Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement) (66). ChildrenUse and dose must be determined by your doctor. Pain, agitation, and behavioural problems in people with dementia admitted to general hospital wards: a longitudinal cohort study, Management of agitation in huntington's disease: a review of the literature. In Figure 2, we propose an approach to treat patients with agitation properly. For instance, in a 12-week prospective study, AD patients with agitated behavior receiving 1530 mg/day of mirtazapine showed a significant reduction in CMAI-short form (CMAI-SF) after treatment (112). Pharmacologic Management of Agitation in Patients with Dementia Careers. HHS Vulnerability Disclosure, Help Moved Permanently. Rapp MA, Schnaider-Beeri M, Purohit DP, Perl DP, Haroutunian V, Sano M. Increased neurofibrillary tangles in patients with Alzheimer disease with comorbid depression. McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor J-P, Weintraub D, et al.. 2005 Apr 18;2005(2):CD003729. Mild behavioral impairment and risk of dementia: a prospective cohort study of 358 patients. Agitation is a common behavioral disturbance featuring exaggerated motor activity and verbal and/or physical aggressiveness, severe enough to impair social relations and daily living activities (1). Nonetheless, not every PCC-based strategy is effective. In FTD, even though the data are still controversial, agitation appears to be related to increased dopaminergic transmission (31). CLINICAL. Background Information Behavioural and Psychological Symptoms of Dementia (BPSD) Substance withdrawal should also be considered as a possible trigger for agitation (48). Homdee N, Alam R, Hayes JA, Hamid T, Park J, Wolfe S, et al.. Agitation monitoring and prevention system for dementia caregiver empowerment. According to several observations, agitation prevalence ranges from 30 to 50% in Alzheimer's disease, 30% in dementia with Lewy bodies, 40% in frontotemporal dementia, and 40% in vascular dementia (VaD). hyper- or hypoglycemia, electrolyte disturbance, renal or hepatic Compared with aripiprazole and brexpiprazole, the molecule shows less activity at the D2 receptor, thereby generating a more tolerable side effects profile. 2020 Jan 21;1(1):CD004770. It increases levels of the brain chemical gamma-aminobutyric acid. Antipsychotics for elderly people with dementia: Which are best? Compared with placebo, only citalopram was found to be more efficacious in the short-term hospital treatment of psychotic symptoms, Efficacy of risperidone and citalopram for psychotic symptoms and agitation, respectively Second endpoint: citalopram would be associated with fewer side effects, Agitation and psychotic symptoms decreased in both treatment groups without significant differences. Moreover, agitation is associated with a higher admission rate to assisted living facilities, higher use of medications, long-term hospitalization, and higher mortality (5). Non-pharmacological toxic agents also need to be considered, especially in suspected carbon monoxide or alcohol intoxications. However, the presence of pain (93) and intercurrent pathologic conditions (94) (e.g., infections, dehydration, metabolic imbalance) has been associated with the onset of aggressiveness, anxiety, and agitation and should be addressed. National Library of Medicine Lorazepam oral tablet side effects: How to manage them Edited by: David Gordon Lichter, University at Buffalo, United States, Reviewed by: Antonina Luca, University of Catania, Italy; Judith Aharon Peretz, Rambam Health Care Campus, Israel, This article was submitted to Dementia and Neurodegenerative Diseases, a section of the journal Frontiers in Neurology. Catic AG, Mattison MLP, Bakaev I, Morgan M, Monti SM, Lipsitz L. ECHO-AGE: an innovative model of geriatric care for long-term care residents with dementia and behavioral issues, Immersive virtual reality and persons with dementia: a literature review. The overt agitation severity scale for the objective rating of agitation. NICE Advice; Evidence summaries; Management of aggression, agitation and behavioural disturbances in dementia: valproate preparations. Finally, the occurrence of hyperkinetic delirium and agitation has been reported also during the recovery phase from COVID 19, in the absence of direct brain infection (208). Sampson EL, White N, Lord K, Leurent B, Vickerstaff V, Scott S, et al.. Advice. Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR. Members of the network select questions based on their relevance to family medicine. Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors, Pharmacological recommendations for the symptomatic treatment of dementia: the Canadian consensus conference on the diagnosis and treatment of dementia 2012, Behavioural abnormalities associated with rapid deterioration of language functions in semantic dementia respond to sertraline, Frontotemporal dementia: recommendations for therapeutic studies, designs, and approaches, Frontotemporal dementia treatment: current symptomatic therapies and implications of recent genetic, biochemical, and neuroimaging studies. Before Few data, including mainly case reports and small case series, are available for other anticonvulsants (gabapentin, levetiracetam, topiramate, and lamotrigine) (115). Cognitive effects differed somewhat between Alzheimer patients and normal . This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). A sequential drug treatment algorithm for agitation and aggressiveness associated with AD and mixed dementia, such as AD/VaD, has been lately proposed (168). However, the risk of well-known side effects limits their use to only severe conditions (33). For instance, the Dementia Care Mapping (DCM) (69, 72, 73), which is based on patients' systematic observations, has generated conflicting results. Ballard C, Margallo-Lana M, Juszczak E, Douglas S, Swann A, Thomas A, et al.. Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial. Current Treatments of Agitation and Aggression Ativan Tablets Dosage Guide Dosage and duration of antipsychotic treatment in demented outpatients with agitation or psychosis. FOIA Isidoro Hospital, Trescore Balneario, Italy. D'Cunha NM, Nguyen D, Naumovski N, McKune AJ, Kellett J, Georgousopoulou EN, et al.. A mini-review of virtual reality-based interventions to promote well-being for people living with dementia and mild cognitive impairment, Use and impact of virtual reality simulation in dementia care education: a scoping review. These drugs can aid in managing anxiety symptoms like the following: Worry. A valid option is offered by the Geriatric Monitoring Unit (GMU) (101, 102). Lorazepam is used to treat anxiety disorders. Less commonly reported adverse effects include: Blood and lymphatic system disorders such as thrombocytopenia, leucopenia, agranulocytosis, and pancytopenia. Among NPS, antipsychotic resulted to be more effective for specific behavioral symptoms, such as agitation (155). Dementia. Surr CA, Holloway I, Walwyn REA, Griffiths AW, Meads D, Martin A, et al.. Rokstad AMM, Rsvik J, Kirkevold , Selbaek G, Saltyte Benth J, Engedal K. The effect of person-centred dementia care to prevent agitation and other neuropsychiatric symptoms and enhance quality of life in nursing home patients: a 10-month randomized controlled trial. Prazosin, an alpha-adrenoreceptor blocking drug, demonstrated a significant impact on agitation and aggressiveness in a daily dose ranging from 1 to 6 mg (164), but it is not recommended in patients who have experienced orthostatic hypotension (165). Considerations and current trends in the management of the geriatric patient on a consultation-liaison service. The present review provides a toolbox for the detection, prevention, and therapeutical management of acute and chronic agitation in patients suffering from neurodegenerative conditions. Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer's disease and dementia with lewy bodies. D'Ardes D, Carrarini C, Russo M, Dono F, Speranza R, Digiovanni A, et al.. Low molecular weight heparin in COVID-19 patients prevents delirium and shortens hospitalization. Several studies have considered agitation as indicative of the external expression of anxiety (68). Liptzin B, Laki A, Garb JL, Fingeroth R, Krushell R. Donepezil in the prevention and treatment of post-surgical delirium, Summary of the comparative effectiveness review on off-label use of atypical antipsychotics. Which Emergent Medication Should I Give Next? Neurotransmitter alterations (e.g., a