Gender, aggression and serotonergic function are associated with response to sertraline for behavioral disturbances in Alzheimer's disease, The efficacy of mirtazapine in agitated patients with Alzheimer's disease: a 12-week open-label pilot study. A 2018 meta-analysis examining medications used to alleviate agitation in all types of dementia included 36 RCTs with a total of 5,585 participants (mean age = 81.8 years 4.9 years; 69.1% female).1 The primary outcome was a 50% reduction in baseline agitation at eight weeks. The CATIE-AD study evaluated the effects on NPS of olanzapine, risperidone, and quetiapine, compared with placebo. Promising therapies for the treatment of frontotemporal dementia clinical phenotypes: from symptomatic to disease-modifying drugs, Neurotransmitter deficits from frontotemporal lobar degeneration. After the first cases of the novel coronavirus disease 2019 (COVID-19) were reported in Wuhan, China, in December 2019, the spread of SARS-CoV-2 rapidly became a pandemic, involving millions of patients worldwide. Finally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be a precipitating factor for agitation because of the related long-term hospitalization and quarantine (4244) or the ensuing viral encephalitis, critical illness encephalopathy, and systemic inflammation (45). Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: a randomised, controlled trial with trazodone. -9-tetrahydrocannabinol (THC) (132), dronabinol, and nabilone are the most widely investigated cannabinoid receptor agonists in clinical trials (222). Sloane PD, Hoeffer B, Mitchell CM, McKenzie DA, Barrick AL, Rader J, et al.. Effect of person-centered showering and the towel bath on bathing-associated aggression, agitation, and discomfort in nursing home residents with dementia: a randomized, controlled trial. Neuropsychiatric symptoms in Alzheimer disease, vascular dementia, and mixed dementia. Sampson EL, Raven PR, Ndhlovu PN, Vallance A, Garlick N, Watts J, et al.. A randomized, double-blind, placebo-controlled trial of donepezil hydrochloride (Aricept) for reducing the incidence of postoperative delirium after elective total hip replacement, Donepezil for anticholinergic drug intoxication: a case report. All Rights Reserved. The symptom also represents a management challenge for clinicians. The Overt Agitation Severity Scale (OASS) offers a helpful approach to detect and rate agitation when spanning from anxiety to aggression (56). The richmond agitation-sedation scale: validity and reliability in adult intensive care unit patients. The compound is FDA-approved for treating schizophrenia and major depressive disorder as add-on therapy (217). Few data, including mainly case reports and small case series, are available for other anticonvulsants (gabapentin, levetiracetam, topiramate, and lamotrigine) (115). -. Here are some examples of side effects commonly reported with Ativan injections and Ativan tablets: dizziness. Selective serotonin reuptake inhibitors (SSRIs) and risperidone (Risperdal) are moderately effective at decreasing agitation in all types of dementia. The usual range is 2 to 6 mg/day given in divided doses, the largest dose being taken before bedtime, but the daily dosage may vary from 1 to 10 mg/day. sleepiness, which can be mild or excessive . For instance, the drug may induce QT prolongation (216). Several studies have considered agitation as indicative of the external expression of anxiety (68). No use, distribution or reproduction is permitted which does not comply with these terms. All authors agree to be accountable for the content of the work. Dementia is very common in patients with Parkinson's Disease, and is most likely to be of dementia with Lewy bodies (DLB) pathology or may be of Alzheimer's Disease pathology. Patients treated with citalopram had fewer falls than those treated with olanzapine (OR = 0.81; 95% CI, 0.68 to 0.91; P = .012), less orthostatic hypotension than those taking quetiapine (OR = 0.81; 95% CI, 0.68 to 0.97; P = .032) and olanzapine (OR = 0.80; 95% CI, 0.66 to 0.95; P = .020), and fewer hospitalizations than those who were given quetiapine (OR = 0.92; 95% CI, 0.88 to 0.95; P = .016) and olanzapine (OR = 0.78; 95% CI, 0.64 to 0.92; P = .004). Another RCT also demonstrated that citalopram decreases agitation scores compared with risperidone, without relevant side effects (107). Nevertheless, clinicians often liberally implement drugs used in other forms of dementia, even in the absence of evidence-based support. Furthermore, the direct assessment of unmet needs in hospitalized patients, which is often less recognized and identified than expected, can provide a more time-effective approach in a clinical environment, according to the standards of Needs-driven care (68) based on the Unmet Needs Model (80). Lorazepam ( Ativan) is a generic prescription medication used to treat anxiety in adults and children ages 12 years and older. Evaluation of delirium in critically ill patients: validation of the confusion assessment method for the intensive care unit (CAM-ICU). Glass OM, Hermida AP, Hershenberg R, Schwartz AC. official website and that any information you provide is encrypted Copyright 2021 Amore, D'Andrea and Fagiolini. All the strategies developed in the last 20 years have led to a sophisticated solution, the Delirium Room (DR) (99, 100). Age-related metabolic alterations include hypoalbuminemia, hepatic or renal failure, and dehydration, conditions that should not be overlooked. 