Memantine Augmentation in Obsessive-Compulsive Disorder: A Systematic Review and Meta-analysis

AI Summary

Adjunctive memantine did not significantly reduce OCD symptoms versus placebo (mean difference −3.74 points, 95% CI −9.95 to 2.47) with high heterogeneity.
In treatment resistant OCD there was a larger but imprecise effect (~ −8.85 points), based on few trials, supporting hypothesis generation only.
Tolerability similar to placebo; responder analyses favoured memantine but were statistically unstable; no excess adverse events or discontinuations identified.

AI Summary

OBJECTIVE: Since glutamatergic dysregulation is implicated in OCD, we systematically reviewed and meta-analysed randomized controlled trials (RCTs) comparing adjunctive memantine versus placebo for OCD.

Trials in treatment-resistant populations showed a larger but imprecise estimate (≈ -8.85 points), whereas non-resistant trials showed minimal added benefit (≈ -1.26 points); this subgroup observation was based on two RCTs, and meta-regression was underpowered and non-significant.

Basic summary

CNS Drugs. 2026 Jul 22. doi: 10.1007/s40263-026-01318-4. Online ahead of print.

ABSTRACT

BACKGROUND: Obsessive-compulsive disorder (OCD) remains challenging to treat despite established treatments.

METHODS: We searched CENTRAL, Embase, MEDLINE, PsycINFO, PubMed, Web of Science, Scopus, and trial registries from inception to September 2025 for RCTs of adjunctive memantine in adults with OCD [PROSPERO: CRD420251147106]. The primary outcome was endpoint Yale-Brown Obsessive Compulsive Scale score. Random-effects models used REML estimation with Hartung-Knapp-Sidik-Jonkman confidence intervals. Risk of bias was assessed with RoB 2 and certainty of evidence with GRADE.

RESULTS: Six RCTs (n = 288; 8-16 weeks; 5-20 mg/day) met inclusion criteria. Overall, memantine did not produce a statistically significant symptom reduction versus placebo (pooled mean difference -3.74 points, 95% confidence interval [CI] -9.95 to 2.47), with high heterogeneity (I² = 97.9%). Trials in treatment-resistant populations showed a larger but imprecise estimate (≈ -8.85 points), whereas non-resistant trials showed minimal added benefit (≈ -1.26 points); this subgroup observation was based on two RCTs, and meta-regression was underpowered and non-significant. Responder outcomes favored memantine but were statistically unstable (risk ratio [RR] 3.62, 95% CI 0.16-80.71). Tolerability outcomes did not identify clear excess adverse events, excess discontinuations for adverse events, or higher all-cause discontinuation (RR 1.04, 95% CI 0.82-1.31).

CONCLUSIONS: Memantine is not supported for routine use in unselected OCD. In treatment-resistant OCD, current evidence supports a hypothesis-generating signal that may justify cautious off-label discussion when established augmenters are unsuitable. An adequately powered RCT in refractory OCD is warranted.

PMID:42484816 | DOI:10.1007/s40263-026-01318-4

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