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Review

Pharmacological management of dementia with Lewy bodies with a focus on zonisamide for treating parkinsonism

ORCID Icon, ORCID Icon, &
Pages 325-337 | Received 17 Feb 2020, Accepted 21 Sep 2020, Published online: 06 Oct 2020

References

  • Walker Z, Possin KL, Boeve BF, et al. Lewy body dementias. Lancet. 2015;386:1683–1697.
  • Vann Jones SA, O’Brien JT. The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychol Med. 2014;44:673–683.
  • McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the dementia with Lewy bodies consortium. Neurology. 2017;89:88–100.
  • Hogan DB, Fiest KM, Roberts JI, et al. The prevalence and incidence of dementia with Lewy bodies: a systematic review. Can J Neurol Sci. 2016;43:S83–95.
  • Aarsland D, Zaccai J, Brayne C. A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord. 2005;20:1255–1263.
  • Hely MA, Reid WG, Adena MA, et al. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23:837–844.
  • Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord. 2007;22:1689–1707.
  • Byrne EJ, Lennox G, Godwin-Austen RB, et al. Dementia associated with cortical Lewy bodies: proposed clinical diagnostic criteria. Dementia. 1991;2:283–284.
  • Barnes J, Dickerson BC, Frost C, et al. van der Flier WM. Alzheimer’s disease first symptoms are age dependent: evidence from the NACC dataset. Alzheimers Dement. 2015;11:1349–1357.
  • Savica R, Grossardt BR, Bower JH, et al. Incidence of dementia with Lewy bodies and Parkinson disease dementia. JAMA Neurol. 2013;70:1396–1402.
  • McKeith I, O’Brien J, Walker Z, et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol. 2007;6:305–313.
  • Yoshita M, Arai H, Arai H, et al. Diagnostic accuracy of I-123-meta-iodobenzylguanidine myocardial scintigraphy in dementia with Lewy bodies: a multicenter study. PLoS One. 2015;10:e0120540.
  • Postuma RB, Gagnon JF, Vendette M, et al. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology. 2009;72:1296–1300.
  • Burton EJ, Barber R, Mukaetova-Ladinska EB, et al. Medial temporal lobe atrophy on MRI differentiates Alzheimer’s disease from dementia with Lewy bodies and vascular cognitive impairment: a prospective study with pathological verification of diagnosis. Brain. 2009;132:195–203.
  • Lobotesis K, Fenwick JD, Phipps A, et al. Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD. Neurology. 2001;56(5):643–649. .
  • O’Brien JT, Firbank MJ, Davison C, et al. 18F-FDG PET and perfusion SPECT in the diagnosis of Alzheimer and Lewy body dementias. J Nucl Med. 2014;55(12):1959–1965. .
  • Lim SM, Katsifis A, Villemagne VL, et al. The 18F-FDG PET cingulate island sign and comparison to 123I-beta-CIT SPECT for diagnosis of dementia with Lewy bodies. J Nucl Med. 2009;50:1638–1645.
  • Bonanni L, Thomas A, Tiraboschi P, et al. Onofrj M EEG comparisons in early Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease with dementia patients with a 2-year follow-up. Brain. 2008;131:690–705.
  • Guerreiro R, Escott-Price V, Darwent L, et al. Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson’s and Alzheimer’s diseases. Neurobiol Aging. 2016;38:214.e7-214.e10.
  • Guerreiro R, Ross OA, Kun-Rodrigues C, et al. Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol. 2018;17:64–74.
  • Mata IF, Leverenz JB, Weintraub D, et al. APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease. JAMA Neurol. 2014;71:1405–1412.
  • Johnson J, Hague SM, Hanson M, et al. SNCA multiplication is not a common cause of Parkinson disease or dementia with Lewy bodies. Neurology. 2004;63:554–556.
  • Ferman TJ, Smith GE, Kantarci K, et al. Nonamnestic mild cognitive impairment progresses to dementia with Lewy bodies. Neurology. 2013;81:2032–2038.
  • McKeith I, Taylor JP, Thomas A, et al. Revisiting DLB diagnosis: a consideration of prodromal DLB and of the diagnostic overlap with Alzheimer disease. J Geriatr Psychiatry Neurol. 2016;29:249–253.
  • McKeith IG, Ferman TJ, Thomas AJ, et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology. 2020;94:743–755.
  • Montine TJ, Phelps CH, Beach TG, et al. National institute on aging-Alzheimer’s association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach. Acta Neuropathol. 2012;123:1–11.
