title: Progresses in treating agitation: a major clinical challenge in Alzheimer's disease.
abstract: BACKGROUND
  Treatment of neuropsychiatric symptoms (NPS) represents a major clinical challenge in Alzheimer's disease (AD). Agitation and aggression are frequently seen during institutionalization and increase patient morbidity and mortality and caregiver burden. Off-label use of atypical antipsychotics for treating agitation in AD showed only modest clinical benefits, with high side-effect burden and risk of mortality. Non-pharmacological treatment approaches have become the preferred first-line option. When such treatment fails, pharmacological options are often used. Therefore, there is an urgent need to identify effective and safe pharmacological treatments for efficiently treating agitation and aggression in AD and dementia.
  
  
  METHODS
  Emerging evidence on the neurobiological substrates of agitation in AD has led to several recent clinical trials of repositioned and novel therapeutics for these NPS in dementia as an alternative to antipsychotics. We operated a comprehensive literature search for published articles evaluating pharmacological interventions for agitation in AD, with a review of recent clinical trials on mibampator, dextromethorphan/quinidine, cannabinoids, and citalopram.
  
  
  CONCLUSIONS
  Notwithstanding the renewed interest for the pharmacological treatment of agitation in AD, progresses have been limited. A small number and, sometimes methodologically questionable, randomized controlled trials (RCTs) have produced disappointing results. However, recently completed RCTs on novel or repositioned drugs (mibampator, dextromethorphan/quinidine, cannabinoids, and citalopram) showed some promise in treating agitation in AD, but still with safety concerns. Further evidence will come from ongoing Phase II and III trials on promising novel drugs for treating these distressing symptoms in patients with AD and dementia.
authors.affiliation: a 1 University of Bari Aldo Moro, Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs , Bari, Italy , geriat.dot@geriatria.uniba.it.|b 2 University of Bari Aldo Moro, Department of Clinical Research in Neurology, "Pia Fondazione Cardinale G. Panico" , Tricase, Lecce, Italy.|c 3 Geriatric Unit & Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza" , San Giovanni Rotondo, Foggia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Panza
authors.affiliation: d 4 University of Bari Aldo Moro, Geriatric Medicine-Memory Unit and Rare Disease Centre , Bari, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Solfrizzi
authors.affiliation: c 3 Geriatric Unit & Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza" , San Giovanni Rotondo, Foggia, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.affiliation: e 5 Research & Development Department, Chiesi Farmaceutici , Parma, Italy.
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Imbimbo
authors.affiliation: f 6 University of Foggia, Physical Medicine and Rehabilitation Section, "OORR" Hospital , Foggia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Santamato
authors.affiliation: a 1 University of Bari Aldo Moro, Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs , Bari, Italy , geriat.dot@geriatria.uniba.it.
authors.forename: Madia
authors.initials: M
authors.lastname: Lozupone
authors.affiliation: g 7 Geriatrics Unit, Department of OrthoGeriatrics, Rehabilitation and Stabilization, Frailty Area, Galliera Hospital NR-HS , Genova, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Prete
authors.affiliation: c 3 Geriatric Unit & Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza" , San Giovanni Rotondo, Foggia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Greco
authors.affiliation: g 7 Geriatrics Unit, Department of OrthoGeriatrics, Rehabilitation and Stabilization, Frailty Area, Galliera Hospital NR-HS , Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pilotto
authors.affiliation: a 1 University of Bari Aldo Moro, Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs , Bari, Italy , geriat.dot@geriatria.uniba.it.|b 2 University of Bari Aldo Moro, Department of Clinical Research in Neurology, "Pia Fondazione Cardinale G. Panico" , Tricase, Lecce, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Logroscino
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D058492:Drug Repositioning; D006801:Humans; D056687:Off-Label Use; D011595:Psychomotor Agitation / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents
keywords: Alzheimer’s disease; aggression; agitation; antidepressants; antipsychotics; brexpiprazole; cannabinoids; citalopram; dementia; dextromethorphan/quinidine; dronabinol; mibampator; neuropsychiatric symptoms; prazosin; risperidone; scyllo-inositol; selective serotonin reuptake inhibitors: treatment