Partial agonists of dopamine receptors: clinical effects and dopamine receptor interactions in combining aripiprazole with a full antagonist in treating psychosis

Abstract

SUMMARY Partial agonists of dopamine receptors are used in combination with full antagonists in treating psychosis, either to mitigate side-effects or in the hope of increasing effectiveness. We examine how combinations may affect the occupancy of D2/D3 dopamine receptors and explore how these can explain the outcomes in the light of the dopamine hypothesis of psychosis. The combinations considered here are from published studies combining aripiprazole with amisulpride, with risperidone in people with hyperprolactinaemia and with olanzapine to mitigate weight gain. We discuss possible worsening of symptoms by the addition of a partial agonist or switching. We also examine the potentially adverse interaction with a full antagonist such as haloperidol given during a subsequent relapse to control severe agitation.

Rhyme or reason in therapeutics

“…Finally, to add further reason to the rhyme of prescribing antipsychotics, a series of papers address the use of partial agonists at dopamine receptors and alone or in combination with other antipsychotics (Cookson 2023a(Cookson , 2023b(Cookson , 2023c(Cookson , 2023d.…”

“…The third discusses the use of a combination of two antipsychotics in the treatment of schizophrenia, using a formula and applying data from positron emission tomography (PET) scans showing occupancy by various antipsychotics (Cookson 2023c). And finally, the fourth culminates in the application of the same formula to the combination of a full antagonist with a partial agonist (Cookson 2023d).…”

Partial agonists of dopamine receptors: theoretical principles of combining antipsychotics including partial agonists to treat schizophrenia

“…In three other articles in this issue we review the nature of partial agonism of dopamine receptors (Cookson 2023a) and the qualities of three partial agonists, aripiprazole, brexpiprazole and cariprazine (Cookson 2023b), and discuss the combination of a partial agonist with a full antagonist (Cookson 2023c).…”

“…Furthermore, clozapine cannot be included in this model of drug interactions because its additional efficacy in otherwise non-responsive patients likely depends on mechanisms other than D 2 /D 3 receptor antagonism, and occupancy in acute treatment is less than 70% (Farde 1992). Hence, any displacement by aripiprazole will not reduce blockade of dopamine (see Cookson et al, 2023c).…”