  • Irwin DJ, White MT, Toledo JB, et al. Neuropathologic substrates of Parkinson disease dementia. Ann Neurol. 2012;72:587–598.
  • Colom-Cadena M, Gelpi E, Charif S, et al. Confluence of alpha-synuclein, tau, and beta-amyloid pathologies in dementia with Lewy bodies. J Neuropathol Exp Neurol. 2013;72:1203–1212.
  • Del Tredici K, Braak H. Dysfunction of the locus coeruleus-norepinephrine system and related circuitry in Parkinson’s disease-related dementia. J Neurol Neurosurg Psychiatry. 2013;84:774–783.
  • Howlett DR, Whitfield D, Johnson M, et al. Regional multiple pathology scores are associated with cognitive decline in Lewy body dementias. Brain Pathol. 2015;25:401–408.
  • Hepp DH, Vergoossen DL, Huisman E, et al. Distribution and load of amyloid-beta pathology in Parkinson disease and dementia with Lewy bodies. J Neuropathol Exp Neurol. 2016;75:936–945.
  • Jellinger KA, Korczyn AD. Are dementia with Lewy bodies and Parkinson’s disease dementia the same disease? BMC Med. 2018;16:34.
  • Kosaka K, Oyanagi S, Matsushita M, et al. Presenile dementia with Alzheimer-, Pick- and Lewy body changes. Acta Neuropathol. 1976;36:221–233.
  • Kosaka K, Manabe Y. The first autopsied case of diffuse Lewy body disease (DLBD): re-examination by recent immunostaining methods: the 50th Anniversary of Japanese Society of Neuropathology. Neuropathology. 2010;30:458–642.
  • Hamilton RL. Lewy bodies in Alzheimer’s disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol. 2000;10:378–384.
  • Uchikado H, Lin WL, DeLucia MW, et al. Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy. J Neuropathol Exp Neurol. 2006;65:685–697.
  • Leverenz JB, Fishel MA, Peskind ER, et al. Lewy body pathology in familial Alzheimer disease: evidence for disease- and mutation-specific pathologic phenotype. Arch Neurol. 2006;63:370–376.
  • Lippa CF, Duda JE, Grossman M, et al. DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology. 2007;68:812–819.
  • Compta Y, Parkkinen L, O’Sullivan SS, et al. Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important? Brain. 2011;134:1493–1505.
  • Jellinger KA. Neurobiology of cognitive impairment in Parkinson’s disease. Expert Rev Neurother. 2012;12:1451–1466.
  • Irwin DJ, Lee VM, Trojanowski JQ. Parkinson’s disease dementia: convergence of alpha-synuclein, tau and amyloid-beta pathologies. Nat Rev Neurosci. 2013;14:626–636.
  • Braak H, Del Tredici K, Rüb U, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24:197–211.
  • Schneider JA, Arvanitakis Z, Yu L, et al. Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies. Brain. 2012;135:3005–3014.
  • Rufmann C, Calboli FC, Bravi I, et al. Cortical Lewy bodies and Abeta burden are associated with prevalence and timing of dementia in Lewy body diseases. Neuropathol Appl Neurobiol. 2016;42:436–450.
  • Deramecourt V, Bombois S, Maurage CA, et al. Biochemical staging of synucleinopathy and amyloid deposition in dementia with Lewy bodies. J Neuropathol Exp Neurol. 2006;65:278–288.
  • Braak H, Bohl JR, Muller CM, et al. the staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Mov Disord. 2005;2006(21):2042–2051.
  • Jellinger KA. Significance of brain lesions in Parkinson disease dementia and Lewy body dementia. Front Neurol Neurosci. 2009;24:114–125.
  • Barker RA, Williams-Gray CH. Review: the spectrum of clinical features seen with alpha synuclein pathology. Neuropathol Appl Neurobiol. 2016;(2016)(42):6–19.
  • Beach TG, Adler CH, Lue L, et al. Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol. 2009;117:613–634.
  • Fujishiro H, Tsuboi Y, Lin W-L, et al. Co-localization of tau and alpha-synuclein in the olfactory bulb in Alzheimer’s disease with amygdala Lewy bodies. Acta Neuropathol. 2008;116:17–24.
  • Dickson DW, Braak H, Duda JE, et al. Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria. Lancet Neurol. 2009;8:1150–1157.
  • Mueller C, Ballard C, Corbett A, et al. The prognosis of dementia with Lewy bodies. Lancet Neurol. 2017;16:390–398.
  • Panza F, Lozupone M, Logroscino G, et al. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat Rev Neurol. 2019;15:73–88.
