{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T11:49:22Z","timestamp":1782388162431,"version":"3.54.5"},"reference-count":10,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropsychopharm Rep"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non\u2010motor 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\u2010methyl\u2010D\u2010aspartate (NMDA) receptors, may contribute to these symptoms. However, clinical evidence supporting NMDA receptor modulation in early\u2010stage PD without dementia remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentation<\/jats:title>\n                    <jats:p>We report the case of a 65\u2010year\u2010old woman with early\u2010stage 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\u2013\u00c5sberg 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\u2010dose memantine (5\u2009mg\/day) was introduced as an off\u2010label adjunctive therapy after obtaining informed consent. Approximately 10\u2009days after memantine initiation, anxiety and agitation markedly improved, allowing discontinuation of behavioral restriction. Motor symptoms and cognitive function remained stable throughout treatment and follow\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This case suggests that\n                      <jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>\n                      receptor antagonism with low\u2010dose memantine may be a well\u2010tolerated adjunctive option for residual anxiety and agitation in early\u2010stage\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      without dementia when conventional antidepressant treatment is insufficient. Although interpretation is limited by the single\u2010case design and concomitant medications, the findings support further investigation of glutamatergic mechanisms and\n                      <jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>\n                      receptor modulation in the management of non\u2010motor psychiatric symptoms in\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/npr2.70129","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:55:39Z","timestamp":1778741739000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Memantine as an Adjunctive Treatment for Residual Anxiety and Agitation in Early Parkinson's Disease With Depression: A Case Report"],"prefix":"10.1002","volume":"46","author":[{"given":"Takaumi","family":"Haga","sequence":"first","affiliation":[{"name":"Department of Neuropsychiatry, School of Medicine Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9054-1692","authenticated-orcid":false,"given":"Yuhei","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, School of Medicine Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3773-6778","authenticated-orcid":false,"given":"Nozomu","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, School of Medicine Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8430-9030","authenticated-orcid":false,"given":"Yuhei","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, School of Medicine Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiro","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, School of Medicine Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2133-5809","authenticated-orcid":false,"given":"Itaru","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, School of Medicine Fukushima Medical University  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci12111466"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina59081454"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-018-0162-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.938"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70146-2"},{"key":"e_1_2_10_7_1","first-page":"1339","article-title":"Development of the Revised Version of Hasegawa's Dementia Scale (HDS\u2010R)","volume":"2","author":"Katoh S.","year":"1991","journal-title":"Japanese Journal of Geriatric Psychiatry"},{"key":"e_1_2_10_8_1","first-page":"20","article-title":"The Revised Hasegawa's Dementia Scale (HDS\u2010R)\u2010Evaluation of Its Usefulness as a Screening Test for 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