Exploring Hidden Issues in the Use of Antipsychotic Polypharmacy in the Treatment of Schizophrenia

Abstract

The mainstay of schizophrenia treatment is pharmacological therapy using various antipsychotics including first-and second-generation antipsychotics which have different pharmacokinetic and pharmacodynamic property leading to differential presentation of adverse events (AEs) and treatment effects 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 schizophrenia. However, the effects of APM is inadequate and less potent to achieve symptom remission as well as functional recovery in real practice which has been consistently reported in numerous controlled clinical trials, large practical trials, independent small studies and systematic reviews till today. Therefore antipsychotic polypharmacy (APP) regardless of the class of antipsychotics has been also commonly utilized for many reasons in real world practice. However, APP has also crucial pitfalls 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 paradoxically related to poor clinical outcomes, whereas APP has also substantial advantages in reduction of re-hospitalization, severe psychopathology and targeted control of concurrent symptoms. Given currently limited therapeutic options, it is also important to properly utilize APP in order to maximize its clinical utility and minimize its risk for better treatment outcomes for patients with schizophrenia, based on risk/benefit with full understanding of pharmacological and clinical issues on APP. The present paper intends to address intriguing and important issues in the use of APP in real world practice.

Potential Drug-Drug Interactions among Patients with Schizophrenia Spectrum Disorders: Prevalence, Association with Risk Factors, and Replicate Analysis in 2021

“…Monotherapy with antipsychotics is the standard treatment recommended in many treatment guidelines [ 4 , 5 ]. However, because of the limited efficacy of antipsychotic monotherapy, antipsychotic polypharmacotherapy is commonly used, and the global median rate of antipsychotic polypharmacotherapy has been estimated to be approximately 20% [ 6 ], with substantial variation across geographic regions [ 7 ]. Patients with SSDs have a high prevalence of comorbidities including obesity, diabetes, hypertension, and dyslipidemia [ 8 ].…”

A Survey Study on Clinicians’ Rationale and Attitude Towards the Prescription of Antipsychotic Polypharmacy in the East Perth Metropolitan Area in Western Australia

“…Antipsychotic monotherapy (APM) was officially recommended by reputable treatment guidelines, randomised cohort studies, and well-designed clinical trial evidence as the gold-standard therapy in routine psychiatry practices [ 4 ]. However, in the real clinical setting, APM remains a substantial challenge despite several pharmacologic innovations, and its efficacy is not as satisfactory or as yielding, especially in treatment-resistant cohorts [ 5 , 6 ]. This, therefore, justifies the use of a second treatment option, antipsychotic polypharmacy (APP).…”

“…This, therefore, justifies the use of a second treatment option, antipsychotic polypharmacy (APP). Despite the weak and controversial evidence supporting the use of APP, it is clinically recommended as the cornerstone for successful outcomes, especially in the acute psychotic phase, prevention of relapse, and addressing antidopaminergic activities in patients in the acute mental health setting [ 6 ].…”

“…Approximately two decades ago, APP was labelled "a legitimate but unnecessary use of psychotropic agents" [ 13 ], with the reported negative associations to QTc prolongation, extrapyramidal symptoms, cognitive dysfunction, potential drug interactions, poor medication adherence, increased financial burden (personal, family, and public health), and increased risk of metabolic syndrome [ 6 ]. Interestingly, despite the highlighted side effects, recent studies continue to indicate that APP continues to enjoy enormous patronage from clinicians [ 2 , 13 ].…”

Efficacy of Olanzapine in Anxiety Dimension of Schizophrenia: A Systematic Review of Randomized Controlled Trials

“…Schizophrenia is a common, chronic and severe mental illness defined by the presence of delusions, hallucinations, and disorganized behavior (positive symptoms); by the presence of apathy, avolition, social withdrawal (negative symptoms); and by cognitive disorganization [ 1 , 2 ]. Further complicating the clinical picture of schizophrenia as well as understanding the boundaries and etiology of this condition is the substantial psychiatric comorbidity [ 3 , 4 ].…”