The trial investigators concluded that when clinicians switch drug regimens for stable patients with chronic schizophrenia from polypharmacy to monotherapy, they need to proceed cautiously, monitoring them for symptoms and side effects for at least 12 months, and adjusting the AP dose accordingly.1 

Two previous randomized clinical trials involving a switch from AP polypharmacy to monotherapy differed in their focus and their findings.6,7 H. Hori and colleagues looked at cognitive and social function in patients with schizophrenia who switched from polypharmacy to monotherapy. The change was implemented by gradually reducing the dose level of one of the two antipsychotics to zero. The study, which included 39 patients with schizophrenia, found that switching to monotherapy resulted in significant improvement in attention (P=.02), daily living (P=.038), and work skills (P=.04).6  

An earlier randomized trial, by S. M. Essock and colleagues, found that adult outpatients with schizophrenia who switched to monotherapy were more likely and quicker to discontinue treatment than those who remained on polypharmacy. Switching was successful in 2/3 of the patients, however, and psychiatric symptom control and hospitalization rate did not differ between the switch and stay groups. In addition, those who switched to monotherapy tended to lose weight, while those on polypharmacy tended to gain. The trial included 127 participants from 19 sites and lasted 6 months, with a 6-month follow up period.7    

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As several studies have noted, additional research is needed to addresses the issues surrounding AP polypharmacy, as is further study of the effectiveness and safety of switching from AP polypharmacy to monotherapy.


1. Constantine RJ, Andel R, McPherson M, Tandon R. The risks and benefits of switching patients with schizophrenia or schizoaffective disorder from two to one antipsychotic medication: a randomized controlled trial. Schizophr Res. 2015 Aug; 166(1-2):194-200. doi: 10.1016/j.schres.2015.05.038. Epub 2015 June 30.

2. Choban PS, Mittal R, Jayed A. Antipsychotic mediation and QT prolongation. Pak J Med Sci. 2015 Sep-Oct;31(5):1269-71. doi: 10.12669/pjms.315.8998

3. Barbui C, Bighelli I, Carra G, et al. Antipsychotic dose mediates the association between polypharmacy and corrected QT interval. PLoS One. 2016 Feb 3:11(2):e0148212. doi: 10.1371/journal.pone.0148212. eCollection 2016.

4. Tani H, Uchida H, Suzuki T, Fujii Y, Mimura M. Interventions to reduce antipsychotic polypharmacy: a systematic review. Schizophr Res. 2013 Jan;143(1):215-20. doi: 10.1016/j.schrs.2013.10.2015. Epub 2012 Nov 14.

5. Sernyak MJ, Rosenheck R. Clinicians’ reasons for antipsychotic coprescribing. J Clin Psychiatry. 2004 Dec;65(12):1597-600.

6. Hori H, Yoshimura R, Katsuki A, et al. Switching to antipsychotic monotherapy can improve attention and processing speed, and social activity in chromic schizophrenia patients. J Pyschiatr Res. 2013 Dec;47(12):1843-8. doi: 10.1016/j.jpsychires.2013.08.024. Epub 2013 Sep 7.

7. Essock SM, Schooler NR, Stroup TS, et al. Effectiveness of switching from antipsychotic polypharmacy to monotherapy. Am J Psychiatry. 2011 Jul;168(7):702-8. doi:10.1176/appi.ajp.2011.10060809. Epub 2011 May 2.