2005;65(9):1207-22. doi: 10.2165/00003495-200565090-00003. Risperidone (odds ratio [OR] = 1.96; 95% CI, 1.49 to 2.59; number needed to treat [NNT] = 6) and SSRIs as a class (OR = 1.61; 95% CI, 1.02 to 2.53; NNT = 25) were more effective than placebo, although no individual SSRI reached statistical significance. Most trials generally found improvements across a variety of outcomes related to agitation, although there was some disparity if specific outcomes were considered. In case of an agitated state, neuroleptics represent the first choice, especially haloperidol (starting dose ranging from 0.5 to 1 mg, not to exceed from 3 to 5 mg in 24 h), which also presents the advantage of parenteral formulation (136, 137). Clozapine for treatment-resistant agitation in dementia. Caution: respiratory depression. Less commonly reported adverse effects include: Blood and lymphatic system disorders such as thrombocytopenia, leucopenia, agranulocytosis, and pancytopenia. . Adult 1-2 mg daily, to be taken at bedtime. Masopust J, Protopopov D, Vali M, Pavelek Z, Klmov B. In a clinical trial comparing dosage and time needed to reach a therapeutic response of three antipsychotics (risperidone, sulpiride, and quetiapine), the risperidone-treated group showed the shortest time to obtain a clinical response (172). Nevertheless, some anecdotal evidence has indicated the efficacy and safety of atypical neuroleptics. Kales HC, Lyketsos CG, Miller EM, Ballard C. Management of behavioral and psychological symptoms in people with Alzheimer's disease: an international delphi consensus. 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. and transmitted securely. Three placebo-controlled studies on donepezil in PDD patients (120122) produced no effects vs. placebo for psychiatric disturbances. Reus VI, Fochtmann LJ, Eyler AE, Hilty DM, Horvitz-Lennon M, Jibson MD, et al.. Olanzapine (Zyprexa) and risperidone reduce dementia-related agitation much longer than placebo. Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement) (66). Findings from a pilot randomised controlled trial, Implementation of a baby doll therapy protocol for people with dementia: innovative practice. official website and that any information you provide is encrypted Received 2020 Dec 20; Accepted 2021 Mar 12. Durn JC, Greenspan A, Diago JI, Gallego R, Martinez G. Evaluation of risperidone in the treatment of behavioral and psychological symptoms and sleep disturbances associated with dementia, Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials, Comparative efficacy of risperidone versus haloperidol on behavioural and psychological symptoms of dementia. 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. hyper- or hypoglycemia, electrolyte disturbance, renal or hepatic Any pharmacological treatment for agitation in hyperkinetic delirium should be started at the lowest dose and continued for the minimum amount of time (134). IM lorazepam due to the risk of respiratory depression. Further suggestions for pharmacological management of acute agitation, such as agitation in delirium and chronic agitation in dementia, are depicted in the following sections. It should, therefore, no longer be used as monotherapy. Despite earlier studies not focusing on agitation effects, in the first RCT, citalopram and perphenazine were more effective than placebo in short-term hospital treatments of psychotic disturbances, including agitation (106). Over the past years, several studies have investigated a wide range of non-pharmacological approaches to treat and prevent dementia-related agitation. 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. 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. 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. Vital signs monitoring is mandatory to manage life-threatening conditions, such as cardiocirculatory or respiratory failure. Indeed, this drug mainly acts through direct serotonin receptor blockade and may produce sedation due to its strong histaminergic effects (149). Your doctor may adjust your dose as needed. Characterizing PRN Use of Psychotropic Medications for Acute Agitation in Canadian Long-Term Care Residents with Dementia Before and During COVID-19. The overt agitation severity scale for the objective rating of agitation. Ten patients with Alzheimer's disease and ten age-matched normal controls were studied in a double-blind, placebo-controlled acute trial of 1 mg PO lorazepam to test the effects of low-dose benzodiazepine on memory and behavior in a mostly older population. These drugs can aid in managing anxiety symptoms like the following: Worry. 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. 