Optimizing clozapine treatment

Acta Psychiatr Scand. 2011 Jun;123(6):411-22. doi: 10.1111/j.1600-0447.2011.01710.x. Epub 2011 Apr 28.


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.

Method: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Calcium Channel Blockers
  • Central Nervous System Diseases / chemically induced
  • Central Nervous System Diseases / prevention & control
  • Clozapine / adverse effects
  • Clozapine / therapeutic use*
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Monitoring
  • Drug Therapy, Combination
  • Electroconvulsive Therapy
  • Heart Diseases / chemically induced
  • Heart Diseases / prevention & control
  • Humans
  • Lamotrigine
  • Schizophrenia / drug therapy*
  • Treatment Outcome
  • Triazines


  • Antipsychotic Agents
  • Calcium Channel Blockers
  • Triazines
  • Clozapine
  • Lamotrigine