Login Register Cart 0
Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Systematic Review Article

A New Hope in Alzheimer's Disease Psychosis: Pimavanserin

Author(s): Faruk Kurhan* and Mustafa Akın

Volume 20, Issue 6, 2023

Published on: 11 September, 2023

Page: [403 - 408] Pages: 6

DOI: 10.2174/1567205020666230825124922

Price: $65

conference banner
Abstract

Alzheimer's disease (AD) ranks first among the causes of dementia worldwide. AD can develop a psychotic manifest at a significant rate. AD prognosis worsens by added psychosis clinic. There is no treatment approved by the United States Food and Drug Administration (FDA) among antipsychotics for Alzheimer’s disease Psychosis (ADP). However, pimavanserine, an atypical antipsychotic, has been approved by the FDA for Parkinson's psychosis. It is predicted that pimavanserin, a new antipsychotic, will fill an important gap in this area. In clinical trials, it appears to be effective in the treatment of delusions and hallucinations at psychosis in both Parkinson's and AD. In this systematic review, we evaluated the analysis of current literature data on pimavanserin used in ADP. We searched the existing literature on clinical studies on pimavanserin therapy used in ADP. Data were determined by systematically searching PubMed, MEDLINE, EMBASE, and Google Scholar until December 2022. A total of 35 citations were found and uploaded on the Mendeley program. Abstracts and full texts of literature data were examined. Pimavanserin was observed, and satisfactory results were obtained in treating ADP. Pimavanserin has a unique mechanism of action. Pimavanserin, an atypical antipsychotic drug, has a low affinity for 5-HT2C receptors and has selective 5-HT2A reverse agonist/antagonist action. Pimavanserin has no clinically significant affinity for dopaminergic, histaminergic, muscarinic or adrenergic receptors. This agent may also achieve significant positive results in resistant psychosis treatments.

Keywords: Alzheimer´s disease, psychosis, antipsychotic, pimavanserin, dementia, Parkinson's psychosis.

