Predictors of Clinical Response to Memantine Augmentation in Patients with Obsessive-Compulsive Disorder

Abstract

Background: Obsessive-compulsive disorder (OCD) is a chronic and disabling disorder. Selective serotonin reuptake inhibitors (SSRIs) are effective in treating OCD. However, treatment response to SSRIs is often slow and incomplete in patients with OCD. Enhancing therapeutic response by adding other medications, including memantine, has been associated with favorable clinical outcomes in treatment-resistant cases. Objectives: This study aimed to investigate demographic and clinical factors that may predict response to memantine-augmented treatment in patients with treatment-resistant OCD. Methods: A naturalistic retrospective study was conducted in 94 patients with treatment-resistant OCD who received memantine-augmented treatment at 2 psychiatric clinics in Rasht from 2018 to 2023. Clinical response to memantine augmentation was defined as a 30% reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores compared with baseline. Demographic and clinical variables were compared between 42 individuals in the clinical response group and 52 individuals in the nonclinical response group. Data were analyzed using simple logistic regression. Results: There were no significant differences between the 2 groups regarding response to memantine (P > 0.05). Based on simple logistic regression analysis, demographic and clinical variables, including type of OCD, duration of illness, age at onset, family history of OCD, comorbidity, disorder severity, and medication treatment strategies, were not identified as significant predictors of treatment response to memantine (P > 0.05). Conclusions: The absence of identifiable predictors suggests that the therapeutic effect of memantine may be broadly applicable and not restricted to an identifiable clinical subgroup. The underlying mechanisms of response to glutamatergic modulation may be more subtle than what is measurable by conventional clinical criteria. Our negative findings underscore the complexity and heterogeneity of the pathophysiology of treatment-resistant patients. Future research should focus on larger, multicenter samples to identify smaller effect sizes, enable robust subgroup analyses, and explore prospective biomarkers related to glutamate signaling.