Brexpiprazole is a new atypical antipsychotic indicated for the treatment of schizophrenia in adult patients. It is currently available on the Pharmaceutical Benefits Scheme (PBS) as a streamlined authority item.
Like the structurally related agent, aripiprazole, brexpiprazole is a partial agonist at the dopamine D2 receptor. Partial D2 receptor agonists can behave as functional agonists or functional antagonists. In conditions associated with high concentrations of extracellular dopamine, partial agonists compete with endogenous dopamine to produce functional antagonism. This may be therapeutic in alleviating the positive symptoms of schizophrenia mediated by high dopamine levels in the mesolimbic system. Conversely, in areas of proposed hypoactive dopaminergic transmission such as the prefrontal cortex, a partial agonist may functionally act as an agonist to alleviate negative symptoms.
The intrinsic activity of brexpiprazole at D2 receptors is lower than that of aripiprazole. Therefore, it has a lower potential to generate D2 agonist-like effects such as akathisia, insomnia, restlessness, and nausea. Its potential to induce D2 antagonist-like effects such as extrapyramidal symptoms, hyperprolactinaemia, and tardive dyskinesia, is also likely to be much lower than antipsychotics that are full D2 antagonists. The unique serotonergic and noradrenergic binding profile of brexpiprazole may also contribute to greater tolerability. While brexpiprazole may cause sedation, the incidence is expected to be low due to its relatively low binding affinity for histamine H1 receptors.
An open-label exploratory study reported a response rate of 60.9% for brexpiprazole, compared to 48.5% for aripiprazole. However, this study was not sufficiently powered for direct comparison. Further comparative studies are required to evaluate the differences between these two agents.
- Abilify® (aripiprazole) Australian approved product information. Chatswood: Otsuka Australia. Approved December 2016.
- Citrome L, Ota A, Nagamizu K, Perry P, Weiller E, Baker R. The effect of brexpiprazole (OPC-34712) and aripiprazole in adult patients with acute schizophrenia: results from a randomized, exploratory study. Int Clin Psychopharmacol. 2016; 31(4): 192-201.
- Rexulti® (brexpiprazole) Australian approved product information. North Ryde: Lundbeck. Approved May 2017.
- Weinstein JJ, Chohan MO, Slifstein M, Kegeles LS, Moore H, Abi-Dargham A. Pathway-Specific Dopamine Abnormalities in Schizophrenia. Biol Psychiatry. 2017; 81(1): 31-42.