reduction in dopamine and acetylcholine transmission) can also promote acute agitation in elderly patients (48). While THC failed to show efficacy in reducing agitation or aggressiveness, dronabinol showed effects on nighttime agitation (223). Drug therapy for delirium in terminally ill adults. Except they aren't - they've lost their non-slip grip. Pro re nata (PRN) injections of psychotropics can be administered for severe acute agitation, but little is known about the frequency of their actual use. . Nordstrom K, Zun LS, Wilson MP, Stiebel V, Ng AT, Bregman B, et al.. Medical evaluation and triage of the agitated patient: consensus statement of the American association for emergency psychiatry project BETA medical evaluation workgroup, Comparison of self-reported to observational agitation scales. Rather than a stand-alone entity, VaD should be regarded as part of a Mixed dementia phenotype, particularly in elderly subjects (167). Furthermore, passive listening to music has been associated with behavioral improvement and reduction of aggressiveness and agitation (76). Vital signs monitoring is mandatory to manage life-threatening conditions, such as cardiocirculatory or respiratory failure. Between 80 and 90 percent of persons with dementia experience psychosis, agitation, or . Finally, the metabotropic glutamate receptor 2 (mGluR2), N-methyl-d-aspartate receptor (NMDA), muscarinic acetylcholine receptor M4 (M4R), and M1/M4 receptors (M1/M4R) (217) are also promising targets of future intervention. This study was funded by the Alzheimer's Association Part the Cloud: Translational Research Funding for Alzheimer's Disease (PTC) PTC-19-602325 and the Alzheimer's AssociationGAAIN Exploration to Evaluate Novel Alzheimer's Queries (GEENA-Q-19-596282) (SLS). Agitation is a common behavioral disturbance featuring exaggerated motor activity and verbal and/or physical aggressiveness, severe enough to impair social relations and daily living activities ( 1 ). Moreover, selective serotonin reuptake inhibitors (SSRIs), such as citalopram, escitalopram, and sertraline, have demonstrated efficacy in AD patients (111, 156). Lexapro has an average rating of 7.5 out of 10 from a total of 2269 ratings on Drugs.com. Cohen-Mansfield J, Dakheel-Ali M, Marx MS, Thein K, Regier NG. Mirtazapine, an antidepressant with alpha-2 adrenergic, 5-HT2, and 3-HT2 antagonist properties, showed promising results in open-label studies. Logroscino G, Imbimbo BP, Lozupone M, Sardone R, Capozzo R, Battista P, et al.. Keywords: agitation, antipsychotic, haloperidol, olanzapine, diazepam, lorazepam, aripiprazole, ziprasidone, risperidone, benzodiazepine Introduction and background Rapid tranquilization is a term denoting the use of pharmacological agents to calm acutely agitated or aggressive patients, both in a psychiatric as well as a general acute care . Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal P V, Keane KA, et al.. Dextromethorphan was deuterated to improve its pharmacokinetic profile and reduce its first-pass metabolism in the liver (221). Agitation adversely impacts cognitive performance, functional status, and patients' quality of life and enhances caregiver's distress. Tampi RR, Tampi DJ, Young J, Hoq R, Resnick K. The place for electroconvulsive therapy in the management of behavioral and psychological symptoms of dementia. The clinical effects of sertraline, fluoxetine, and citalopram are controversial. Four trials assessed the rates of withdrawal because of adverse effects from SSRIs vs. placebo. This effect is considered to be driven by a positive exploration of repressed feelings (76). Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. Leroi I, Brandt J, Reich SG, Lyketsos CG, Grill S, Thompson R, et al.. Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson's disease. Pilotto A, Masciocchi S, Volonghi I, Crabbio M, Magni E, De Giuli V, et al.. Clinical presentation and outcomes of SARS-CoV-2 related encephalitis: the ENCOVID multicentre study. Lorazepam is an antidepressant generally used to treat anxiety. Devlin JW, Boleski G, Mlynarek M, Nerenz DR, Peterson E, Jankowski M, et al.. Motor activity assessment scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit. A recent review proposed risperidone as a first-choice agent for agitation and aggression among dementia patients . Efficacy in controlling agitation was established in 4 double-blind controlled pivotal trials . Ellul MA, Benjamin L, Singh B, Lant S, Michael BD, Easton A, et al.. COVID-19 impact on consecutive neurological patients admitted to the emergency department. Small, placebo-controlled studies on carbamazepine found evidence of modest benefits for agitation and aggression in AD patients (115). Pedersen SKA, Andersen PN, Lugo RG, Andreassen M, Stterlin S. Effects of music on agitation in dementia: a meta-analysis. The Behavioral Activity Rating Scale (BARS) is often used in clinical trials. All the agitated patients admitted to the hospital should be assessed with the help of laboratory testing (including the assessment of blood cell counts, glucose levels, electrolytes, creatinine, blood urea nitrogen, transaminases, C-reactive protein, procalcitonin, and urine tests) to rule out certain conditions, such as anemia, intercurrent infections, and liver or kidney failure. Funding. Huang HC, Wang YT, Chen KC, Yeh TL, Lee IH, Chen PS, et al.. Howard RJ, Juszczak E, Ballard CG, Bentham P, Brown RG, Bullock R, et al.. Donepezil for the treatment of agitation in Alzheimer's disease. The phase IV clinical study analyzes which people take Ativan and have Agitation. Olanzapine (Zyprexa) and risperidone reduce dementia-related agitation much longer than placebo. If benzodiazepines are deemed the most appropriate therapy, short-acting agents such as lorazepam and midazolam should be used instead of long-acting agents such as diazepam. Neuropsychiatric symptoms in Alzheimer disease, vascular dementia, and mixed dementia. Treatment Options for Acute Agitation in Psychiatric Patients Hence, the treatment with neuroleptics should be avoided in agitated patients with DLB/PDD. doi: 10.1002/14651858.CD004770.pub3. Comparison and agreement between the richmond agitation-sedation scale and the riker sedation-agitation scale in evaluating patients' eligibility for delirium assessment in the ICU. In particular, clozapine (average dose 44.6 mg/day) (185) and quetiapine (5075 mg/day) (117), atypical neuroleptics with weak affinity for dopamine D2 receptors, have achieved benefits in the management of agitation in patients with dementia and parkinsonism (117, 185). Delli Pizzi S, Padulo C, Brancucci A, Bubbico G, Edden RA, Ferretti A, et al.. GABA content within the ventromedial prefrontal cortex is related to trait anxiety. The American psychiatric association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Adult 1-2 mg daily, to be taken at bedtime. Donepezil improves symptoms of delirium in dementia: implications for future research. Treatment for Alzheimer's Living & Caregiving Managing Day-to-Day. Several experts have agreed that, to optimize the clinical response, patients with dementia should be treated with specific and novel medications interacting with pharmacologically relevant targets (209211). Dextromethorphan/quinidine was also more effective than placebo (OR = 3.04; 95% CI, 1.63 to 5.66; NNT = 5), but it was evaluated in only one RCT. PDF Acute Agitation Treatment Reference Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: a randomised, controlled trial with trazodone. Additionally, the Citalopram for Agitation in Alzheimer Disease Study (CitAD), a placebo-controlled double-blind RCT, showed a high acceptability rate and efficacy for citalopram over placebo in the treatment of agitation (108). Among antipsychotic agents, risperidone, quetiapine, olanzapine, aripiprazole, and clozapine showed efficacy on the agitation of FTD patients, but, because of their low safety profile, the drugs are recommended only as a second-line treatment (194196). Short-term use in anxiety for lorazepam By mouth. In this extension study, three different dextromethorphan doses are administered twice a day over 52 weeks. . Lorazepam, a member of the benzodiazepine class, has long been used for the short-term treatment of anxiety, first receiving US Food and Drug Administration (FDA) approval in 1977 as an immediate-release (IR) formulation (Ativan). Panza F, Solfrizzi V, Seripa D, Imbimbo BP, Santamato A, Lozupone M, et al.. . Meehan KM, Wang H, David SR, Nisivoccia JR, Jones