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 well-established long-term interventions that are both effective and safe. While non-pharmacological interventions are the suggested first-line treatment, it isn’t effective in managing symptoms for every patient. In such cases, clinicians turn to the use of pharmacological interventions. Traditionally, these interventions consist of off-label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine and antidepressants, where the efficacy doesn’t necessarily outweigh the associated risks.

Areas covered: Gains made in understanding the neurobiological mechanisms underlying agitation have fueled several recent clinical trials. A comprehensive literature search for published articles evaluating pharmacologic interventions for agitation in AD was done. A review of some of these clinical trials was completed: dextromethorphan/quinidine, scyllo-inositol, brexpiprazole, prazosin, cannabinoids, dronabinol and citalopram show promise in treating agitation.

Expert opinion: Neurobiological findings and enhanced trial designs have re-ignited the area of pharmacological treatment of NPS. Although further research is needed to fully determine the safety, tolerability and efficacy of these treatments, the mission to finding effective treatments for NPS such as agitation in patients with dementia is well underway.

Keywords:

• agitation
• Alzheimer’s disease
• behavioral and psychological symptoms of dementia
• brexpiprazole
• cannabinoids
• citalopram
• dementia
• dextromethorphan/quinidine
• dronabinol
• neuropsychiatric symptoms
• pimavanserine
• prazosin
• psychosocial intervention
• scyllo-inositol
• treatment

Declaration of interest

A Porsteinsson reports receipt of a grant to his institution from AstraZeneca, Avanir, Baxter, Biogen, BMS, Eisai, Elan, EnVivo, Genentech/Roche, Janssen Alzheimer Initiative, Medivation, Merck, Pfizer, Toyama, Transition Therapeutics, the National Institutes of Health (NIH), the National Institute of Mental Health (NIMH), the National Institute on Aging (NIA) and the Department of Defense; paid consultancy for Elan, Janssen Alzheimer Initiative, Lundbeck, Pfizer and TransTech Pharma; membership on data safety and monitoring boards for Quintiles, Functional Neuromodulation and the New York State Psychiatric Institute; participation on a speaker’s bureau for Forest and development of educational presentations for CME Inc and PVI. 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.

Notes

This box summarizes key points contained in the article.