  • Aarsland D, Ballard C, Rongve A, et al. Clinical trials of dementia with Lewy bodies and Parkinson’s disease dementia. Curr Neurol Neurosci Rep. 2012;12:492–501.
  • Diagnosis TB. Management of cognitive and behavioral changes in dementia with Lewy bodies. Curr Treat Options Neurol. 2017;9;19:42.
  • Palermo G, Ceravolo R, Bonuccelli U. Advances in the pharmacotherapeutic management of dementia with Lewy bodies. Expert Opin Pharmacother. 2018;19:1643–1653.
  • Hershey LA, Coleman-Jackson R. Pharmacological management of dementia with Lewy Bodies. Drugs Aging. 2019;36:309–319.
  • Taylor JP, McKeith IG, Burn DJ, et al. New evidence on the management of Lewy body dementia. Lancet Neurol. 2019;19:157–169.
  • Lee G, Cummings J, Decourt B, et al. Clinical drug development for dementia with Lewy bodies: past and present. Expert Opin Investig Drugs. 2019;28:951–965.
  • Eisai C ARICEPT approved in Japan as treatment for dementia with Lewy bodies. 2014. https://www.eisai.com/news/news201452.html. Last accessed: 2020 Sept 18.
  • O’Brien JT, Burns A. Clinical practice with anti-dementia drugs: a revised (second) consensus statement from the British association for psychopharmacology. J Psychopharmacol. 2011;25:997–1019.
  • Boot BP. Comprehensive treatment of dementia with Lewy bodies. Alzheimers Res Ther. 2015;7:45.
  • Tiraboschi P, Hansen LA, Alford M, et al. Cholinergic dysfunction in diseases with Lewy bodies. Neurology. 2000;54(2):407–411.
  • Grothe MJ, Schuster C, Bauer F, et al. Atrophy of the cholinergic basal forebrain in dementia with Lewy bodies and Alzheimer’s disease dementia. J Neurol. 2014;261:1939–1948.
  • Marquie M, Locascio JJ, Rentz DM, et al. Striatal and extrastriatal dopamine transporter levels relate to cognition in Lewy body diseases: an (11)C altropane positron emission tomography study. Alzheimers Res Ther. 2014;6(5–8):52.
  • McKeith I, DelSer T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomized, double-blind, placebo-controlled international study. Lancet. 2000;356:2031–2036.
  • Edwards K, Royall D, Hershey L, et al. Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a 24-week open-label study. Dement Geriatr Cogn Disord. 2007;23:401–405.
  • Mori E, Ikeda M, Kosaka K. Donepezil-DLB study investigators. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial. Ann Neurol. 2012;72:41–52.
  • Ikeda M, Mori E, Matsuo K, et al. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled, confirmatory phase III trial. Alzheimers Res Ther. 2015;7:4.
  • Wang HF, Yu JT, Tang SW, et al. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J Neurol Neurosurg Psychiatry. 2015;86:135–143.
  • Stinton C, McKeith I, Taylor JP, et al. Pharmacological management of Lewy body dementia: a systematic review and meta-analysis. Am J Psychiatry. 2015;172:731–742.
  • Matsunaga S, Kishi T, Yasue I, et al. Cholinesterase inhibitors for Lewy body disorders: a meta-analysis. Int J Neuropsychopharmacol. 2015;19:1–15.
  • Warre R, Thiele S, Talwar S, et al. Altered function of glutaminergic cortico-striatal synapses causes output pathway abnormalities in a chronic model of parkinsonism. Neurobiol Dis. 2011;41:591–604.
  • Aarsland D, Ballard C, Walker Z, et al. Memantine in patients with Parkinson’s disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurol. 2009;8:613–618.
  • Emre M, Tsolaki M, Bonucelli U, et al. Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomized, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9:969–977.
  • Brennan L, Pantelyat A, Duda JE, et al. Memantine and cognition in Parkinson’s disease dementia/dementia with Lewy bodies: a metaanalysis. Mov Disord Clin Pract. 2015;3:161–167.
  • Matsunaga S, Kishi T, Iwata N. Memantine for Lewy body disorders: systematic review and meta-analysis. Am J Geriatr Psychiatry. 2015;23:373–383.
  • Meng YH, Wang PP, Song YX, et al. Cholinesterase inhibitors and memantine for Parkinson’s disease dementia and Lewy body dementia: A meta-analysis. Exp Ther Med. 2019;17:1611–1624.
