Neuropsychiatric Symptoms in Dementia: Considerations for Pharmacotherapy in the USA

Abstract

Dementia affects all domains of cognition. The relentless progression of the disease after diagnosis is associated with a 98% incidence of neuropsychiatric symptoms (NPS) at some point in the disease, including depression, psychosis, agitation, aggression, apathy, sleep disturbances, and disinhibition. These symptoms can be severe and lead to excess morbidity and mortality. The purpose of this article was to describe current literature on the medication management of NPS of dementia and highlight approaches to and concerns about the pharmacological treatment of NPS in the USA. Guidelines and expert opinion favor nonpharmacologic management of NPS as first-line management. Unfortunately, lack of adequate caregiver training and a high failure rate eventually result in the use of psychotropic agents in patients with dementia. Various psychotropic medications have been studied, although how they should be used in the management of NPS remains unclear. A systematic approach to evaluation, treatment, and monitoring, along with careful documentation and evidenced-based agent and dose selection, is likely to reduce risk and improve patient outcomes. Considerations should be given to the NPS presentation, including type, frequency, and severity, when weighing the risks and benefits of initiating, continuing, or discontinuing psychotropic management. Use of antidepressants, sedative/hypnotics, antipsychotics, and antiepileptic agents should include a clear and documented analysis of risk and benefit in a given patient with dementia.

COVID-19 Epidemic in Argentina: Worsening of Behavioral Symptoms in Elderly Subjects With Dementia Living in the Community

“…Sleep disturbances are frequent in AD patients and are related to age changes in sleep patterns, medication effects, comorbidity with anxiety, depression, and to the neurodegenerative disease by itself ( 18 ). Sleep disorders are disruptive to caregivers and increase the rate of institutionalization and caregiver burnout ( 22 , 23 ). Strategies to improve sleep quality include sleep hygiene, physical activity during the day, and keeping a structured daily routine ( 22 , 23 ).…”

“…Sleep disorders are disruptive to caregivers and increase the rate of institutionalization and caregiver burnout ( 22 , 23 ). Strategies to improve sleep quality include sleep hygiene, physical activity during the day, and keeping a structured daily routine ( 22 , 23 ). These strategies were all compromised during this lockdown period, and sleep difficulties were overall frequent, with even higher prevalence in subjects with mild dementia.…”

Current Understanding of the Neurobiology of Agitation

“… 41 – 44 However, there is limited efficacy in use of pharmacologic agents, and the side-effect profile needs to be carefully weighed against potential benefits. 40 For instance, atypical antipsychotics can lead to excess sedation, metabolic side effects, and EPS. In addition, a boxed warning from the FDA alerts prescribers to the increased risk of death associated with use of atypical antipsychotics in elderly patients with dementia-related psychotic symptoms.…”

“…Managing agitation in patients with dementia should be largely non-pharmacological, when possible, as there is an evidence base supporting a number of such interventions. 39,40 In Alzheimer dementia, in addition to the decline noted in cholinergic neurotransmission, the accumulation of amyloid plaques and neurofibrillary tangles may result in glutamatergic release, with potential for excitotoxicity. Available pharmacologic options include atypical antipsychotics (e.g., risperidone and olanzapine), antiepileptics (e.g., carbamazepine, gabapentin), serotonergic agents, and even less conventional options such as dextromethorphan/ quinidine combination, the latter possessing antiglutamatergic properties.…”

Pharmacologic Approaches for the Management of Apathy in Neurodegenerative Disorders

“…Moreover, conventional psychotropic drugs often overprescribed in AD, such as antipsychotics and Selective-Serotonin Reuptake Inhibitors (SSRI) antidepressants may increase levels of apathy in neurodegenerative disorders and may have overall insufficient effect to alleviate levels of BPSD (Anand et al, 2018). Weighing risks and benefits, it is recognized that psychotropic agents should be prescribed with caution in dementia (Azuar and Levy, 2018;Phan et al, 2019).…”