More than 5 million older adults in the United States are living with Alzheimer’s disease and other dementias. Although dementia is viewed as a memory loss disorder, neuropsychiatric symptoms (NPS) are common features. NPS can include aggression, agitation, wandering, depression, anxiety, sleep disturbance and paranoia. Nearly all patients with dementia will develop at least one NPS. These symptoms increase caregiver burden, escalate the cost of care and can lead to earlier institutionalization for some adults.
As providers, it is important to assess for NPS in patients with dementia. Reversible causes need to be ruled out and treated. These can include unidentified infections, particularly urinary tract infections; medication side effects; electrolyte imbalance; constipation; environmental triggers; and underlying psychiatric illness that predated the development of dementia. Even if the cause is irreversible, efforts to reduce patient suffering and improve quality of life can be made. For mild to moderate NPS, behavioral interventions might be helpful. For moderate-severe NPS, pharmacological interventions and behavioral interventions are often used simultaneously. Non-pharmacological interventions include: identifying triggers for agitation and aggression, modifying the environment where possible, and improving communication strategies.
The classes of medication that are used frequently to treat NPS include antidepressants, antipsychotics, and mood stabilizers. Depression can occur in 40% of patients with dementia and often presents as irritability, apathy and excessive crying. Verbally and physically aggressive patients who are also irritable, negative, socially withdrawn and appear dysphoric might benefit from an antidepressant trial. The serotonin agents are generally well tolerated in older adults and citalopram has some limited evidence that it is helpful for NPS.
Antipsychotic medications are sometimes used to treat psychosis (paranoia, hallucinations) and severe agitation in dementia. The atypical antipsychotics are generally better tolerated than the typical antipsychotics, which have a greater risk of anticholinergic side effects. There is an increased risk of stroke with the atypical antipsychotics, and an FDA Black Box warning was implemented about this risk on 2005. When considering this class of medication for an individual patient, a careful risk/benefit analysis is important, especially with patients with other cardiovascular risks. When looking at the relative risk, a patient with dementia has a 2% risk of dying from a stroke and a patient with dementia who is taking an antipsychotic medication has a 4% risk, which is double, but still relatively small. For any patient taking these medications, starting at the lowest possible dose, titrating slowly and using the medication for as short a time period of possible are important ways to reduce the risk of serious side effects. If an antipsychotic is being considered, quetiapine should be considered as a first line agent because it has low risk for extrapyramidal side effect, there is flexibility of dosing especially at low doses, and evidence shows a lower risk of mortality when compared with other antipsychotic medications. Symptoms that respond well to antipsychotic medications include hallucinations, paranoia, and agitation. The following symptoms generally do not respond well to this class of medication: wandering, social withdrawal, shouting, and cognitive defects. If the choice is made to start an antipsychotic medication, if there is no clinical response after 4 weeks of adequate dosing, it should be tapered off.
There is limited evidence for the effectiveness of mood stabilizer in NPS even though they are sometimes used to try to manage behavioral symptoms, especially if there are concerns about psychomotor activation, labile affect and rapid speech.
It is generally known that the cholinesterase inhibitors help slow down the progression of mild-moderate dementia and that the NMDA receptor agonist memantine helps slow down the progression of moderate-severe dementia. The effects of these medications on NPS has not been as well studied and there are no clear guidelines based on research or expert panels. There is some anecdotal evidence that there might be some benefit for some NPS and some randomized controlled trials used effect on NPS as a secondary outcome measure. What is challenging is to know which patients might derive some benefit from this class of medications and what specific symptoms might improve with these medications.
The goal of this e-weekly is to review the importance of assessing for neuropsychiatric symptoms in patients with dementia, as it is commonly co-morbid. If the cause of the NPS is reversible, it is important to address it to reduce suffering. Symptoms can be relieved with behavioral and pharmacological interventions and it is important to consider target symptoms when considering medication treatment, especially for the antipsychotic medications.