Evaluating the Role of Memantine in the Treatment of Obsessive-Compulsive Disorder

Objective This literature review aimed to: (1) investigate the role of memantine as a treatment for obsessive-compulsive disorder (OCD), with a particular focus on patients with treatment-refractory OCD and (2) evaluate the prevalence and tolerability of adverse side-effects. Methods A structured literature search of MEDLINE was conducted in March 2024 from database inception to March 2024. Titles, abstracts, and full texts were screened against predefined inclusion criteria, and relevant studies were synthesised narratively. An updated literature search was conducted in August 2025 employing identical methods covering March 2024 to August 2025. In total, 10 studies were included in the narrative synthesis. Results Our findings suggest that memantine may offer therapeutic benefits for OCD. Methodological issues, however, such as exclusion of dropout data and limited use of intention-to-treat analyses, restrict the generalisability of the reported outcomes. Tolerability varied significantly by dose, with higher doses associated with increased side effects while lower doses appeared better tolerated but elicited a poorer efficacy. Only one study rigorously assessed treatment-refractory OCD and reported significant improvement following longer-term memantine administration. Baseline severity, treatment expectancy, and concurrent cognitive-behavioural therapy were also identified as factors that could mediate these effects. Conclusion While the current evidence fails to support the routine use of memantine for OCD, particularly in light of methodological heterogeneity and small sample sizes, its potential warrants further investigation. Future randomised controlled trials with larger samples, longer follow-ups, and standardised dosing protocols are needed to clearly determine memantine’s role in OCD management.