An update on the advancements in the treatment of agitation in Alzheimer’s disease

References

• Alzheimer’s Disease International: World Alzheimer Report. London: Alzheimer’s Disease International (ADI); 2015.
   Google Scholar
• McKeith I, Cummings J. Behavioural changes and psychological symptoms in dementia disorders. Lancet Neurol. 2005;4(11):735–742.
   PubMed Web of Science ®Google Scholar
• Steinberg M, Shao H, Zandi P, et al. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the cache county study. Int J Geriatr Psychiatry. 2008;23(2):170–177.
   PubMed Web of Science ®Google Scholar
• Gonfrier S, Andrieu S, Renaud D, et al. Course of neuropsychiatric symptoms during a 4-year follow up in the REAL-FR cohort. J Nutr Health Aging. 2012;16(2):134–137.
   PubMed Web of Science ®Google Scholar
• Kales HC, Gitlin LN, Lyketsos CG. Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panel. J Am Geriatr Soc. 2014;62(4):762–769.
   PubMed Web of Science ®Google Scholar
• Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. Jama. 2014;311(7):682–691.
   PubMed Web of Science ®Google Scholar
• Cummings J, Mintzer J, Brodaty H, et al. Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition. Int Psychogeriatrics. 2015 1;27(01):7–17.
   PubMed Web of Science ®Google Scholar
• Gitlin LN, Kales HC, Lyketsos CG. Nonpharmacologic management of behavioral symptoms in dementia. Jama. 2012;308(19):2020–2029.
   PubMed Web of Science ®Google Scholar
• Antonsdottir IM, Smith J, Keltz M, et al. Advancements in the treatment of agitation in Alzheimer’s disease. Expert Opin Pharmacother. 2015;16(11):1649–1656.
   PubMed Web of Science ®Google Scholar
• Maher AR, Maglione M, Bagley S, et al. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis. Jama. 2011;306(12):1359–1369.
   PubMed Web of Science ®Google Scholar
• Drye LT, Ismail Z, Porsteinsson AP, et al. Citalopram for agitation in Alzheimer’s disease: design and methods. Alzheimers Dement. 2012;8(2):121–130.
   PubMed Web of Science ®Google Scholar
• Ballard C, Howard R. Neuroleptic drugs in dementia: benefits and harm. Nat Rev Neurosci. 2006;7(6):492–500.
   PubMed Web of Science ®Google Scholar
• Langballe EM, Engdahl B, Nordeng H, et al. Short-and long-term mortality risk associated with the use of antipsychotics among 26,940 dementia outpatients: a population-based study. Am J Geriatr Psychiatry. 2014;22(4):321–331.
   PubMed Web of Science ®Google Scholar
• Schneider LS, Pollock VE, Lyness SA. A metaanalysis of controlled trials of neuroleptic treatment in dementia. J Am Geriatr Soc. 1990;38:553–563.
   PubMed Web of Science ®Google Scholar
• Lonergan E, Luxenberg J, Colford J. Haloperidol for agitation in dementia. Cochrane Database Syst Rev. 2002;(2):CD002852.
   Google Scholar
• Geda YE, Schneider LS, Gitlin LN, et al. Neuropsychiatric symptoms in Alzheimer’s disease: past progress and anticipation of the future. Alzheimers Dement. 2013;9(5):602–608.
   PubMed Web of Science ®Google Scholar
• van Dam D, Vermeiren Y, Dekker AD, et al. Neuropsychiatric disturbances in Alzheimer’s disease: what have we learned from neuropathological studies? Curr Alzheimer Res. 2016;13(10):1145–1164.
   PubMed Web of Science ®Google Scholar
• Cummings JL, Lyketsos CG, Peskind ER, et al. Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA. 2015;314(12):1242–1254.
   PubMed Web of Science ®Google Scholar
• Townsend M, Cleary JP, Mehta T, et al. Orally available compound prevents deficits in memory caused by the Alzheimer amyloid‐β oligomers. Ann Neurol. 2006;60(6):668–676.
   PubMed Web of Science ®Google Scholar
• Tariot P, Lyketsos C, Crans G, et al. The effects of ELND005 (scyllo-inositol) on emergence of neuropsychiatric symptoms (NPS) in mild/moderate Alzheimer’s disease: results from a 78-week phase 2 study (P04. 215). Neurology. 2012;78(MeetingAbstracts 1):PP04.215-215.
   Google Scholar
• Salloway S, Sperling R, Keren R, et al. A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology. 2011;77(13):1253–1262.
