinical trials was 154 days. In prior treatments with typical neuroleptic agents, these 36 adolescents with schizophrenia had shown nonresponse, worsening of symptoms, or significant adverse effects. Although controlled research protocols are needed to evaluate this medication in adolescents, these clinical data suggest that clozapine may enrich the range of possible therapeutic interventions for adolescents with schizophrenia that is resistant to typical neuroleptic treatment. However, the safety of this treatment in adolescents requires considerably greater study, especially in view of the extrapyramidal side effects observed in some adolescents.

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