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

ABSTRACT

Introduction: Neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks safe and effective long term interventions. Nonpharmacological interventions are suggested as first-line treatment, but aren’t effective for every patient, resulting in pharmacological interventions for some patients, consisting of off-label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine, and antidepressants; where efficacy doesn’t necessarily outweigh associated risks.

Areas covered: Gains in understanding neurobiological mechanisms underlying agitation have fueled several recent clinical trials. This article updates our review published in 2014. Comprehensive literature search for published articles from January 2014 to December 2016 evaluating pharmacologic interventions for agitation in AD was done. A review of several clinical trials was completed: dextromethorphan/quinidine, scyllo-inositol, brexpiprazole, prazosin, cannabinoids, citalopram, escitalopram, pimavanserin, ITI-007, ORM-12741 show promise in treating agitation.

Expert opinion: Neurobiological findings, innovative trials designs, statistical approaches, and preliminary paths for regulatory agency acceptance have re-ignited the area of pharmacological treatment of NPS. Though further research is needed to fully determine the safety, tolerability and efficacy of these treatments, the mission to find effective treatments for neuropsychiatric symptoms such as agitation in patients with dementia is well underway.

KEYWORDS:

• Alzheimer’s disease
• dementia
• neuropsychiatric symptoms
• behavioral and psychological symptoms of dementia
• agitation
• treatment
• psychosocial intervention
• dextromethorphan/quinidine
• scyllo-inositol
• brexpiprazole
• prazosin
• cannabinoids
• dronabinol
• nabilone
• citalopram
• escitalopram
• pimavanserin
• ITI-007
• ORM-12741

Article highlights

• Individuals diagnosed with Alzheimer’s disease often experience Neuropsychiatric Symptoms in addition to cognitive impairment.

• Agitation is common among individuals with Alzheimer’s disease and is associated with earlier institutionalization, excess morbidity and mortality, greater health care use and caregiver burden.

• Use of psychosocial interventions may have a positive impact on both the patient and the caregiver, and are considered as first-line treatment for agitation in dementia. For the patients that do not adequately respond to non-pharmacologic interventions, a judicious pharmacologic intervention is indicated.

• Neurobiological research centered on the pathogenesis of agitation in AD has fueled a growing number of randomized controlled trials of drugs for agitation and other NPS.

• Several drugs have shown positive outcomes in clinical trials, hopefully establishing a new treatment paradigm for agitation in AD.

• It is likely that an approved medication for this indication will immediately impact practice in the field as there is a large commercial opportunity for medications that are safe, well tolerated and efficacious for NPS in dementia, including agitation.

This box summarizes key points contained in the article.

Declaration of interest

A Porsteinsson reports personal fees from Acadia Pharmaceuticals, Neurim Pharmaceuticals, Avanir, Biogen, Eisai, Grifols, Insys, Merck; grants to his institution from AstraZeneca, Eisai, Eli Lilly, Genentech/Roche, Merck, Toyama, NIA, NIMH, DOD, Avanir, Biogen; personal fees from Medscape, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded by any organization or entity.