   PubMed Web of Science ®Google Scholar
• Porsteinsson AP, Abushakra S, Boada M, et al. ELND005 for agitation and aggression in Alzheimer’s disease (HARMONY-AD study): phase 2/3 design and clinical outcomes. J Prev Alzheimer’s Dis JPAD. 2015;2(4):OC20.
   Google Scholar
• Maeda K, Sugino H, Akazawa H, et al. Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther. 2014 Sep;350(3):589–604.
   PubMed Web of Science ®Google Scholar
• Haase N, Herse F, Spallek B, et al. Vasoactivity of the Alzheimer ss-amyloid peptides is mediated by an activation of the a1-adrenoreceptor. Hypertension. 2013;62(3_MeetingAbstracts):A459.
   Google Scholar
• Katsouri L, Vizcaychipi MP, McArthur S, et al. Prazosin, an α 1-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer’s disease. Neurobiol Aging. 2013;34(4):1105–1115.
   PubMed Web of Science ®Google Scholar
• Peskind ER, Bonner LT, Li G, et al. Adrenergic antagonists for disruptive agitation in nursing home residents with Alzheimer’s disease. Neurobiol aging: the 8th international conference on Alzheimer’s disease and related disorders. 2002;23:S150.
   Google Scholar
• Wang LY, Shofer JB, Rohde K, et al. Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression. Am J Geriatr Psychiatry. 2009;17(9):744–751.
   PubMed Web of Science ®Google Scholar
• Peskind ER, Raskind MA, Wang L. Two pilot studies of the alpha-1 adrenoreceptor antagonist prazosin for agitation/aggression in AD lead to an Alzheimer’s disease cooperative study multicenter trial. Alzheimers Dement. 2014;10(4):P821.
   Google Scholar
• Antonsdottir IM, Porsteinsson AP. Dazed and confused: medical cannabis in Alzheimer disease. Am J Geriatr Psychiatry. 2016;24(11):1004–1006.
   PubMed Web of Science ®Google Scholar
• Ramirez BG, Blazquez C, Gomez Del Pulgar T, et al. Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci. 2005 Feb 23;25(8):1904–1913.
   PubMed Web of Science ®Google Scholar
• Woodward MR, Harper DG, Stolyar A, et al. Dronabinol for the treatment of agitation and aggressive behavior in acutely hospitalized severely demented patients with noncognitive behavioral symptoms. Am J Geriatr Psychiatry. 2014;22(4):415–419.
   PubMed Web of Science ®Google Scholar
• Shelef A, Barak Y, Berger U, et al. Safety and efficacy of medical cannabis oil for behavioral and psychological symptoms of dementia: an-open label, add-on, pilot study. J Alzheimers Dis. 2016;51(1):15–19.
   PubMed Web of Science ®Google Scholar
• van den Elsen GAH, Ahmed AIA, Verkes R-J, et al. Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: a randomized controlled trial. Neurology. 2015;84(23):2338–2346.
   PubMed Web of Science ®Google Scholar
• Drye LT, Spragg D, Devanand DP, et al. Changes in QTc interval in the citalopram for agitation in Alzheimer’s disease (CitAD) randomized trial. Plos One. 2014 Jun 10;9(6):e98426.
   PubMedGoogle Scholar
• Leonpacher A, Peters ME, Drye LT, et al. Effects of citalopram on neuropsychiatric symptoms in Alzheimer’s dementia: evidence from the CitAD study. Am J Psychiatry. 2016 May 1;173(5):473–480.
   PubMed Web of Science ®Google Scholar
• Schneider LS, Frangakis C, Drye LT, et al. Heterogeneity of treatment response to citalopram for Alzheimer disease patients with aggression or agitation: the CitAD randomized clinical trial. Am J Psychiatry. 2016 May 1;173(5):465–472.
   PubMed Web of Science ®Google Scholar
• Ho T, Pollock BG, Mulsant BH, et al. R-and S-citalopram concentrations have differential effects on neuropsychiatric scores in elders with dementia and agitation. Br J Clin Pharmacol. 2016 Sep;82(3):784–792.
   PubMed Web of Science ®Google Scholar
• Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. The Lancet. 2014;383(9916):533–540.
   PubMed Web of Science ®Google Scholar
• Snyder GL, Vanover KE, Zhu H, et al. Functional profile of a novel modulator of serotonin, dopamine, and glutamate neurotransmission. Psychopharmacology. 2015;232:605–621.
   PubMed Web of Science ®Google Scholar
• Rinne JO, Wesnes K, Cummings JL, et al. Tolerability of ORM-12741 and effects on episodic memory in patients with Alzheimer disease. Alzheimers Dement. 2017 Jan;3(1):1–9.
   Google Scholar