The position statement of the Working Group of the Polish Psychiatric Association on the use of D2/D3 dopamine receptor partial agonists in the treatment of mental disorders.Psychiatr Pol. 2021 Oct 31; 55(5):941-966.PP
Aripiprazole, cariprazine and brexpiprazole are antipsychotic drugs (APD) whose action is associated with partial agonism at the dopamine D2/D3 receptors. They are increasingly more widely used in clinical practice, also off-label. The aim of this article is to present the current state of knowledge on the use of these drugs in the treatment of mental disorders. The position statement was developed by the panel of experts appointedby the Executive Board of the Polish Psychiatric Association, consisting of individuals with many years of experience in treating patients with mental disorders. The evaluation included the analysis of literature databases (Medline, Embase, Cochrane) and information obtained from metaanalyses and summaries of product characteristics. A key property of D2/D3 partial agonists is that they display diverse effects on dopamine pathways: (a) blockade of mesolimbic signalling that is overactive in the acute phase of schizophrenia and mania, (b) stimulation of mesocortical pathways with an improvement (or at least with no deterioration) of cognitive functions and negative symptoms, (c) no blockade of the tuberoinfundibular pathway and, consequently, low risk of increased prolactin secretion, (d) no blockade of nigrostriatal pathway and, consequently, low risk of extrapyramidal symptoms. Selective profile of action and intrinsic activity at dopamine D2 (aripiprazole > brexpiprazole) and D3 (cariprazine) receptors in combination with the lack of antihistamine and anticholinergic properties make aripiprazole, brexpiprazole and cariprazine different form other APD in terms of their safety and tolerability. This is the reason for the increasing use of these drugs in the treatment of schizophrenia and mood disorders, and in the case of aripiprazole also in obsessive-compulsive, autism-spectrum and tic disorders.