SUMMARY Aripiprazole, brexpiprazole and cariprazine are partial dopamine (and serotonin) agonists developed as novel antipsychotics. This article discusses their pharmacology, evidence on their licensed and off-licence uses (including psychosis, mania, bipolar depression, Tourette syndrome and autism spectrum disorder) and side-effects. In schizophrenia, they have a low risk of Parkinsonism or hyperprolactinaemia, cause modest increases in body weight and are of moderate efficacy.

SUMMARY This article discusses dopamine partial agonism, which is the main mechanism of action of the psychiatric drugs aripiprazole, brexpiprazole and cariprazine. It outlines the principles of receptor theory and the structure of dopamine receptors; characterises agonists, antagonists and partial agonists; and summarises the dopamine hypothesis of psychosis and the role of dopamine and serotonin in depression.

SUMMARY Partial agonists such as aripiprazole are often used in addition to a full antagonist such as amisulpride, risperidone or olanzapine in an attempt to mitigate side-effects such as sedation, hyperprolactinaemia and weight gain. However, there can be unintended consequences, including worsening of psychosis. Moreover, previous exposure to a partial agonist may impair the subsequent response to a potent antipsychotic such as haloperidol used to control symptoms of relapse. To understand the mechanisms involved, a method is needed to compare potency in the pharmacological effects of different drugs used in combinations. This article is intended to explore and explain the theoretical principles based on the dopamine hypothesis of schizophrenia. We apply the method to analyse a recently described trial in which two full antagonists (olanzapine and amisulpride) are compared individually and in combination.

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.