  • Delli Pizzi S, Franciotti R, Tartaro A, et al. Structural alteration of the dorsal visual network in DLB patients with visual hallucinations: a cortical thickness MRI study. PLoS One. 2014;9:e86624.
  • Kurlan R, Cummings J, Raman R, et al. Quetiapine for agitation or psychosis in patients with dementia and parkinsonism. Neurology. 2007;68:1356–1363.
  • Cummings JL, Street J, Masterman D, et al. Efficacy of olanzapine in the treatment of psychosis in dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2002;13:67–73.
  • Zhang H, Wang L, Fan Y, et al. Atypical antipsychotics for Parkinson’s disease psychosis: a systematic review and meta-analysis. Neuropsychiatr Dis Treat. 2019;15:2137–2149.
  • Johnson M. Acadia pharmaceuticals presents positive top-line results from pivotal phase 3 HARMONY trial of pimavanserin in patients with dementia-related psychosis at 12th clinical trials on Alzheimer’s disease (CTAD) meeting. Acadia’s press release. December 4, 2019. Last accessed: 2020 Sept 18.
  • Fearnley JM, Lees AJ. Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain. 1991;114:2283–2301.
  • Lucetti C, Logi C, Del Dotto P, et al. Levodopa response in dementia with Lewy bodies: a 1-year follow-up study. Parkinsonism Relat Disord. 2010;16:522–526.
  • Molloy S, McKeith IG, O’Brien JT, et al. The role of levodopa in the management of dementia with Lewy bodies. J Neurol Neurosurg Psychiatry. 2005;76:1200–1203.
  • Goldman JG, Goetz CG, Brandabur M, et al. Effects of dopaminergic medications on psychosis and motor function in dementia with Lewy bodies. Mov Disord. 2008;23:2248–2250.
  • Factor SA, McDonald WM, Goldstein FC. The role of neurotransmitters in the development of Parkinson’s disease-related psychosis. Eur J Neurol. 2017;24:1244–1254.
  • Ray Chaudhuri K, Poewe W, Brooks D. Motor and nonmotor complications of levodopa: phenomenology, risk factors, and imaging features. Mov Disord. 2018;33:909–919.
  • Chan PC, Lee HH, Hong CT, et al. REM sleep behavior disorder (RBD) in dementia with Lewy bodies (DLB). Behav Neurol. 2018;2018:9421098.
  • Aurora RN, Zak RS, Maganti RK, et al. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med. 2010;6:85–95.
  • Lapid MI, Kuntz KM, Mason SS, et al. Efficacy, safety, and tolerability of armodafinil therapy for hypersomnia associated with dementia with Lewy bodies: a pilot study. Dement Geriatr Cogn Disord. 2017;43:269–280.
  • Prado E, Paholpak P, Ngo M, et al. Agitation and psychosis associated with dementia with Lewy bodies exacerbated by modafinil use. Am J Alzheimers Dis Other Demen. 2012;27:468–473.
  • De Pablo-Fernandez E, Tur C, Revesz T, et al. Association of autonomic dysfunction with disease progression and survival in Parkinson disease. JAMA Neurol. 2017;74: 970–976. Eur J Neurol. 2013; 20: 5–15.
  • Ferreira JJ, Katzenschlager R, Bloem BR, et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease.
  • Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease—an evidence-based medicine review. Mov Disord. 2019;34:180–198.
  • Kaufmann H, Freeman R, Biaggioni I, et al. Droxidopa for neurogenic orthostatic hypotension. A randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83:328–335.
  • Zangaglia R, Martignoni E, Glorioso M, et al. Macrogol for the treatment of constipation in Parkinson’s disease. A randomized placebo-controlled study. Mov Disord. 2007;22:1239–1244.
  • Ashraf W, Pfeiffer RF, Park F, et al. Constipation in Parkinson’s disease: objective assessment and response to psyllium. Mov Disord. 1997;12:946–951.
  • Zesiewicz TA, Evatt M, Vaughan CP, et al. Randomized, controlled pilot trial of solifenacin succinate for overactive bladder in Parkinson’s disease. Parkinsonism Relat Disord. 2015;21:514–520.
  • Peyronnet B, Vurture G, Palma JA, et al. Mirabegron in patients with Parkinson disease and overactive bladder symptoms: a retrospective cohort. Parkinsonism Relat Disord. 2018;57:22–26.
  • Jellinger KA. How can we best care for people with dementia with Lewy bodies pharmacologically? Expert Opin Pharmacother. 2020;21:513–515.
