Reducing Addiction in Bipolar Disorder via Hacking the Dopaminergic System

Abstract

The dopaminergic system plays a central and decisive role in substance use disorder (SUD), bipolar disorder (BD), and possibly in a subgroup of patients with refractory depression. Common genetic markers and underlying cellular processes, such as kindling, support the close link between these disorders, which is also expressed by the high rate of comorbidity. Although partial dopamine agonists/antagonists acting on D₂ and D₃ receptors have an established role in treating BD, their usefulness in SUD is less clear. However, dopamine D₃ receptors were shown to play a central role in SUD and BD, making D₂/D₃ partial agonists/antagonists a potential target for both disorders. This narrative review examines whether these substances bear the promise of a future therapeutic approach especially in patients with comorbid BD and SUD.

Keywords: antipsychotic; bipolar disorder; cariprazine; partial agonist; psychopharmacotherapy; substance use disorder (SUD).

Figure 1

Occupancy of D₂ and D₃ receptors of antipsychotics. The cariprazine and aripiprazole data come from a PET study involving healthy volunteers that aimed to assess the D3 receptor occupancy of cariprazine and aripiprazole at doses that attain similar D2 receptor occupancy by both drugs. This was assessed using two different methods, and the data presented here is the average of the outcome of these methods. The brexpiprazole data comes from a PET study involving schizophrenia patients.