To evaluate the efficacy of memantine in improving clinical outcomes in patients with Parkinson's disease (PD).

Memantine, an NMDA receptor antagonist, has been investigated for its potential benefits in PD, particularly for cognitive and motor symptoms. Despite several clinical trials, its overall impact remains uncertain.

PubMed was searched for randomized controlled trials of memantine in Parkinson’s disease. Outcomes included UPDRS-III (ON), NPI, ADL (DAD, ADL23, UPDRS-II), PDQ-39, and CGIC. Studies reporting sample size, mean, and SD for both groups were analyzed. Standardized mean differences (SMD) and mean differences (MD) were pooled using an inverse-variance method under fixed- and random-effects models. Heterogeneity was assessed with I2 statistic.

Five trials (PMID: 6734455, 19520613, 20729148, 21193343, 23077087) were included, with memantine doses ranging from 10 to 20 mg/day. Pooled analyses showed no significant effect on motor function (UPDRS-III ON: MD 0.17; 95% CI –1.27 to 1.61; I² = 0%) or neuropsychiatric symptoms (NPI: MD –1.88; 95% CI –5.09 to 1.34; I² = 0%). Similarly, activities of daily living were unchanged (ADL: SMD –0.01; 95% CI –0.24 to 0.22; I² = 0%). However, a small but statistically significant improvement was observed in global clinical impression (CGIC: MD –0.40; 95% CI –0.77 to –0.03; I² = 0%). No heterogeneity was detected across outcomes.

Memantine showed no significant benefit for motor symptoms, neuropsychiatric outcomes, or activities of daily living in PD. A small but statistically significant improvement was observed in global clinical impression, though its clinical relevance remains uncertain. Larger, high-quality trials are needed to clarify the role of memantine in PD management.