  • Price DL, Koike MA, Khan A, et al. The small molecule alpha-synuclein misfolding inhibitor, NPT200-11, produces multiple benefits in an animal model of Parkinson’s disease. Sci Rep. 2018;8:16165.
  • Bergstrom AL, Kallunki P, Fog K. Development of passive immunotherapies for synucleinopathies. Mov Disord. 2016;31:203–213.
  • Schneeberger A, Tierney L, Mandler M. Active immunization therapies for Parkinson’s disease and multiple system atrophy. Mov Disord. 2016;3:214–224.
  • Fernandez-Valle T, Gabilondo I, Gomez-Esteban JC. New therapeutic approaches to target alpha-synuclein in Parkinson’s disease: the role of immunotherapy. Int Rev Neurobiol. 2019;146:281–295.
  • Valera E, Masliah E. Combination therapies: the next logical step for the treatment of synucleinopathies? Mov Disord. 2016;31:225–234.
  • McNeill A, Magalhaes J, Shen C, et al. Ambroxol improves lysosomal biochemistry in glucocerebrocidase mutation-linked Parkinson disease cells. Brain. 2014;137:1481–1495.
  • Silveira CRA, MacKinley J, Coleman K, et al. Ambroxol as a novel disease-modifying treatment for Parkinson’s disease dementia: protocol for a single-centre, randomized, double-blind, placebo-controlled trial. BMC Neurol. 2019;19:20.
  • Nixon RA. The role of autophagy in neurodegenerative disease. Nat Med. 2013;19:983–997.
  • Hebron ML, Lonskaya I, Moussa CE. Nilotinib reverses loss of dopamine neurons and improve motor behavior via autophagic degradation of α-synuclein in Parkinson’s disease models. Hum Mol Genet. 2013;22:3315–3328.
  • Pagan F, Hebron M, Valadez E, et al. Nilotinib effects in Parkinson’s disease and dementia with Lewy bodies. J Parkinsons Dis. 2016;6:503–517.
  • Goldfine A, Faulkner R, Sadashivam V, et al. Results of a phase 1 dose-ranging trial, and design of a phase 2 trial, of K0706, a novel C-Abl tyrosine kinase inhibitor for Parkinson’s disease. Neurology. 2019;92:P2.8–047.
  • Scheltens P, Prins N, Lammertsma A, et al. An exploratory clinical study of p38α kinase inhibition in Alzheimer’s disease. Ann Clin Transl Neurol. 2018;5:464–473.
  • Nabavi SM, Talarek S, Listos J, et al. Phosphodiesterase inhibitors say NO to Alzheimer’s disease. Food Chem Toxicol. 2019;134:110822.
  • Hollerhage M, Moebius C, Melms J, et al. Protective efficacy of phosphodiesterase-1 inhibition against alpha-synuclein toxicity revealed by compound screening in LUHMES cells. Sci Rep. 2017;7:11469.
  • Ando M, Kotani S, Watanabe N. Preclinical characterization of E2027, a novel phosphodiesterase 9 inhibitor. Alzheimers Dement. 2017;13:P946.
  • Landry I, Lai RYK, Boyd P, et al. Phase 1 multiple ascending dose (MAD) study of phosphodiesterase-9 inhibitor E2027: confirmation of target engagement and selection of Phase 2 dose in dementia with Lewy bodies. Alzheimers Dement. 2018;14:P251.
  • Reimers A, Ljung H. An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy. Expert Opin Pharmacother. 2019;20:909–915.
  • Uto Y. 1, 2-benzisoxazole: a privileged structure with a potential for polypharmacology. Curr Pharm Des. 2016;22(21):3201–3211.
  • Leppik IE. Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004;13: S5–9. [Internet].
  • O’Neil MJ. The merck index - an encyclopedia of chemicals, drugs, and biologicals. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc; 2001. p. 1817.
  • Masuda Y, Ishizaki M, Zonisamide: SM. Pharmacology and Clinical Efficacy in Epilepsy. CNS Drug Rev. 1998;4:341–360.
  • Zonegran EMA. EPAR product information. Last accessed:. 2020 September 18. Available from: https://www.ema.europa.eu/documents/productinformation/zonegran-epar-product-information_en.pdf.
  • FDA label database: zonegran. Last accessed: september 18, 2020. Available from: http://dailymed.nlm.nih.gov/dailymed/downloadpdffile.cfm?setId=d12de43e-3ac3-4335-bc85-70d7366a91eb.
