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OBJECTIVE: Clozapine is the most powerful new‐generation antipsychotic. Although this drug leads to great therapeutic benefits, two types of undesirable conditions frequently occur with its use: side effects and resistance to treatment. Therapeutic drug monitoring of clozapine would be very useful to avoid both these situations. The necessity of monitoring the therapy is the result of a wide interindividual variability in the metabolism of clozapine. In this review, we highlight all the conditions underlying this variability, analyzing them one by one. METHODS: Relevant literature was identified through a search of MEDLINE and PubMed. In addition, the case of a treatment‐resistant patient with accelerated metabolism of clozapine is reported as representative of utility of therapeutic drug monitoring in terms of clozapine dose adjustment. RESULTS: Genetic polymorphisms of cytochrome P450 enzymes and of neurotransmitter receptors; drug interactions; interactions of clozapine with other substances such as food and drink; smoking; and nonmodifiable variables such as age, ethnicity, and gender have been examined in relation to the existing scientific literature. The laboratory techniques that clinicians could use to identify these variables and adequate therapies are also reviewed.

Original publication




Journal article


Hum Psychopharmacol

Publication Date





177 - 187


Clozapine, Cytochrome P-450 CYP1A2, Humans, Individuality, Male, Schizophrenia, Treatment Outcome, Young Adult