# Memantine for the treatment of obsessive-compulsive disorder: a systematic review and narrative synthesis

## TL;DR

This paper reviews the use of memantine for obsessive-compulsive disorder, finding potential benefits but noting limitations due to small studies and mixed results.

## Contribution

A systematic review and narrative synthesis of memantine's use in OCD, highlighting methodological gaps and mixed tolerability/effectiveness outcomes.

## Key findings

- Memantine may offer therapeutic benefits for OCD, but evidence is limited by small sample sizes and geographical clustering.
- Higher memantine doses were associated with increased side effects, while lower doses showed poorer efficacy.
- Only one study assessed treatment-refractory OCD and reported significant improvement with long-term memantine.

## Abstract

Obsessive-compulsive disorder (OCD) is a chronic psychiatric condition for which a substantial proportion of patients do not respond adequately to first-line treatments. This review thus aimed to critically appraise the clinical literature examining memantine in obsessive-compulsive disorder, with a particular focus on individual study design, dosing strategies, tolerability, and methodological limitations.

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. A second, identical literature search was conducted in August 2025 covering March 2024 to August 2025. In total, 10 studies were included in the narrative synthesis.

Our findings suggest that memantine may offer therapeutic benefits for OCD. Methodological issues, however, such as small sample sizes, strong geographical clustering, the 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 being associated with increased side effects while lower doses appeared better tolerated but elicited a poorer efficacy, although evidence was mixed. Only one study rigorously assessed treatment-refractory OCD and reported significant symptomatic improvement following longer-term memantine administration. Baseline severity, treatment expectancy, and concurrent cognitive-behavioural therapy were also identified as factors that may mediate these effects.

Overall, current evidence does not support the routine use of memantine for OCD. However, it does highlight specific methodological considerations and priorities for future rigorous 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.

Not applicable.