title: Clozapine's critical role in treatment resistant schizophrenia: ensuring both safety and use.
abstract: BACKGROUND
  Clozapine was first introduced as an antipsychotic in the 1970's but a cluster of deaths, later linked to the drug's risk of agranulocytosis, led to its withdrawal in most countries. However, work in the 1980's established its unique efficacy in treatment resistant schizophrenia (TRS), which constitutes as many as 30% of those with the illness. Clozapine was reintroduced with this indication shortly thereafter, but because of this risk its use requires routine hematologic monitoring.
  
  
  METHODS
  An update is provided regarding clozapine's risk of neutropenia, agranulocytosis, and associated mortality. In addition, updates are provided on other side effects, specifically myocarditis and bowel obstruction, as evidence suggests these are more common than agranulocytosis and associated with higher mortality rates.
  
  
  CONCLUSIONS
  Clozapine remains the only treatment indicated in TRS, but it is dramatically underutilized. Clearly there are serious side effects associated with its use, and while the focus has historically been on hematologic concerns, we highlight other side effects that also demand systematic monitoring. Because it is the only effective treatment option we have for TRS, though, efforts must be implemented that ensure its use in this population while maximizing safety.
authors.affiliation: a Department of Psychiatry , University of Toronto , Toronto , ON , Canada.|b Institute of Medical Science , University of Toronto , Toronto , ON , Canada.|c Centre for Addiction and Mental Health (CAMH) , Toronto , ON , Canada.
authors.forename: G
authors.initials: G
authors.lastname: Remington
authors.affiliation: d Department of General Psychiatry 1 , Institute of Mental Health , Singapore , Singapore.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: a Department of Psychiatry , University of Toronto , Toronto , ON , Canada.|b Institute of Medical Science , University of Toronto , Toronto , ON , Canada.|c Centre for Addiction and Mental Health (CAMH) , Toronto , ON , Canada.
authors.forename: O
authors.initials: O
authors.lastname: Agid
authors.affiliation: a Department of Psychiatry , University of Toronto , Toronto , ON , Canada.|c Centre for Addiction and Mental Health (CAMH) , Toronto , ON , Canada.|e Department of Neuropsychiatry , Keio University School of Medicine , Tokyo , Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: a Department of Psychiatry , University of Toronto , Toronto , ON , Canada.|b Institute of Medical Science , University of Toronto , Toronto , ON , Canada.|c Centre for Addiction and Mental Health (CAMH) , Toronto , ON , Canada.
authors.forename: G
authors.initials: G
authors.lastname: Foussias
authors.affiliation: a Department of Psychiatry , University of Toronto , Toronto , ON , Canada.|b Institute of Medical Science , University of Toronto , Toronto , ON , Canada.|c Centre for Addiction and Mental Health (CAMH) , Toronto , ON , Canada.
authors.forename: M
authors.initials: M
authors.lastname: Hahn
authors.affiliation: a Department of Psychiatry , University of Toronto , Toronto , ON , Canada.|b Institute of Medical Science , University of Toronto , Toronto , ON , Canada.|c Centre for Addiction and Mental Health (CAMH) , Toronto , ON , Canada.
authors.forename: G
authors.initials: G
authors.lastname: Fervaha
authors.affiliation: c Centre for Addiction and Mental Health (CAMH) , Toronto , ON , Canada.
authors.forename: L
authors.initials: L
authors.lastname: Burton
authors.affiliation: c Centre for Addiction and Mental Health (CAMH) , Toronto , ON , Canada.
authors.forename: V
authors.initials: V
authors.lastname: Powell
mesh_terms: D000380:Agranulocytosis / Q000139:chemically induced; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D004351:Drug Resistance; D006801:Humans; D009503:Neutropenia / Q000139:chemically induced; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Clozapine; agranulocytosis; bowel obstruction; myocarditis; neutropenia; side effects; treatment resistant schizophrenia