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. The Agitated Behavior Mapping Instrument (ABMI) (59) is a diagnostic scale that evaluates 14 different physical and verbal agitated behavior features. AF is/has been a consultant and/or a speaker and/or has received research grants from Allergan, Angelini, Aspen, Boehringer Ingelheim, Daiichi Sankyo Brasil Farmacutica, Doc Generici, FB-Health, Italfarmaco, Janssen, Lundbeck, Mylan, Otsuka, Pfizer, Recordati, Sanofi Aventis, Sunovion, and Vifor. Benzodiazepines are central nervous system (CNS) depressants, which are medicines that slow down the nervous system. 18F-Fluorodeoxyglucose positron emission tomography cortical metabolic activity associated with distinct agitation behaviors in Alzheimer disease, Maintaining internal representations: the role of the human superior parietal lobe. Considering that the serotonin 5-HT2AR polymorphisms and altered functioning of these receptors are associated with psychosis and aggressiveness onset in AD patients, recent studies have been focused on the effects of pimavanserin, a selective inverse agonist of the 5-HT2AR (212) or lumateperone and brexpiprazole, two novel atypical antipsychotics acting as 5-HT2A antagonists. The use of citalopram is supported by the most compelling evidence for treating AD dementia-related agitation (156). Nowadays, dementia-related agitation treatments pose a significant challenge to clinicians as specific pharmacological therapies are lacking. Thus, further investigation and research are required. In FTD, even though the data are still controversial, agitation appears to be related to increased dopaminergic transmission (31). Goyer PF, Andreason PJ, Semple WE, Clayton AH, King AC, Compton-Toth BA, et al.. Positron-emission tomography and personality disorders. doi: 10.1002/14651858.CD004770.pub3. Accessibility 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. Moreover, as previously reported, patients with dementia, when hospitalized, often present with a more complex clinical picture of hyperkinetic delirium (42). In this extension study, three different dextromethorphan doses are administered twice a day over 52 weeks. Considering this limitation, as well as the lack of recent studies addressing the issue of agitation in VaD, we report the most relevant approaches identified. Cognitive effects differed somewhat between Alzheimer patients and normal . Nabilone appeared to be the most promising and was reported to reduce agitation in a randomized, double-blind, placebo-controlled crossover trial ({"type":"clinical-trial","attrs":{"text":"NCT02351882","term_id":"NCT02351882"}}NCT02351882), although patients experienced significant sedation (133). Ativan (lorazepam) and Xanax (alprazolam) belong to the benzodiazepine class of drugs. The figure depicts the cerebral areas involved in the pathological process of agitation. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). The phase IV clinical study analyzes which people take Ativan and have Agitation. 5 Historically, lorazepam has been clinically used as an antianxiety agent for acute or chronic anxiety, as a . Aarsland D, Laake K, Larsen JP, Janvin C. Donepezil for cognitive impairment in Parkinson's disease: a randomised controlled study. The application of combined stimuli (tasks, reading, work-related, manipulation) has shown to be more effective than a single activity (81). Griffin CE III, Kaye AM, Bueno FR, Kaye AD. A 2017 RCT with 75 nursing home residents who had Alzheimer-type dementia and were 60 years or older at diagnosis measured the effectiveness and safety of citalopram (30 5.8 mg per day) relative to quetiapine (Seroquel) and olanzapine, with 25 patients per group.3 The interventions were equally effective in treating agitation in patients with Alzheimer-type dementia and citalopram was associated with fewer adverse outcomes than quetiapine and olanzapine. Evidence summary [ESUOM41] Published: 10 March 2015. Dextromethorphan was deuterated to improve its pharmacokinetic profile and reduce its first-pass metabolism in the liver (221). Executive dysfunction in Alzheimer's disease: association with neuropsychiatric symptoms and functional impairment. Huang CL, Hwang TJ, Chen YH, Huang GH, Hsieh MH, Chen HH, Hwu HG. Intramuscular olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of acute schizophrenia with agitation: An open-label, randomized controlled trial. Brexpiprazole is a second-generation antipsychotic, occasionally referred to as a third-generation antipsychotic with partial agonist properties at the D2 receptor. Moyle W, Murfield J, Jones C, Beattie E, Draper B, Moyle W, et al.. Can lifelike baby dolls reduce symptoms of anxiety, agitation, or aggression for people with dementia in long-term care? Cohen-Mansfield J, Dakheel-Ali M, Marx MS, Thein K, Regier NG. In a nursing home setting, a longitudinal 6-month study showed similar efficacy against agitation of citalopram, olanzapine, or quetiapine, even though citalopram was associated with a lower occurrence of falls, orthostatic hypotension, and fewer hospitalizations (109). Antipsychotic use in people with dementia with Lewy Bodies is associated with increased mortality. Accessibility 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. Dextromethorphan/quinidine (Nuedexta) may be effective at reducing agitation in patients with dementia. 