Peer-reviewedCC BY 4.0Dementia & Neuropsychologia2 Nov 2026

The efficacy of NMDA receptor antagonists in neuropsychiatric and non-motor symptoms of Parkinson’s disease: a systematic review

Jan Arel Solomon Orlino¹
Ma. Lourdes Corrales-Joson^1,2

¹University of Santo Tomas Hospital, Department of Neuroscience and Behavioral Medicine, Manila, Philippines.
²University of Santo Tomas, Faculty of Medicine and Surgery, Department of Neuroscience and Behavioral Medicine, Manila, Philippines.

Abstract

Parkinson’s disease (PD) involves significant non-motor symptoms (NMS) linked to glutamate dysregulation.

Objective:: This review evaluates the efficacy of N-methyl-D-aspartate (NMDA) receptor antagonists (memantine and amantadine) for treating NMS.

Methods:: A search was conducted in the databases PubMed and Cochrane Library (January 2000–September 2025) for controlled trials focusing on NMS in idiopathic PD. Two reviewers assessed bias using Cochrane RoB 2.

Results:: Of 529 records, ten studies were included. Most exhibited a high risk of bias and heterogeneity. Memantine results were mixed: improvements in attention and behavioral symptoms were observed in PD dementia, but no benefit or worsened memory occurred in mild cognitive impairment. Memantine was beneficial for REM sleep behavior disorder. Extended-release amantadine improved sleepiness and mood but increased hallucinations and cognitive impairment.

Conclusion:: Evidence is limited by methodological flaws. While memantine offers selective benefits for PD dementia, amantadine carries notable cognitive risks. High-quality trials are essential to clarify therapeutic roles.

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BibTeX RIS

BibTeX

@article{orlino2026efficacy,
  title = {{The efficacy of NMDA receptor antagonists in neuropsychiatric and non-motor symptoms of Parkinson’s disease: a systematic review}},
  author = {Jan Arel Solomon Orlino and Ma. Lourdes Corrales-Joson},
  journal = {Dementia \& Neuropsychologia},
  year = {2026},
  month = nov,
  doi = {10.1590/1980-5764-dn-2026-0496},
  url = {https://doi.org/10.1590/1980-5764-dn-2026-0496},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - The efficacy of NMDA receptor antagonists in neuropsychiatric and non-motor symptoms of Parkinson’s disease: a systematic review
AU  - Jan Arel Solomon Orlino
AU  - Ma. Lourdes Corrales-Joson
PY  - 2026
DA  - 2026/11/02
JO  - Dementia & Neuropsychologia
DO  - 10.1590/1980-5764-dn-2026-0496
UR  - https://doi.org/10.1590/1980-5764-dn-2026-0496
AB  - Parkinson’s disease (PD) involves significant non-motor symptoms (NMS) linked to glutamate dysregulation.  Objective:: This review evaluates the efficacy of N-methyl-D-aspartate (NMDA) receptor antagonists (memantine and amantadine) for treating NMS.  Methods:: A search was conducted in the databases PubMed and Cochrane Library (January 2000–September 2025) for controlled trials focusing on NMS in idiopathic PD. Two reviewers assessed bias using Cochrane RoB 2.  Results:: Of 529 records, ten studies were included. Most exhibited a high risk of bias and heterogeneity. Memantine results were mixed: improvements in attention and behavioral symptoms were observed in PD dementia, but no benefit or worsened memory occurred in mild cognitive impairment. Memantine was beneficial for REM sleep behavior disorder. Extended-release amantadine improved sleepiness and mood but increased hallucinations and cognitive impairment.  Conclusion:: Evidence is limited by methodological flaws. While memantine offers selective benefits for PD dementia, amantadine carries notable cognitive risks. High-quality trials are essential to clarify therapeutic roles.
SN  - 1980-5764
SN  - 2764-4863
ER  -

Abstract

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