B, Beasley CM Jr, Feldman PD, Mintzer JE, Beckett LM, Breier A. Neuropsychopharmacology. Lorazepam (Oral Route) Proper Use The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. De Mendona A, Ribeiro F, Guerreiro M, Garcia C. Aggression, agitation, hyperactivity, and irritability, Neuropsychiatric Symptoms of Cognitive Impairment and Dementia, Agitation in dementia: concept clarification, Sundowning and other temporally associated agitation states in dementia patients. Dementia affects 5 percent of adults older than 65 years and up to 30 percent of persons older than 85 years. Emre M, Aarsland D, Albanese A, Byrne EJ, Deuschl G, De Deyn PP, et al.. Rivastigmine for dementia associated with Parkinson's disease. PDF Acute Agitation You can use the study as a second opinion to make health care decisions. In acute agitation, a non-contrast head computed tomography (CT) should be obtained when an intracranial origin is suspected (48), especially in the presence of focal neurological signs. As expected, the safety of lorazepam among the different studies was consistent with its well-characterized profile with dizziness, sedation, and somnolence being the most common adverse events. Unauthorized use of these marks is strictly prohibited. However, it is safe to say that pharmacological treatments should be implemented as a second choice, whereas non-pharmacological interventions should be person-centered, preferred, and prioritized. A mGluR2 agonist, LY2979165, is not investigated in one phase II clinical trial. For instance, in a multicenter, double-blind, placebo-controlled trial, 421 outpatients suffering from AD with psychosis, aggressiveness, or agitation were randomly assigned to receive olanzapine (mean dose 5.5 mg/day), quetiapine (mean dose 56.5 mg/day), risperidone (mean dose 1.0 mg/day), or placebo. Therefore, one can envision drugs targeting mGluR, NMDA receptors, cannabinoid receptor type 1 (CB1R), M1/M4R, and 5-HT6R to be soon part of the pharmacological armamentarium employed for dementia-related agitation. Findings from a pilot randomised controlled trial, Implementation of a baby doll therapy protocol for people with dementia: innovative practice. Building on the prior definitions of a pre-dementia risk state (35, 36) and frontotemporal-MCI (37), the ISTAART NPS-PIA formally described MBI as the emergence of sustained and impactful NPS occurring after the age of 50, which are not encompassed in the psychiatric nosology, persist for at least 6 months, and manifest before or at the onset of MCI (34). *indicates not sufficiently supported by clinical evidence; AD, Alzheimer's disease; DLB, dementia with Lewy bodies; PDD, Parkinson's disease with dementia; VaD, vascular dementia; FTD, frontotemporal dementia; AChEIs, acetylcholinesterase inhibitors; BZDs, benzodiazepines; SSRIs, selective serotonin reuptake inhibitors. (SOR = B, based on one medium-quality RCT.) One trial comparing citalopram and risperidone measured change on the Neurobehavioral Rating Scale (a 28-item observer-rated scale using seven gradations ranging from not present [1 point] to extremely severe [7 points]) and showed similar effectiveness (mean difference = 0.53 points; 95% CI, 2.37 to 1.31) and no significant difference in withdrawal because of adverse effects. Available evidence indicates that benzodiazepines are commonly used to treat various disorders including anxiety, insomnia, agitation, alcohol withdrawal, and seizures. Fox C, Crugel M, Maidment I, Auestad BH, Coulton S, Treloar A, et al.. Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial. Received 2020 Dec 20; Accepted 2021 Mar 12. Dose is based on the total daily dose of lorazepam tablets, which you take three times a day in equally divided doses. Three previous RCTs showed comparable clinical efficacy of atypical antipsychotics and haloperidol (137, 139, 140). Pharmacology of dextromethorphan: relevance to dextromethorphan/quinidine (Nuedexta) clinical use, AVP-786 for the treatment of agitation in dementia of the Alzheimer's type. Copyright 2021 by the American Academy of Family Physicians. Chong MS, Chan MPC, Kang J, Han HC, Ding YY, Tan TL. Use of Benzodiazepines in Alzheimer's Disease: A Systematic Review of Hence, given the increasing presence of this condition