Rationale and Comments

Research shows that use of two or more antipsychotic medications occurs in 4% to 35% of outpatients and 30% to 50% of inpatients. However, evidence for the efficacy and safety of using multiple antipsychotic medications is limited, and risk for drug interactions, noncompliance, and medication errors is increased. Generally, the use of two or more antipsychotic medications concurrently should be avoided except in cases of three failed trials of monotherapy, which included one failed trial of clozapine where possible, or where a second antipsychotic medication is added with a plan to cross-taper to monotherapy.

Sponsoring Organizations

• American Psychiatric Association

Sources

• American Psychiatric Association guidelines

Disciplines

• Psychiatric and Psychologic

References

• American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004 Feb;161(2 Suppl):1-56. Available from: http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1682213.
  
• Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45(9):789-96.
  
• McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, Swartz MS, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK, CATIE Investigators. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry. 2006;163(4):600-10.
  
• Maglione M, Ruelaz Maher A, Hu J, Wang Z, Shanman R, Shekelle PG, Roth B, Hilton L, Suttorp MJ, Ewing BA, Motala A, Perry T; Southern California Evidence-Based Practice Center. Off-label use of atypical antipsychotics: an update. Rockville, Md.: Agency for Healthcare Research and Quality; 2011 Sep 437 p. Report No.: HHSA290-2007-10062-1.
  
• Specifications Manual for Joint Commission National Quality Measures (v2013A1). Measure Set: Hospital Based Inpatient Psychiatric Services (HBIPS), Set Measure ID: HBIPS-4.
  
• Stahl SM, Grady MM. A critical review of atypical antipsychotic utilization: comparing monotherapy with polypharmacy and augmentation. Curr Med Chem. 2004;11(3):313-27.