Mood stabilizers in Alzheimer’s disease: symptomatic and neuroprotective rationales (original) (raw)
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Progresses in treating agitation: a major clinical challenge in Alzheimer's disease
Expert opinion on pharmacotherapy, 2015
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. Areas covered: 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 literat...
Alternative pharmacological treatment options for agitation in Alzheimer’s disease
Geriatric Care, 2015
In patients with dementia and Alzheimer’s disease (AD), treatment of neuropsychiatric symptoms (NPS) is a major concern in the management of these devastating diseases. Among NPS in AD, agitation and aggression are common with earlier institutionalization, increased morbidity and mortality, and greater caregiver burden. Pharmacological treatments for AD-related agitation, specifically off-label use of atypical antipsychotics, showed only modest improvements, with increased side-effect burden and risk of mortality. Non-pharmacological treatment approaches have become the preferred firstline option. However, when such treatments fail, pharmacological options are often used. Therefore, there is an urgent need to identify effective and safe pharmacological treatments for agitation/aggression in AD and dementia. Unfortunately, progresses have been slow, with a small number of methodologically heterogeneous randomized controlled trials (RCTs), with disappointing results. However, evidence...
Alzheimer's & Dementia, 2019
INTRODUCTION-Alzheimer's disease (AD) is a disabling, common cause of dementia and agitation is one of the most common and distressing symptoms for patients with AD. Escitalopram for Agitation in Alzheimer's Disease (S-CitAD) tests a novel, clinically derived therapeutic approach to treat agitation in AD patients. METHODS-S-CitAD is a NIH-funded, investigator-initiated, randomized, multicenter clinical trial. Participants receive a structured psychosocial intervention (PSI) as standard of care. Participants without sufficient response to PSI are randomized to receive 15mg escitalopram/day or a matching placebo in addition to PSI. Primary outcome is the Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC). DISCUSSIONS -CitAD will provide information about a practical, immediately available approach to treating agitation in patients with AD. S-CitAD may become a model of how to evaluate and predict treatment response in patients with AD and agitation as a neuropsychiatric symptom (ClinicalTrials.gov Identifier:).
Citalopram for agitation in Alzheimer’s disease: Design and methods
Alzheimer's & Dementia, 2012
Background-Agitation is one of the most common neuropsychiatric symptoms of Alzheimer's disease (AD), and is associated with serious adverse consequences for patients and caregivers. Evidence-supported treatment options for agitation are limited. The citalopram for agitation in Alzheimer's disease (CitAD) study was designed to evaluate the potential of citalopram to ameliorate these symptoms.
Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial
JAMA, 2014
Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory. The primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease. Key secondary objectives examined effects of citalopram on function, caregiver distress, safety, cognitive safety, and tolerability. The Citalopram for Agitation in Alzheimer Disease Study (CitAD) was a randomized, placebo-controlled, double-blind, parallel group trial that enrolled 186 patients with probable Alzheimer disease and clinically significant agitation from 8 academic centers in the United States and Canada from August 2009 to January 2013. Participants (n = 186) were randomized to receive a psychosocial intervention plus either citalopram (n = 94) or placebo (n = 92) for 9 weeks. Dosage began at 10 mg per day with planned titration to 30 mg per day over 3 weeks based o...
Managing agitation in Alzheimer's disease and related disorders
Background: Alzheimer disease (AD) will affect increasing numbers of subjects as the population ages. Patients with AD and related disorders often develop agitation during the moderate to severe stages of their dementia. Agitation is often the reason that dementia patients need to be institutionalized. This review will address the natural history of agitation in AD, dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). It will also discuss the use of antidepressants, antipsychotic agents and anticonvulsant drugs in preventing and treating agitation in dementia patients.
The Journal of Prevention of Alzheimer's Disease, 2020
Dementia is characterized by a significant decline in one of several cognitive domains such as memory, language and executive function, affecting independence and representing a significant deterioration from a previous level of functioning (1). Alzheimer’s Disease (AD) represents the most common form of dementia and contributes up to 70% of the almost 50 million dementia cases worldwide, a number that is projected to double in 20 years (2).
JPAD, 2015
BACKGROUND The management of neuropsychiatric symptoms (NPS) such as agitation and aggression is a major priority in caring for people with Alzheimer's disease (AD). Agitation and aggression (A/A) are among the most disruptive symptoms, and given their impact, they are increasingly an important target for development of effective treatments. Considerable progress has been made in the last years with a growing number of randomized controlled trials (RCTs) of drugs for NPS. The limited benefits reported in some RCTs may be accounted for by the absence of a biological link of the tested molecule to NPS and also by key methodological issues. In recent RCTs of A/A, a great heterogeneity design was found. Designing trials for dementia populations with NPS presents many challenges, including identification of appropriate participants for such trials, engagement and compliance of patients and caregivers in the trials and the choice of optimal outcome measures to demonstrate treatment effectiveness. The EU/US-CTAD Task Force, an international collaboration of investigators from academia, industry, non-profit foundations, and regulatory agencies met in Philadelphia on November 19, 2014 to address some of these challenges. Despite potential heterogeneity in clinical manifestations and neurobiology, agitation and aggression seems to be accepted as an entity for drug development. The field appears to be reaching a consensus in using both agitation and aggression (or other NPS)-specific quantitative measures plus a global rating of change for agitation outcomes based on clinician judgment as the main outcomes.