and its related burden on society and the health system, the present point of view aims at providing an extensive guide to facilitate the identification, prevention, and management of acute and chronic agitation in dementia patients. The pathophysiological mechanism underlying agitation is represented by a frontal lobe dysfunction, mostly involving the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC), respectively, meaningful in selecting the salient stimuli and subsequent decision-making and behavioral reactions. Ravina B, Putt M, Siderowf A, Farrar JT, Gillespie M, Crawley A, et al.. Donepezil for dementia in Parkinson's disease: a randomised, double blind, placebo controlled, crossover study. At 24 weeks, there were no significant improvements in agitation between citalopram and quetiapine as measured by two agitation scales (i.e., the Neuropsychiatric Inventory [NPI] scale: regression coefficient = 0.022; 95% CI, 0.093 to 0.137; P = .882 and the modified Alzheimer's Disease Cooperative StudyClinical Global Impression of Change [mADCS-CGIC] scale: OR = 1.00; 95% CI, 0.92 to 1.07; P = .935), or between citalopram and olanzapine (NPI scale: regression coefficient = 0.041; 95% CI, 0.068 to 0.036; P = .409 and mADCS-CGIC scale: OR = 0.98; 95% CI, 0.86 to 1.20; P = .849). What Is Dementia? Teri L, Logsdon RG, Peskind E, Raskind M, Weiner MF, Tractenberg RE, et al.. Hospitalization is another well-known trigger of agitation either alone or as a manifestation of hyperkinetic delirium in people with dementia (41). It is also used for short-term relief of the symptoms of anxiety or anxiety caused by depression. Copyright Family Physicians Inquiries Network. Treating Agitation in Alzheimer's Disease A teleconsultation system based on expert's recommendations, namely, ECHO-AGE, has also provided clinical improvement in nursing home settings when dealing with agitated patients (86). Room transfers and the risk of delirium incidence amongst hospitalized elderly medical patients: a case-control study, Matching the environment to patients with delirium: lessons learned from the delirium room, a restraint-free environment for older hospitalized adults with delirium. Van Velthuijsen EL, Zwakhalen SMG, Mulder WJ, Verhey FRJ, Kempen GIJM. The first step in treating agitation of parkinsonian patients should be an accurate revision of current treatment. In elderly patients, acute agitation can be the expression of a wide range of conditions, including medical, psychiatric, and substance-induced alterations (46) (Table 1). Moreover, the presence of substance-induced agitation should always be considered. Johnson JK, Head E, Kim R, Starr A, Cotman CW. A modest benefit on cognitive function was observed, Trazodone is an effective treatment for the behavioral symptoms of FTD, Efficacy, safety, and tolerability of rivastigmine capsules, Rivastigmine did not provide consistent efficacy. sharing sensitive information, make sure youre on a federal Lorazepam is a medication that is often prescribed to help manage anxiety in dementia patients. Lastly, ongoing studies are proposing virtual reality-related approaches that include music, sensory, and mental stimulations to improve cognitive functions (attention, executive function, visual and verbal memory) and psychological domains (agitation, depression, anxiety, and apathy) (8789). Anticonvulsants, such as carbamazepine, gabapentin, and pregabalin, may be useful in patients who did not respond to antipsychotics, although clear evidence is lacking (118120, 179). Before In contrast, the Managing Agitation and Raising Quality of Life (MARQUE) intervention (74) has failed to improve agitation prevention in care home settings. PDF BEHAVIORAL Care Brief DEMENTIA in LBD - Lewy body A total of 11 studies met inclusion criteria, and all were in patients with mental and behavioral disorders. Bianchetti A, Rozzini R, Guerini F, Boffelli S, Ranieri P, Minelli G, et al.. Clinical presentation of COVID19 in dementia patients. In recent days, the global pandemic has increased agitation incidence among dementia patients and generated higher distress levels in patients and caregivers. The use of citalopram is supported by the most compelling evidence for treating AD dementia-related agitation (156).