Abstract
Antipsychotic polypharmacy/drug combination treatment (APP) is a remarkably common practice in the schizophrenia context, given the lack of general support in treatment Guidelines. There is also a vast literature on APP outcomes, but a paucity of high-quality evidence-based data to guide and optimize adequate use of APP. This seems particularly true regarding many pharmacology-based considerations involved in APP treatment strategies. This paper first briefly summarizes clinical literature related to the use of APP. Against this backdrop, the pharmacological target profile features are then described of frequently used antipsychotic agents, in relation to estimated free plasma exposure levels at clinically efficacious dosing. APP strategies based on the properties of these drugs are then scrutinized and gauged within the background literature framework. The anticipated usefulness of APP from the pharmacological standpoint is detailed regarding efficacy, adverse effect (AE)/tolerability, and safety perspective, including why, when, and how it may be used to its advantage. For the purpose, a number of theoretically beneficial combinations as well as instances with suboptimal—and even futile—APP approaches are exemplified and discussed from the rational pharmacodynamic and pharmacokinetic pros and cons point-of-view. In this exposé, particular attention is paid to the utility and features of 3rd Generation Antipsychotic dopamine (DA) D2-D3 agonists within an APP setting.
Highlights
In an ideal pharmacotherapy setting, schizophrenia treatment with a single antipsychotic agent would be preferable
Antipsychotic PolyPharmacy (APP) treatment may be useful in selected patients when switch is not desired or feasible, but is NOT to be
The writing of this report was in part sponsored by Recordati, but the company had no influence on data collection, analysis, content, or interpretations
Summary
In an ideal pharmacotherapy setting, schizophrenia treatment with a single antipsychotic agent would be preferable. Whereas combinations of (FGA and SGA) D2 receptor antagonists may be challenging, available data discussed in this account indicate that from the pharmacological perspective selected APP, in particular based on SGA + TGA, may be efficacious, tolerable, safe, as well as useful in a preventive, relapse/rehospitalization context Within this APP framework, a PD comparison between the TGA:s CAR and ARI suggests that while both display high affinity partial agonist activity at the D2 receptors, CAR displays even higher affinity for the D3 than the D2 sites and is nearly 10fold more potent than ARI at D3 receptors [e.g., [22]]. Until further studies to assess this prediction, it must remain purely speculative
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