title: Optimizing clozapine treatment.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit for Psychiatric Research, Aalborg Psychiatric Hospital, Aarhus University Hospital, Denmark. jin@rn.dk
authors.forename: J
authors.initials: J
authors.lastname: Nielsen
authors.forename: P
authors.initials: P
authors.lastname: Damkier
authors.forename: H
authors.initials: H
authors.lastname: Lublin
authors.forename: D
authors.initials: D
authors.lastname: Taylor
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002121:Calcium Channel Blockers; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004565:Electroconvulsive Therapy; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D000077213:Lamotrigine; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome; D014227:Triazines
chemical_list: D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D014227:Triazines; D003024:Clozapine; D000077213:Lamotrigine