Memantine as an Adjunctive Treatment for Residual Anxiety and Agitation in Early Parkinson's Disease With Depression:...

Non-motor psychiatric symptoms, including anxiety, agitation, and irritability, are common in Parkinson's disease (PD) and may persist despite antidepressant treatment. While monoaminergic dysfunction has traditionally been emphasized, accumulating evidence suggests that glutamatergic dysregulation, particularly involving N-methyl-D-aspartate (NMDA) receptors, may contribute to these symptoms. However, clinical evidence supporting NMDA receptor modulation in early-stage PD without dementia remains limited.

We report the case of a 65-year-old woman with early-stage PD (Hoehn and Yahr stage I) who developed a severe depressive episode accompanied by prominent anxiety and agitation. Treatment with vortioxetine resulted in partial improvement of depressive symptoms, as reflected by a gradual reduction in the Montgomery-Åsberg Depression Rating Scale score; however, significant anxiety, agitation, and irritability persisted despite adjunctive brexpiprazole, necessitating behavioral restriction. Given the limited response and the clinical characteristics of the residual symptoms, low-dose memantine (5 mg/day) was introduced as an off-label adjunctive therapy after obtaining informed consent. Approximately 10 days after memantine initiation, anxiety and agitation markedly improved, allowing discontinuation of behavioral restriction. Motor symptoms and cognitive function remained stable throughout treatment and follow-up.

This case suggests that NMDA receptor antagonism with low-dose memantine may be a well-tolerated adjunctive option for residual anxiety and agitation in early-stage PD without dementia when conventional antidepressant treatment is insufficient. Although interpretation is limited by the single-case design and concomitant medications, the findings support further investigation of glutamatergic mechanisms and NMDA receptor modulation in the management of non-motor psychiatric symptoms in PD.