Exploring hidden issues in the use of antipsychotic polypharmacy in the treatment of schizophrenia
Chi-Un Pae 1, 2*, Changsu Han 3, Won-Myong Bahk 1, Soo-Jung Lee 1, Ashwin Patkar 4, Prakash Masand 5
1Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea, 2Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea, 3Department of Psychiatry, Korea University, College of Medicine, Seoul, Republic of Korea, 4Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA, 5Global Medical Education, New York, NY, USA
Received: December 2, 2020; Revised: January 13, 2021; Accepted: February 2, 2021; Published online: February 2, 2021.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Schizophrenia is a chronic, recurrent and highly decimating mental illness which needs a long-term maintenance treatment to prevent relapse and recurrence as well as intensive acute phase treatment due to severe psychotic and behavioral symptoms. The mainstay of treatment is pharmacological therapy using various antipsychotics including first- (FGAs) and second-generation antipsychotics (SGAs) which have different pharmacokinetic and pharmacodynamic property leading to differential presentation of adverse events (AEs) and different effects on diverse symptom domain such as negative symptoms, cognitive symptoms and cormorbid symptoms. Major treatment guidelines suggest the use of antipsychotic monotherapy (APM) as a gold standard in the treatment of schizophrneia. However, the effects of APM is inadequate and less potent to achive symptom remission as well as functional recovery in real practice which has been clearly and consistently reported in numerous randomized, controlled clinical trials (RCTs), large practical trials, independent studies and metaanalyses till today. Therefore antipsychotic polypharmacy (APP) using combination of two or more antipsychotics regardless of the class of antipsychotics has been also commonnly utilized for many reasons in real world practice. However, APP has also critical and numerous shorcomnigs including increase of total psychotics including antipsychotics, high-doses of antipsychotics used, poor compliance, drug-drug interaction and risks for developing AEs, all of which are paradoxially and ultimately related to poor clinical outcomes, whereas APP has also substantial advantages in reduction of rehospitalization, severe psychophathology and targeted control of concurrent symptoms. Hence, under currently limited therapeutic options, it is crucial to properly utilize APP based on risk/benefit with full understanding of pharmacologica/clinical issues of APP in order to maximaize its clinical usefulness and minimize unwanted clinical outcomes leading to best-achievable treatment outcomes in the treatment schizophrenia. The present paper intends to address intriguing but also critical pharmacological and clinical issues that are overlooked or little-known to us in the use of APP.
Keywords: antipsychotic, schizophrenia, polypharmacy, issues

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