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Optimizing clozapine treatment


Jimmi Nielsen, M.D., Unit for Psychiatric Research, Aalborg Psychiatric Hospital, Aarhus University Hospital, Mølleparkvej 10, PO Box 210, DK-9100 Aalborg, Denmark.


Nielsen J, Damkier P, Lublin H, Taylor D. Optimizing clozapine treatment.

Objective:  Clozapine treatment remains the gold standard for treatment-resistant schizophrenia, but treatment with clozapine is associated with several side-effects that complicate the use of the drug. This clinical overview aims to provide psychiatrists with knowledge about how to optimize clozapine treatment. Relevant strategies for reducing side-effects and increasing the likelihood of response are discussed.

Method:  Studies of clozapine available in MEDLINE were reviewed.

Results:  A slow up-titration of clozapine is recommended in order to reach the optimal dosage of clozapine and diminish the risk of dose-dependent side-effects. Particularly, in case of partial response or non-response, the use of therapeutic drug monitoring of clozapine is recommended. Plasma levels above the therapeutic threshold of 350–420 ng/ml are necessary to determine non-response to clozapine. To ease the burden of dose-dependent side-effects, dose reduction of clozapine should be tried and combination with another antipsychotic drug may facilitate further dose reduction. For most side-effects, counteracting medication exists. Augmentation with lamotrigine, antipsychotics, or electroconvulsive therapy may be beneficial in case of partial response to clozapine.

Conclusion:  Treatment with clozapine should be optimized in order to increase the rate of response and to minimize side-effects, thus diminishing the risk of discontinuation and psychotic relapse.