« Previous Next »
[1]
Dementia: Number of people affected to triple in next 30 years. Available from:https://www.who.int/news/item/07-12-2017-dementia-number-of-people-affected-to-triple-in-next-30-years (Accessed on: 15 December 2022).
[2]
Haupt, M.; Kurz, A.; Jänner, M. A 2-year follow-up of behavioral and psychological symptoms in Alzheimer's disease. Dement. Geriatr. Cogn. Disord., 2000, 11(3), 147-152.
[3]
Ropacki, S.A.; Jeste, D.V. Epidemiology of and risk factors for psychosis of Alzheimer’s disease: A review of 55 studies published from 1990 to 2003. Am. J. Psychiatry, 2005, 162(11), 2022-2030.
[http://dx.doi.org/10.1176/appi.ajp.162.11.2022] [PMID: 16263838]
[4]
Zuidema, S.U.; Johansson, A.; Selbaek, G.; Murray, M.; Burns, A.; Ballard, C. A consensus guideline for antipsychotic drug use for dementia in care homes. Bridging the gap between scientific evidence and clinical practice. Int. Psychogeriatr., 2015, 27(11), 1849-59.
[http://dx.doi.org/10.1017/S1041610215000745] [PMID: 26062126]
[5]
Paulsen, J.; Salmon, D.; Thal, L.; Neurology, R.R. Incidence of and risk factors for hallucinations and delusions in patients with probable AD. Neurology, 2000, 54(10), 1965-71.
[http://dx.doi.org/10.1212/WNL.54.10.1965]
[6]
Bessey, L.J.; Walaszek, A. Management of behavioral and psychological symptoms of dementia. Curr. Psychiatry Rep., 2019, 21(8), 66.
[http://dx.doi.org/10.1007/s11920-019-1049-5] [PMID: 31264056]
[7]
Caraci, F.; Santagati, M.; Caruso, G.D.C. New antipsychotic drugs for the treatment of agitation and psychosis in Alzheimer's disease: Focus on brexpiprazole and pimavanserin. F1000Res., 2020, 9, F1000-686.
[http://dx.doi.org/10.12688/f1000research.22662.1]
[8]
Stern, Y.; Albert, M.; Brandt, J.; Jacobs, D.; Neurology, M.T. Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer's disease: Prospective analyses from the Predictors Study. Neurology, 1994, 44(12), 2300-7.
[http://dx.doi.org/10.1212/WNL.44.12.2300]
[9]
Peters, M.; Schwartz, S. Neuropsychiatric symptoms as predictors of progression to severe Alzheimer's dementia and death: The cache county study. Am. Assoc. Geria. Psych., 2014, 22(3)
[10]
Wang, X.; Zhou, Y.; He, S.; Ouyang, Z.; Feng, L.; Shen, Y.; Wu, X.; Sun, Y.; Wu, X.; Xu, Q. Obaculactone exerts a novel ameliorating effect on contact dermatitis through regulating T lymphocyte. Int. Immunopharmacol., 2015, 28(1), 1-9.
[http://dx.doi.org/10.1016/j.intimp.2015.05.015] [PMID: 26003846]
[11]
Murray, P.; Kumar, S. Psychosis in Alzheimer's disease. Biol. Psychiatry, 2014, 75(7), 542-552.
[12]
Ballard, C.; Banister, C.; Khan, Z.; Cummings, J.; Demos, G.; Coate, B. Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis: A phase 2, randomised, placebo-controlled, double-blind study. Lancet Neurol., 2018, 17(3), 213-222.
[13]
Schneider, L.S.; Frangakis, C.; Drye, L.T.; Devanand, D.P.; Marano, C.M.; Mintzer, J.; Mulsant, B.H.; Munro, C.A.; Newell, J.A.; Pawluczyk, S.; Pelton, G.; Pollock, B.G.; Porsteinsson, A.P.; Rabins, P.V.; Rein, L.; Rosenberg, P.B.; Shade, D.; Weintraub, D.; Yesavage, J.; Lyketsos, C.G. Heterogeneity of treatment response to citalopram for patients with Alzheimer’s disease with aggression or agitation: The citad randomized clinical trial. Am. J. Psychiatry, 2016, 173(5), 465-472.
[http://dx.doi.org/10.1176/appi.ajp.2015.15050648] [PMID: 26771737]
[14]
Coate, B.; Ballard, C.G.; Abler, V. Evaluation of the efficacy of pimavanserin in the treatment of agitation and aggression in patients with Alzheimer's disease psychosis: A post hoc analysis. Am. Assoc. Geria. Psych., 2020, 35(11), 1402-1408.
[15]
Cummings, J. The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer's disease. Am. Assoc. Geria. Psych., 1998, 6(2), S64-S78.
[16]
McIlroy, S.; David, C. Neurobiology and genetics of behavioral syndromes of Alzheimer's disease. Curr. Alzheimer Res., 2004, 1(2), 135-42.
[17]
Zubenko, G.; Moossy, J.; Martinez, A. Neuropathologic and neurochemical correlates of psychosis in primary dementia. Arch. Neurol., 1991, 48(6), 619-624.
[18]
