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      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

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      The Application of Zonisamide to Patients Suffering from Dementia with Lewy Bodies: Emerging Clinical Data

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          Abstract

          Zonisamide is an anti-epileptic medication with multiple mechanisms of action and a favorable safety profile. Zonisamide may interact with Lewy body dementia pathophysiology through a mechanism unrelated to its original indication. Zonisamide has shown efficacy as adjunct therapy for the management of motor symptoms in patients with Parkinson’s disease (PD). Given that dementia with Lewy bodies (DLB) and PD are considered subtypes of a Lewy body disease spectrum, zonisamide was investigated for the treatment of parkinsonism in DLB. Phase II and phase III clinical trials were conducted in patients with DLB in Japan. In both studies, participants were randomized to receive 12 weeks of zonisamide 25 or 50 mg/day or placebo. Zonisamide significantly improved the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) without affecting the Mini-Mental State Examination (MMSE) or Neuropsychiatry Inventory-10 (NPI-10) scores at week 12. In 2018, zonisamide received Japanese regulatory approval for the additional indication of parkinsonism in DLB. This review discusses the emerging clinical data on zonisamide in the field of DLB.

          Most cited references34

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          Diagnosis and management of dementia with Lewy bodies

          Ian G. McKeith, Bradley F Boeve, Dennis W. Dickson … (2017)
          The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.
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            The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia

            J L Cummings, M. Mega, K. Gray … (1994)
            Neurology, 44(12), 2308-2308
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              International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease.

              Susan Fox, Regina Katzenschlager, Shen-Yang Lim … (2018)
              The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD).
              Article 0 comments Cited 265 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): dddt
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 03 May 2021
                Publication date Collection: 2021
                Volume: 15
                Pages: 1811-1817
                Affiliations
                [1 ]Cleveland Clinic Lerner College of Medicine of Case Western Reserve University , Cleveland, OH, USA
                [2 ]Lou Ruvo Center for Brain Health, Cleveland Clinic , Cleveland, OH, USA
                Author notes
                Correspondence: Babak Tousi Lou Ruvo Center for Brain Health, U-10, Cleveland Clinic , 9500 Euclid Ave, Cleveland, OH, 44195, USATel +1 216 237 6400 Email batous@ccf.org
                Article
                Publisher ID: 240865
                DOI: 10.2147/DDDT.S240865
                PMC ID: 8106402
                SO-VID: 2e81df8f-6903-453c-af82-3f3b879e5584
                Copyright statement: © 2021 Tousi and Leverenz.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 09 January 2021
                Date accepted : 08 April 2021
                Page count
                Figures: 0, Tables: 2, References: 38, Pages: 7
                Categories
                Subject: Review

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: dementia with lewy bodies,zonisamide,clinical trial,parkinsonism
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: dementia with lewy bodies, zonisamide, clinical trial, parkinsonism

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