  • Dainippon Sumitomo Pharma. Notice of launching of a new Parkinson’s disease drug “TRERIEF®. 2009. Last accessed: 2020 Sept 18. Available from: https://www.ds-pharma.com/ir/news/pdf/ene20090313.pdf
  • Murata M, Hasegawa K, Kanazawa I. the Japan Zonisamide study group. randomized, double-blind study of zonisamide with placebo in advanced Parkinson’s disease. Mov Disord. 2004;19:S198.
  • Murata M, Hasegawa K, Kanazawa I. The Japan Zonisamide on PD Study Group. Zonisamide improves motor function in Parkinson disease: A randomized, double-blind study. Neurology. 2007;68:45–50.
  • Murata M, Hasegawa K, Kanazawa I, et al. The Japan Zonisamide on PD study group. Zonisamide improves wearing-off in Parkinson’s disease: a randomized, double-blind study. Mov Disord. 2015;30:1343–1350.
  • Murata M, Hasegawa K, Kanazawa I, et al. The Zonisamide PD study group. Randomized placebo-controlled trial of zonisamide in patients with Parkinson’s disease. Neurol Clin Neurosci. 2016;4:10–15.
  • Murata M, Odawara T, Hasegawa K, et al. Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized, double-blind phase 2 study. Neurology. 2018;90:e664–e672.
  • Murata M, Odawara T, Hasegawa K, et al. Effect of zonisamide on parkinsonism in patients with dementia with Lewy bodies: A phase 3 randomized clinical trial. Parkinsonism Relat Disord. 2019; pii: S1353-8020(19)30524-3. doi: 10.1016/j.parkreldis.2019.12.005 [ Epub ahead of print.
  • Dainippon Sumitomo Pharma. Sumitomo Dainippon pharma obtains approval in Japan for TRERIEF®, a therapeutic agent for Parkinson’s disease, for an additional indication of parkinsonism in dementia with Lewy bodies. 2018. Last accessed: 2020 Sept 18. Available from: https://www.ds-pharma.com/ir/news/pdf/ene20180702.pdf
  • Yamamura S, Ohoyama K, Nagase H, et al. Zonisamide enhances delta receptor-associated neurotransmitter release in striato-pallidal pathway. Neuropharmacology. 2009;57:322–331.
  • Okada M, Kaneko S, Hirano T, et al. Effects of zonisamide on dopaminergic system. Epilepsy Res. 1995;22:193–205.
  • Sonsalla PK, Wong LY, Winnik B, et al. The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010;221:329–334.
  • Murata M. Novel therapeutic effects of the anti-convulsant, zonisamide, on Parkinson’s Disease. Curr Pharm Des. 2004;10:687–693.
  • Suzuki S, Kawakami K, Nishimura S, et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 1992;12:21–27.
  • Kito M, Maehara M, Watanabe K. Mechanisms of T-type calcium channel blockade by zonisamide. Seizure. 1996;5:115–119.
  • Ueda Y, Doi T, Tokumaru J, et al. Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures. Brain Res Mol Brain Res. 2003;116:1–6.
  • Uemura MT, Asano T, Hikawa R, et al. Zonisamide inhibits monoamine oxidase and enhances motor performance and social activity. Neurosci Res. 2017;124:25–32.
  • Kumar B, Medhi B, Modi M, et al. A mechanistic approach to explore the neuroprotective potential of zonisamide in seizures. Inflammopharmacology. 2018;26:1125–1131.
  • Ghaemi SN, Zablotsky B, Filkowski MM, et al. An open prospective study of zonisamide in acute bipolar depression. J Clin Psychopharmacol. 2006;26:385–388.
  • Ghaemi SN, Shirzadi AA, Klugman J, et al. Is adjunctive open-label zonisamide effective for bipolar disorder? J Affect Disord. 2008;105:311–314.
  • Gadde KM, Franciscy DM, Wagner HR II, et al. Zonisamide for weight loss in obese adults a randomized controlled trial. JAMA. 2003;289:1820–1825.
  • McElroy SL, Kotwal R, Guerdijkova AI, et al. Zonisamide in the treatment of binge eating disorder with obesity: a randomized controlled trial. J Clin Psychiatry. 2006;67:1897–1906.
  • Chung JY, Kim MW, Kim M. Efficacy of zonisamide in migraineurs with nonresponse to topiramate. Biomed Res Int. 2014;2014:891348.
  • Knapp CM, Ciraulo DA, Sarid-Segal O, et al. Zonisamide, topiramate and levetiracetam: efficacy and neuropsychological effects in alcohol use disorders. J Clin Psychopharmacol. 2015;35:34–42.
