The role of the D3 dopamine receptor and its partial agonist cariprazine in patients with schizophrenia and substance use disorder

ABSTRACT

Introduction

Comorbidity of substance use disorder (SUD) with schizophrenia, referred to as dual disorder (DD), significantly increases morbidity and mortality compared to schizophrenia alone. A dopaminergic dysregulation seems to be a common pathophysiological basis of the comorbidity.

Areas covered

This article reports the current evidence on the role of dopamine dysregulations in DD, the pharmacological profile of cariprazine, a partial agonist of D3 and D2 dopamine receptors, and first clinical observations that may support its usefulness in the therapy of DD. PubMed/MEDLINE was searched for the keywords ‘cariprazine,’ ‘schizophrenia,’ ‘dual disorder,’ ‘dopamine,’ and ‘dopamine receptor.’ Preclinical and clinical studies, and reviews published in English were retrieved.

Expert opinion

Although the management of DD remains challenging, and the evidence for pharmacologic treatments is still unsatisfactory, cariprazine may be a candidate medication in DD due to its unique mechanism of action. Preliminary clinical experiences suggest that cariprazine has both antipsychotic and anticraving properties and should be considered early in patients with DD.

KEYWORDS:

• Dopamine
• D2
• D3
• cariprazine
• schizophrenia
• dual disorder

Article highlights

• Comorbidity of schizophrenia with substance use disorder has poorer clinical outcomes and significantly increased morbidity and mortality compared to schizophrenia alone.

• Cariprazine is a third-generation atypical antipsychotic acting as a partial agonist of D3 and D2 dopamine receptors, with higher binding affinity for D3, with affinity for serotonin 1A (5-HT1A) and serotonin 2A (5-HT2A) receptors.

• D3 receptors are upregulated in substance users and dysregulated in several mental disorders, including schizophrenia.

• Partial agonists to D2/D3 receptors, especially with a high affinity to D3 such as cariprazine, are promising candidate drugs in DD but need more controlled clinical research before routine use can be recommended.

Acknowledgments

The author wishes to acknowledge Fabio Perversi and Laura Brogelli (Polistudium Srl, Milan, Italy) for medical writing and Valentina Attanasio and Aashni Shah (Polistudium Srl, Milan, Italy) for linguistic and editorial assistance. Medical writing and editorial assistance were supported by Recordati.

Declaration of interest

Within the last 3 years, H Grunze has received honoraria for expert opinion, lecturing, and advisory board participation from Janssen-Cilag, Recordati, and Sanofi. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.