Is there a therapeutic potential in combining bupropion and naltrexone in schizophrenia?

ABSTRACT

Introduction

A sustained-release tablet composed of a combination of the dopamine and norepinephrine reuptake inhibitor bupropion (BUP) and the µ-opioid receptor antagonist naltrexone (NAT) is marketed under the brand name Contrave by Orexigen Therapeutics for appetite control. Minimal literature is available regarding the use of combination bupropion and naltrexone (BUPNAT) in individuals with schizophrenia.

Areas Covered

In this review, we propose a theoretical model where BUPNAT may have a therapeutic effect in the treatment of schizophrenia. We explore the pathways targeted by the constituent drugs BUP and NAT and summarize the literature on their efficacy and possible adverse effects. We then look at the potential use of BUPNAT in schizophrenia.

Expert Opinion

Research has hinted that BUP’s dopaminergic properties affect the same striatal pathways involved in schizophrenia. NAT, via opioid receptor antagonism, indirectly increases striatal dopamine release by disinhibiting nicotinic acetylcholine receptors. As such, we hypothesize that BUPNAT can have a therapeutic effect in schizophrenia, particularly on negative symptoms. We also suggest that it may ameliorate comorbidities frequently seen in this group of patients, including obesity, smoking, and substance use. Further research and clinical data are needed to elucidate the potential clinical benefits of BUPNAT in the treatment of schizophrenia.

KEYWORDS:

• bupropion
• metabolic syndrome
• naltrexone
• psychosis
• schizophrenia
• treatment

Article highlights

• BUPNAT is an oral extended-release tablet composed of the dopamine and norepinephrine reuptake inhibitor bupropion (BUP) and the µ-opioid receptor antagonist naltrexone (NAT).

• In this review, we propose a theoretical model for a therapeutic effect for BUPNAT in the treatment of schizophrenia.

• NAT can help manage positive and negative symptoms of schizophrenia, especially when combined with antipsychotics.

• BUP may modestly alleviate negative symptoms of schizophrenia.

• BUPNAT can be considered a safe medication in individuals with schizophrenia, with a low propensity for adverse neuropsychiatric events.

• BUPNAT may contribute to reducing the morbidity and mortality associated with schizophrenia by targeting obesity and smoking.

Acknowledgments

We would like to acknowledge Ms. Christina Ishak for her help in the design of the figures.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed they are a consultant for BioXcel Therapeutics. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.