  • Kinrys G, Vasconcelos E Sa D, Nery F. Adjunctive zonisamide for treatment refractory anxiety. Int J Clin Pract. 2007;61:1050–1053.
  • Zupo R, Castellana F, Bortone I, et al. Nutritional domains in frailty tools: working towards an operational definition of nutritional frailty. Ageing Res Rev. 2020;101148. Online ahead of print. doi:10.1016/j.arr.2020.101148
  • Ohtahara S, Yamatogi Y. Safety of zonisamide therapy: prospective follow-up survey. Seizure. 2004;13:50–55.
  • Leppik IE. Zonisamide. Epilepsia. 1999;40(Suppl 5):S23–29.
  • Sills G, Brodie M. Pharmacokinetics and drug interactions with zonisamide. Epilepsia. 2007;48:435–441.
  • Janković SM. Evaluation of zonisamide for the treatment of focal epilepsy: A review of pharmacokinetics, clinical efficacy and adverse effects. Expert Opin Drug Metab Toxicol. 2020;16:169–177.
  • Mimaki T. Clinical pharmacology and therapeutic drug monitoring of zonisamide. Ther Drug Monit. 1998;20:593–597.
  • Verdier M-C, Bentué-Ferrer D, Tribut O; le groupe Suivi Thérapeutique Pharmacologique de la Société Française de Pharmacologie et de Thérapeutique. [Therapeutic drug monitoring of zonisamide]. Therapie. 2010;65:29–34.
  • Saruwatari J, Ishitsu T, Nakagawa K. Update on the genetic polymorphisms of drug-metabolizing enzymes in antiepileptic drug therapy. Pharm Basel Switz. 2010;3:2709–2732.
  • Ragueneau-Majlessi I, Levy RH, Bergen D, et al. Carbamazepine pharmacokinetics are not affected by zonisamide: in vitro mechanistic study and in vivo clinical study in epileptic patients. Epilepsy Res. 2004;62:1–11.
  • Patsalos PN. Drug interactions with the newer antiepileptic drugs (AEDs)–part 1: pharmacokinetic and pharmacodynamic interactions between AEDs. Clin Pharmacokinet. 2013;52:927–966.
  • Perucca E, Bialer M. The clinical pharmacokinetics of the newer antiepileptic drugs. Focus on Topiramate, Zonisamide and Tiagabine. Clin Pharmacokinet. 1996;31:29–46.
  • Okada Y, Seo T, Ishitsu T, et al. Population estimation regarding the effects of cytochrome P450 2C19 and 3A5 polymorphisms on zonisamide clearance. Ther Drug Monit. 2008;30:540–543.
  • Lozupone M, Panza F, Stella E, et al. Pharmacogenetics of neurological and psychiatric diseases at older age: has the time come? Expert Opin Drug Metab Toxicol. 2017;13:259–277.
  • Rock DM, Macdonald RL, Taylor CP. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 1989;3:138–143.
  • Yoshida S, Okada M, Zhu G, et al. Effects of zonisamide on neurotransmitter exocytosis associated with ryanodine receptors. Epilepsy Res. 2005;67:153–162.
  • Gluck MR, Santana LA, Granson H, et al. Novel dopamine releasing response of an anti-convulsant agent with possible anti-Parkinson’s activity. J Neural Transm. 2004;111:713–724.
  • Okada M, Kaneko S, Hirano T, et al. Effects of zonisamide on extracellular levels of monoamine and its metabolites, and on Ca2+ dependent dopamine release. Epilepsy Res. 1992;13:113–119.
  • Farooq MU, Moore PW, Bhatt A, et al. Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008;8:968–975.
  • Park SP, Kim SY, Hwang YH, et al. Long-term efficacy and safety of zonisamide monotherapy in epilepsy patients. J Clin Neurol. 2007;3:175–180.
  • Pietrzak B, Zwierzyńska E, Krupa A. A pharmaco-EEG-based assessment of the interaction between ethanol and zonisamide. Alcohol Alcohol. 2014;49:505–514.
  • Krupa-Burtnik A, Zwierzyńska E, Pietrzak B. The effect of Zonisamide on memory processes - a preclinical study. Epilepsy Behav. 2020;102:106659.
  • Owen AJ, Ijaz S, Miyashita H, et al. Zonisamide as a neuroprotective agent in an adult gerbil model of global forebrain ischemia: a histological, in vivo microdialysis and behavioral study. Brain Res. 1997;770:115–122.
  • Ono K, Takasaki J, Takahashi R, et al. Effects of antiparkinsonian agents on β-Amyloid and α-Synuclein oligomer formation in vitro. J Neurosci Res. 2013;91:1371–1381.
