title: Infection and inflammation leading to clozapine toxicity and intensive care: a case series.
abstract: OBJECTIVE
  To describe 3 cases of clozapine toxicity associated with infectious and/or inflammatory processes.
  
  
  METHODS
  Three patients stable on clozapine therapy prior to a medical hospital admission developed clozapine toxicity. It was suspected that an acute infectious and/or inflammatory process in each patient was related to abrupt mental status changes, onset of sialorrhea, myoclonus, and/or need for ventilatory support. Investigations of altered mental status did not reveal alternative causes and presentations were not consistent with neuroleptic malignant syndrome, other acute neurologic complications, or psychiatric decompensation. All patients improved after clozapine dose reductions allowing for transfer from intensive care units. Using the Naranjo ADR Probability Scale for each case, a probable relation between clozapine toxicity and the infectious and/or inflammatory process was determined.
  
  
  CONCLUSIONS
  Clozapine toxicity may manifest with multiple symptoms, including sedation, sialorrhea, and hypotension. In addition to overdose and drug interactions; infection and/or inflammation may precipitate clozapine toxicity. This may be related to cytokine-mediated inhibition of cytochrome P450 1A2. The likelihood of toxicity via this mechanism has not been well characterized, thus careful monitoring is required for medically ill patients receiving clozapine. Clozapine is extensively bound to the acute phase reactant, α-1 acid glycoprotein, which may unpredictably protect against clinical toxicity. C-reactive protein has also been investigated to relate clozapine toxicity to infection and/or inflammation.
  
  
  CONCLUSIONS
  Clozapine toxicity developed in 3 patients admitted to a medical setting suspected to be related to infection and/or inflammation. Clinicians should be aware of this potential adverse drug event with clozapine.
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Leung
authors.forename: Sarah
authors.initials: S
authors.lastname: Nelson
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Takala
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Gören
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000150:complications*; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D003422:Critical Care; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: antipsychotics (atypical); psychiatry; psychotropics; schizophrenia; toxicity