New horizons for obsessive-compulsive disorder drug discovery: is targeting glutamate receptors the answer?

ABSTRACT

Introduction

Over the past decade, glutamate has emerged as a prominent focus in the field of obsessive-compulsive disorder (OCD) pathophysiology. A convergence of evidence from genetic, preclinical, and clinical studies points to glutamatergic dysfunction as a key feature of this condition. In light of these findings, there has been a growing interest in exploring the potential of glutamatergic agents in the treatment of OCD.

Areas covered

This paper reviews the literature on glutamate transmission in OCD. In addition, the authors examine the results of clinical trials investigating the efficacy of glutamatergic agents in the treatment of OCD patients.

Expert opinion

Along with the recognition of neuroinflammation in the brain in OCD, the evidence of glutamate dysfunction represents one of the most promising recent discoveries for understanding the mechanisms involved in OCD. The importance of this discovery lies primarily in its pharmacological implications and has led to intense research activity in the field of glutamatergic agents. While this research has not yet had a substantial clinical impact, targeting glutamate receptors remains a promising horizon for the successful treatment of OCD patients.

KEYWORDS:

• OCD
• glutamate
• treatment-resistant
• NMDA
• ketamine
• troriluzole
• neuobiology

Article highlights

• Evidence from preclinical studies suggests a role for glutamate in OCD-like behaviors

• Neuroimaging and genetic studies on OCD patients converged on a glutamate transmission dysfunction in brain areas involved in OCD pathophysiology

• Several glutamatergic agents have been investigated for the treatment of resistant OCD. Among these, NMDA receptor antagonists in particular have shown promising results.

• The main limitation of current studies is represented by the small sample size. However, larger and multi-center trials are underway and new glutamatergic agents are being investigated

• Head-to-head trials between glutamatergic agents and other augmentation strategies are needed in order to establish a potential treatment algorithm for resistant patients

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

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

Additional information

Funding

This paper was not funded.