  • Odawara T, Shiozaki K, Togo T, et al. Administration of zonisamide in three cases of dementia with Lewy bodies. Psychiatry Clin Neurosci. 2010;64:327–329.
  • Sato S, Mizukami K, Asada T. Successful treatment of extrapyramidal and psychotic symptoms with zonisamide in a patient with dementia with Lewy bodies. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:1130–1131.
  • Taguchi Y, Takashima S, Tanaka K. Improvement in parkinsonism with zonisamide treatment in a patient with dementia with Lewy bodies. J Neurol Stroke. 2014;1:00017.
  • Kramberger MG, Auestad B, Garcia-Ptacek S, et al. Long-term cognitive decline in dementia with Lewy bodies in a large multicenter, international cohort. J Alzheimers Dis. 2017;57:787–795.
  • Rongve A, Soennesyn H, Skogseth R, et al. Cognitive decline in dementia with Lewy bodies: a 5-year prospective cohort study. BMJ Open. 2016;6:e010357.
  • Nelson PT, Kryscio RJ, Jicha GA, et al. Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies. Neurology. 2009;73:1127–1133.
  • Bernard BA, Carns D, Stebbins GT, et al. Relationship of Movement Disorders Society-Unified Parkinson’s Disease Rating Scale Nonmotor Symptoms to Cognitive Functioning in Patients with Parkinson’s Disease. Mov Disord Clin Pract. 2020;7:279–283.
  • Matsunaga S, Kishi T, Iwata N. Combination therapy with zonisamide and antiparkinson drugs for Parkinson’s disease: a meta-analysis. J Alzheimers Dis. 2017;56:1229–1239.
  • Hershey LA, Irwin DJ. Zonisamide for DLB parkinsonism: an old drug used in a new context. Neurology. 2018;90:349–350.
  • Tahami Monfared AA, Meier G, Perry R, et al. Burden of disease and current management of dementia with Lewy bodies: A literature review. Neurol Ther. 2019;8:289–305.
  • McKeith I, Aarsland D, Friedhoff L, et al. HEADWAY-DLB: a multinational study evaluating the safety and efficacy of intepirdine (RVT-101) in dementia with Lewy bodies. Alzheimers Dement. 2017;13:P936.7.
  • Axovant Sciences Ltd. Press Release: axovant announces negative results for interpirdine in phase 2b HEADWAY and pilot phase 2 gait and balance studies; positive trends in efficacy seen in pilot phase 2 nelotanserin study; January 8, 2018. Last accessed: 2020 Sept 18. Available from: http://investors.axovant.com/newsreleases/news-release-details/axovant-announces-negative-results-intepirdinephase-2b-headway.
  • Fields CR, Bengoa-Vergniory N, Wade-Martins R. Targeting alphasynuclein as a therapy for Parkinson’s disease. Front Mol Neurosci. 2019;12:299.
  • Takahashi S, Mizukami K, Yasuno F, et al. Depression associated with dementia with Lewy bodies (dementia with Lewy bodies) and the effect of somatotherapy. Psychogeriatrics. 2009;9:56–61.
  • Elder GJ, Ashcroft J, da Silva Morgan K, et al. Transcranial direct current stimulation in Parkinson’s disease dementia: a randomized double-blind crossover trial. Brain Stimul. 2017;10:1150–1151.
  • Elder GJ, Colloby SJ, Firbank MJ, et al. Consecutive sessions of transcranial direct current stimulation do not remediate visual hallucinations in Lewy body dementia: a randomised controlled trial. Alzheimers Res Ther. 2019;11:9.
  • Gratwicke J, Zrinzo L, Kahan J, et al. Bilateral deep brain stimulation of the nucleus basalis of meynert for Parkinson disease dementia: a randomized clinical trial. JAMA Neurol. 2018;75:169–178.
  • Connors MH, Quinto L, McKeith I, et al. Non-pharmacological interventions for Lewy body dementia: a systematic review. Psychol Med. 2018;48:1749–1758.
  • Mandler M, Rockenstein E, Overk C, et al. Effects of single and combined immunotherapy approach targeting amyloid beta protein and alpha-synuclein in a dementia with Lewy bodies-like model. Alzheimers Dement. 2019;15:1133–1148.
  • Peterson B, Armstrong M, Galasko D, et al. Lewy body dementia association’s research centers of excellence program: inaugural meeting proceedings. Alzheimers Res Ther. 2019;11:23.

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