High dose antipsychotic polypharmacy and dopamine partial agonists - time to rethink guidelines?

REYNOLDS, Gavin (2021). High dose antipsychotic polypharmacy and dopamine partial agonists - time to rethink guidelines? Journal of Psychopharmacology, 35 (9), 1030-1036.

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Abstract

Guidelines for the treatment of schizophrenia limit the use of antipsychotic agents to clinically-established maximum doses. This acknowledges both the absence of additional efficacy of dopamine D2 receptor antagonists above a receptor occupancy threshold, and the increases in side effects that can occur at higher doses. These limits restrict the dosing of combinations of antipsychotics as they do single agents; drugs sharing the major antipsychotic mechanism of D2 receptor antagonism will act additively in blocking these receptors. Several newer antipsychotic drugs, including aripiprazole and cariprazine, act as partial agonists at the D2 receptor site and avoid action at several other receptors, effects at which are responsible for some non-dopaminergic adverse effects. This pharmacology imparts different characteristics to the drugs resulting often in a more favourable side effect profile. Their partial agonism, along with high affinities for the D2 receptor, also means that these drugs given adjunctively may in part replace, rather than enhance, the D2 antagonism of other antipsychotic agents. This can result in an improvement in certain side effects without loss of antipsychotic efficacy. This article makes the case for distinguishing the D2 partial agonists from antagonists in defining maximum doses of combined treatments, which would increase the options available to the prescriber, emphasising that pharmacological mechanisms need to be understood in identifying optimal treatments for psychotic illness.

Item Type:	Article
Additional Information:	** Embargo end date: 14-07-2021 ** From SAGE Publishing via Jisc Publications Router ** Licence for this article starting on 14-07-2021: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: pissn 0269-8811; eissn 1461-7285 **Article IDs: publisher-id: 10.1177_02698811211026456 **History: published_online 14-07-2021
Uncontrolled Keywords:	Critique/Commentary, Antipsychotic agents, adjunctive treatment, dopamine D2 receptor, antagonists, partial agonists
Identification Number:	https://doi.org/10.1177/02698811211026456
Page Range:	1030-1036
SWORD Depositor:	Colin Knott
Depositing User:	Colin Knott
Date Deposited:	13 Sep 2021 11:23
Last Modified:	28 Sep 2021 09:00
URI:	https://shura.shu.ac.uk/id/eprint/29046

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