Role of Glutamatergic Modulators in the Treatment of Obsessive Compulsive and Related Disorders

Abstract

Due to the shared phenomenology and research findings related to disorders like obsessive-compulsive disorder (OCD), trichotillomania (TTM), body dysmorphic disorder (BDD), skin picking disorder (SPD), hoarding disorder (HD), and OCD, these conditions are collectively classified as Obsessive-Compulsive and Related Disorders (OCRDs) in the DSM-5. Despite having distinct features from OCD in terms of course and treatment outcomes, they are categorized together. The etiology of OCRDs remains incompletely understood, and information on their treatment is limited. Traditional pharmacological approaches often fall short in addressing the needs of many OCRD patients, necessitating alternative strategies. Recent research has shed light on a potential imbalance in glutamate, a crucial excitatory neurotransmitter in the brain, among certain patients with OCRDs. Findings from these studies suggest that glutamate modulators may be beneficial for individuals who do not respond to standard pharmacotherapeutic interventions. While no glutamate modulator has conclusively proven effective for OCD, promising results have been noted for memantine and riluzole. The evidence surrounding N-acetylcysteine (NAC) also positions it as a reasonable consideration for some patients. Noteworthy research on D-cycloserine (DCS) and ketamine has indicated potential benefits, and investigations into the off-label use of these pharmacological agents, originally approved for other indications, have been particularly focused on refractory OCRDs. It is essential to highlight that these drugs operate through diverse and, in some cases, opposing mechanisms. However, it is crucial to acknowledge that the existing studies on the use of these drugs in OCRDs are still insufficient. A more in-depth exploration of glutamate imbalance in the etiology of OCRDs is needed to better understand the role of glutamate modulators in treatment.

Keywords

• obsessive compulsive and related disorders
• glutamate
• d-cycloserine
• ketamine
• n-acetylcysteine