American Psychiatric Association

View all recommendations from this society

Released September 20, 2013

Don’t routinely prescribe two or more antipsychotic medications concurrently.

Concurrent prescription of two or more antipsychotic medications is common, although the evidence for the efficacy and safety of this practice is limited. In addition, concurrent use of more than one antipsychotic medication may increase the potential for side effects, drug-drug interactions, and difficulties with adherence. There may be some circumstances when it is appropriate and beneficial to prescribe two or more antipsychotic medications concurrently, such as when changing from one medication to another or when an optimal dose of one antipsychotic medication is not sufficient to reduce symptoms of schizophrenia. However, even in the treatment of schizophrenia, before prescribing two or more antipsychotic medications concurrently, it is important to consider other strongly evidence-based options such as a trial of clozapine or adding an evidence-based psychotherapy.

These items are provided solely for informational purposes and are not intended as a substitute for consultation with a medical professional. Patients with any specific questions about the items on this list or their individual situation should consult their physician.

How The List Was Created

The American Psychiatric Association (APA) created a work group of members from the Council on Research and Quality Care (CRQC) to identify, refine and ascertain the degree of consensus for five proposed items. Two rounds of surveys were used to arrive at the final list: the first round narrowed the list from more than 20 potential items by inquiring about the extent of overuse, the impact on patients’ health, the associated costs of care and the level of evidence for each treatment or procedure; and the second gauged membership support for the top five and asked for suggested revisions and comments. The surveys targeted the CRQC; the Council on Geriatric Psychiatry; the Council on Children, Adolescents, and Their Families; and the Assembly, which is the APA’s governing body consisting of representative psychiatrists from around the country. After the work group incorporated feedback from the two large surveys, the APA’s Board of Trustees Executive Committee reviewed and unanimously approved the final list.

On April 22, 2015, APA revised item 3. Read more about these changes and rationale.

For APA disclosure and conflict of interest policy please visit


American Psychiatric Association. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. Washington DC: American Psychiatric Association, 2021.

Flanagan RJ, Lally J, Gee S, Lyon R, Every-Palmer S, Clozapine in the treatment of refractory schizophrenia: a practical guide for healthcare professionals, British Medical Bulletin, Volume 135, Issue 1, September 2020, Pages 73–89,

Foster A, King J. Antipsychotic Polypharmacy. Focus (Am Psychiatr Publ). 2020 Oct;18(4):375-385.

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.

Lähteenvuo M, Tiihonen J. Antipsychotic Polypharmacy for the Management of Schizophrenia: Evidence and Recommendations. Drugs. 2021 Jul;81(11):1273-1284.

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.