Tekin, S.; Mega, M.S.; Masterman, D.M.; Chow, T.; Garakian, J.; Vinters, H.V.; Cummings, J.L. Orbitofrontal and anterior cingulate cortex neurofibrillary tangle burden is associated with agitation in Alzheimer disease. Ann. Neurol., 2001, 49(3), 355-361.
[http://dx.doi.org/10.1002/ana.72] [PMID: 11261510]
[19]
Victoroff, J.; Zarow, C.; Mack, W. Physical aggression is associated with preservation of substantia nigra pars compacta in Alzheimer's disease. Arch. Neurol., 1996, 53(2), 428-434.
[20]
Sweet, R.; Pollock, B. The 5-HTTPR polymorphism confers liability to a combined phenotype of psychotic and aggressive behavior in Alzheimer's disease. Int. Psychogeriatr., 2001, 13(4), 401-409.
[21]
Kales, H.; Lyketsos, C. Management of behavioral and psychological symptoms in people with Alzheimer's disease: An international Delphi consensus. Int. Psychogeriatr., 2018, 31(1), 83-90.
[22]
Ballard, C.; Gauthier, S. Management of agitation and aggression associated with Alzheimer's disease. Nat. Rev. Neurol., 2009, 5, 245-255.
[23]
Tampi, R. Antipsychotic use in dementia: A systematic review of benefits and risks from meta-analyses. Ther. Adv. Chronic Dis., 2016, 7(5), 229-245.
[24]
Mittal, V.; Kurup, L.; Williamson, D.; Muralee, S.; Tampi, R.R. Risk of cerebrovascular adverse events and death in elderly patients with dementia when treated with antipsychotic medications: A literature review of evidence. Am. J. Alzheimer's Dis. Other Dement., 2011, 26(1), 10-28.
[http://dx.doi.org/10.1177/1533317510390351]
[25]
Home - Acadia Pharmaceuticals. Available from:https://acadia.com/ (Accessed on: 20 December 2022).
[26]
Srinivasan, S.; Tampi, R. Pimavanserin for the treatment of psychosis in Alzheimer's disease: A literature review. World J. Psychiatry, 2020, 10(7), 162-174.
[27]
Ballard, C.; Youakim, J.M.; Coate, B.; Stankovic, S. Pimavanserin in alzheimer’s disease psychosis: Efficacy in patients with more pronounced psychotic symptoms. J. Prev. Alzheimers Dis., 2019, 6(1), 27-33.
[PMID: 30569083]
[28]
Tariot, PN; Cummings, JL; Soto-Martin, ME; Ballard, C; Erten-Lyons, D; Sultzer, DL Trial of pimavanserin in dementia-related psychosis. N. Engl. J. Med., 2021, 385(4), 309-19.
[29]
Horn, S.; Richardson, H.; Xie, S. Pimavanserin versus quetiapine for the treatment of psychosis in Parkinson's disease and dementia with Lewy bodies. Parkinsonism Relat. Disord., 2019, 69, 119-124.
[30]
Nasrallah, H.; Fedora, R. Successful treatment of clozapine-nonresponsive refractory hallucinations and delusions with pimavanserin, a serotonin 5HT-2A receptor inverse agonist. Schizophr Res., 2019, 208, 217-220.
[31]
Crump, C.J.; Litteral, C.A.; Elsayed, O.H.; El-Mallakh, R.S. Pimavanserin for bipolar disorder. Bipolar Disord., 2022, 24(6), 697-699.
[http://dx.doi.org/10.1111/bdi.13191] [PMID: 35167172]
[32]
Bugarski-Kirola, D.; Arango, C.; Fava, M.; Nasrallah, H.; Liu, I.Y.; Abbs, B.; Stankovic, S. Pimavanserin for negative symptoms of schizophrenia: Results from the ADVANCE phase 2 randomised, placebo-controlled trial in North America and Europe. Lancet Psychiatry, 2022, 9(1), 46-58.
[http://dx.doi.org/10.1016/S2215-0366(21)00386-2] [PMID: 34861170]
[33]
Yasue, I.; Matsunaga, S. Serotonin 2A receptor inverse agonist as a treatment for parkinson's disease psychosis: A systematic review and meta-analysis of serotonin 2a receptor negative modulators. J. Alzheimers Dis., 2016, 50(3), 733-40.
[34]
Fava, M.; Dirks, B.; Freeman, M.P.; Papakostas, G.I.; Shelton, R.C.; Thase, M.E.; Trivedi, M.H.; Liu, K.; Stankovic, S. A phase 2, randomized, double-blind, placebo-controlled ST of adjunctive pimavanserin in patients with major depressive disorder and an inadequate response to therapy (CLARITY). J. Clin. Psychiatry, 2019, 80(6)
[http://dx.doi.org/10.4088/JCP.19m12928]
[35]
Ancoli-Israel, S.; Vanover, K.E.; Weiner, D.M.; Davis, R.E.; van Kammen, D.P. Pimavanserin tartrate, a 5-HT2A receptor inverse agonist, increases slow wave sleep as measured by polysomnography in healthy adult volunteers. Sleep Med., 2011, 12(2), 134-141.
[http://dx.doi.org/10.1016/j.sleep.2010.10.004] [PMID: 21256805]

Rights & Permissions Print Cite
Article Metrics
47
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy