title: Factors affecting interindividual differences in clozapine response: a review and case report.
abstract: 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.
authors: Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy. bersani.fs@tiscali.it
authors: Francesco Saverio
authors: FS
authors: Bersani
authors: Enrico
authors: E
authors: Capra
authors: Amedeo
authors: A
authors: Minichino
authors: Rossella
authors: R
authors: Pannese
authors: Nicoletta
authors: N
authors: Girardi
authors: Isabella
authors: I
authors: Marini
authors: Roberto
authors: R
authors: Delle Chiaie
authors: Massimo
authors: M
authors: Biondi
mesh_terms: D003024:Clozapine / Q000627:therapeutic use*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D006801:Humans; D007206:Individuality; D008297:Male; D012559:Schizophrenia / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D003024:Clozapine