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        Clozapine Monitoring Recommended In Schizophrenia Maintenance Therapy

        A DGReview of :"Therapeutic drug monitoring of clozapine and relapse--a retrospective study of routine clinical data."
        International Journal of Clinical Pharmacology and Therapeutics

        02/17/2003
        By David Loshak


        Therapeutic drug monitoring of clozapine, an atypical anti-psychotic, is recommended during maintenance treatment of patients with schizophrenia and schizo-affective disorders.

        Serum levels of the drug below 50 ng/ml might be related to relapses during maintenance, however, irrespective of concurrent psychotropic drugs. As well, levels below 250 ng/ml are associated with relapse in patients not taking any concurrent psychotropic drugs, say researchers at University Hospital, Magdeburg, Germany.

        The risk of relapse is low for serum levels of clozapine above 250 ng/ml whatever concurrent psychotropic drugs are being taken, although the risk of intoxication rises with serum levels above 750 ng/ml, they also report.

        The researchers noted that clinical studies had indicated a therapeutic window for clozapine serum levels in patients receiving acute treatment after failing to respond to treatment with typical anti-psychotics. But, although clozapine was often used as maintenance therapy, there were few data about its relationship with relapse prevention in that setting. These researchers conducted a retrospective study of routine therapeutic drug monitoring data to investigate this.

        Samples from patients recently admitted to an acute treatment ward were regarded as associated with relapse. Samples which could then be attributed to an intoxication were identified.

        The researchers recorded clozapine dose and serum level, age, sex, smoking habits, concurrent drugs and psychiatric diagnosis. Data on samples from each patient were summarised according to a typical clinical situation.

        After excluding patients receiving acute treatment, the researchers identified 65 relevant clinical situations: 20 poor outcomes (12 relapses, 8 intoxications) and 45 with good maintenance outcomes.

        Samples involving relapse had serum levels of 198 ± 211 ng/ml. Intoxications had serum levels of 1,969 ± 705 ng/ml. Patients with good outcomes had serum levels of 384 ± 255 ng/ml.

        Serum levels of clozapine were increased in women, old patients and non-smokers.
        International Journal of Clinical Pharmacology and Therapeutics 2003; 41:1:3-13. "Therapeutic drug monitoring of clozapine and relapse--a retrospective study of routine clinical data."

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