Aripiprazole: examining the clinical implications of D2 affinity

Abstract

Schizophrenia is a prevalent psychiatric illness, which causes significant financial and social burden on the population overall. The development of second generation antipsychotics, such as Aripiprazole, Risperidone, and Paliperidone, has changed treatment practice for many psychiatrists. Aripiprazole has extremely high binding affinity for the dopamine D2 receptor, which is the receptor thought to be responsible for the antipsychotic effect, although Aripiprazole is not the most potent of the second generation antipsychotics. In theory, Aripiprazole could displace or outcompete other, more potent antipsychotics, prompting decreased antipsychotic effect. We describe a proposed case of this phenomenon, Ms. A. We describe how Aripiprazole may have caused a worsening of psychiatric symptoms by blocking the antipsychotic effects of Paliperidone due to its strong binding affinity for the D2 receptor. Aripiprazole has a high affinity for the D2 receptor, but may have a lesser reduction of psychotic symptoms compared to other antipsychotics. Prescribers should be aware of this potential interaction and carefully consider initiating long-acting injectable forms of Aripiprazole to avoid this phenomenon. Int Clin

The challenge of managing difficult to treat psychiatric conditions

“…The appropriate pharmacologic modulation of dopamine D2 receptors is also the topic of the case report by Anam et al (2022) in this issue, which describes a patient showing a psychotic worsening after aripiprazole treatment. Aripiprazole is known to be a very useful therapeutic option in the treatment of schizophrenia.…”

“…This is not the only caution to be adopted, also the combination of aripiprazole and complete D2 blockers such as risperidone or haloperidol has poorly known effects, as recently reviewed (Lippi et al, 2022). The case report by Anam et al (2022) in this issue exemplifies the risks of a potentially inappropriate aripiprazole management, specifically in the long-acting formulation. In the reported case, aripiprazole was prescribed because of poor tolerability of previous treatments and quickly administered in the long-acting formulation, after a brief phase of oral prescription.…”