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. This notion has been supported by postmortem studies (12, 13) showing the large presence of neurofibrillary tangles in the OFC and ACC of patients with the frontal variant of AD. Particular attention and research endeavor should be put into the treatment of elderly patients. Devanand DP, Pelton GH, D'Antonio K, Strickler JG, Kreisl WC, Noble J, et al.. Low-dose lithium treatment for agitation and psychosis in alzheimer disease and frontotemporal dementia, Gabapentin in geriatric psychiatry patients. Assessment and management of agitation in psychiatry: expert consensus. A mGluR2 agonist, LY2979165, is not investigated in one phase II clinical trial. 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). Although risperidone revealed efficacy earlier, the drug produced a higher burden of side effects (110). 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). Cagnin A, Di Lorenzo R, Marra C, Bonanni L, Cupidi C, Lagan V, et al.. Behavioral and psychological effects of coronavirus disease-19 quarantine in patients with dementia, Delirium in COVID-19: a case series and exploration of potential mechanisms for central nervous system involvement, Altered mental status in older patients in the emergency department, Behavioral emergencies: special considerations in the geriatric psychiatric patient, Approach to the agitated emergency department patient, Efficacy and tolerability of benzodiazepines for the treatment of behavioral and psychological symptoms of dementia: a systematic review of randomized controlled trials, Prevention, diagnosis, and management of serotonin syndrome. For oral dosage form (extended-release capsules): For anxiety: AdultsOne capsule once a day in the morning. Lorazepam is an antidepressant generally used to treat anxiety. 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. An official website of the United States government. However, the Confusion Assessment Method for the ICU (CAM-ICU) is a more sensitive and specific assessment to diagnose a delirium state (65). (SOR = A, based on meta-analysis.) 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. Another randomized double-blind study (Ancill et al., 1991) compared the daily oral administration of alprazolam with lorazepam in dementia inpatients with agitation. Pharmacological management of acute agitation. Bellelli G, Morandi A, Davis DHJ, Mazzola P, Turco R, Gentile S, et al.. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. With an overall prevalence of about 30%, agitation is the third most common neuropsychiatric symptoms (NPS) in dementia, after apathy and depression, and it is even more frequent (80%) in residents of nursing homes. Diagnosis and management of dementia with lewy bodies: fourth consensus report of the DLB consortium. FOIA 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. No FDA-approved therapies are available for FTD (174). Delli Pizzi S, Franciotti R, Tartaro A, Caulo M, Thomas A, Onofrj M, et al.. Available online at: Zeller SL, Rhoades RW. To facilitate this, 0.5 mg, 1 mg, and 2 mg tablets are available. Answers are drawn from an approved set of evidence-based resources and undergo peer review. 2021 Feb 22;12:628965. doi: 10.3389/fpsyt.2021.628965. Cochrane Database Syst Rev. Lorazepam overview. . Jeste D V, Blazer D, Casey D, Meeks T, Salzman C, Schneider L, et al.. ACNP white paper: update on use of antipsychotic drugs in elderly persons with dementia, Quetiapine for the treatment of behavioural and psychological symptoms of dementia (BPSD): a meta-analysis of randomised placebo-controlled trials, Antidepressants for agitation and psychosis in patients with dementia, Donepezil for vascular cognitive impairment, Rivastigmine for vascular cognitive impairment, Galantamine for vascular cognitive impairment, Cholinesterase inhibitors for lewy body disorders: a meta-analysis. 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. 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. Bonanni L, Di Giacomo R, D'Amico A, Frazzini V, Franciotti R, Manzoli L, et al.. Akinetic crisis in dementia with lewy bodies. Lin LW, Weng SC, Wu HS, Tsai LJ, Lin YL, Yeh SH. Rosen J, Burgio L, Kollar M, Cain M, Allison M, Fogleman M, et al.. Furthermore, blood hypoperfusion in the anterior temporal lobe (ATL), dorsolateral pre-frontal cortex (dlPFC), and superior parietal cortex (SPC) is thought to contribute to the production of abnormal emotional responses to external stimuli, thereby causing aggressive or agitated states. Nonetheless, not every PCC-based strategy is effective. See this image and copyright information in PMC. Side effects Common side effects of lorazepam include: sedation dizziness physical weakness or a lack of energy difficulties with coordination, speech, and balance respiratory depression, which.
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lorazepam for agitation in dementia
