Is there a role for antipsychotic use in dementia?

Contributed by: Nadeem Bhanji, MD, FRCP(C)

Introduction

The rapid growth of Canada’s and the developed world’s aging populations has been accompanied by a commensurate increase in the rate of elderly with dementias.

Unfortunately, there are no treatments available that truly prevent or delay dementing illnesses. With each passing decade, increasing numbers of individuals will be diagnosed with dementias, as aging is one of the identified risk factors for illness. Alzheimer’s and vascular dementias are the two most common forms of dementia in the aging population.

At all stages of the dementia, non-cognitive symptoms may overlap with cognitive changes. For example, in the initial period before diagnosis, memory changes may be preceded by neuropsychiatric syndromes such as personality change or development of depressive or anxiety symptoms. As the dementia progresses, there may be other developments that result in further emotional problems, such as loss of driving or other autonomy, loss of partner and supports, and so on. Emergence of behavioral problems as the disease progresses is often the proverbial last straw that results in placement in long-term care.

Examples of behavioral symptoms that can occur at any time of dementia include, but are not limited to:

• Apathy
• Mood changes
• Argumentativeness/stubbornness
• Agitation/aggression
• Hallucinations (both visual and auditory)/mis-identification syndromes
• Day-night reversal

Many of the above symptoms of dementia can be aggravated by sensory loss; therefore, prompt and effective treatment of sensory loss (such as hearing aids or vision correction) can help optimize the person’s symptoms and quality of life.

Despite the goal of optimizing sensory modalities (e.g., attending seniors’ day programs, use of aromatherapy, etc.), behavioral symptoms may continue as the dementia progresses and evolves. There may still be behavior problems that challenge individuals and their families, prompting families to request pharmacological interventions.

Consider the following case example.

Case Study

Amira, 72, is a patient with a documented history of dementia (likely Alzheimer’s-related) who has been living with her daughter. Over the five years since her initial diagnosis and follow-up, her dementia appears to have progressed to an advanced stage. As Amira is illiterate, formal cognitive testing could not be performed using the Mini-Mental State Examination or the Montreal Cognitive Assessment screen. However, the Roland Universal Dementia Assessment Screen (RUDAS) was attempted, with results indicating a drop in score from 13/30 (five years ago) to 7/30 (now).

In addition to both short-term and long-term memory problems documented with the RUDAS, Amira is reportedly demonstrating significant behavioral symptoms related to the dementia. Symptoms as noted by her family include: sun-downing (whereby she becomes hypervigilant in the evening and more anxious, repeatedly waking up her grandchildren at 2 a.m. to get “ready for school”); pacing about the house; recalling and re-experiencing traumatic memories from the past (she was in a war-torn country, where her life was in indirect danger and two of her sons were murdered); hoarding partially-eaten, hidden and forgotten food in her bedroom; and emerging hallucinations (e.g., calling out to her deceased children as if they are in the house).

Management

Amira’s daughter would like to hire professional care for her but the idea of placement does not appeal to the family and does not align with their culture and tradition. Amira’s daughter is conflicted and desperate, as Amira’s behavior symptoms are having a negative effect on her grandchildren. In terms of management, Amira’s ideal treatment would incorporate both pharmacological and non-pharmacological interventions.

Non-pharmacological interventions may be easy to identify but require patience and persistence in application. For instance, having a reliable caregiver – who preferably can speak the patient’s language – regularly come to the home in the evening to spend a few hours with Amira would be ideal. This would provide much-needed respite to the family, particularly Amira’s daughter. Often, caregivers with experience and familiarity with dementia are available through homecare services. The initial period of adaptation can be challenging for all parties (e.g., Amira may feel threatened to see an unfamiliar person in the house). Pause for thought: What other non-pharmacological interventions could be employed in this case?

With respect to pharmacological strategies, there are fairly limited options available and the patient has exhibited poor tolerability (diarrhea) with cholinesterase inhibitors in the past. Given that the patient has an advancing dementia, as well as re-emergence of post-traumatic distress symptoms (i.e., re-experiencing the trauma of having lost two sons in the war), Amira may benefit from use of some psychotropic agents.

Antidepressants such as citalopram or escitalopram may be used off-label to help with agitation, especially if there are comorbid mood symptoms. However these agents are not devoid of side effects, such as gastrointestinal distress, prolongation of the QTc interval or the development of hyponatremia. Additionally, there may be other factors to consider when prescribing these agents, including drug interactions or pill burden. Antidepressants tend to work slowly, which may not help the person in the immediate stage of suffering. Alternatively, or in conjunction, antipsychotic agents may act more quickly to decrease distress in the patient and their families.

Bearing all this in mind, a 6.25 mg dose of quetiapine was prescribed for use when Amira was severely agitated. The instructions to her family were that no more than 25 mg per day was to be given in divided doses (up to four times per day, maximum) to help with the agitation. Prior to the prescription, risks and benefits of this medication were explained, such as the increased morbidity and mortality (falls, strokes, MI and death) associated with this category of medication. Amira’s daughter agreed to use the lowest dosage possible and to keep the physician informed while looking for additional caregivers for Amira.

Discussion

Drug trials have shown that risperidone has a reasonably significant beneficial effect on aggression and to a lesser extent, psychosis, for people with Alzheimer’s disease. These effects are seen when the drug is taken for a period of 6–12 weeks. Accordingly, risperidone has been approved by Health Canada for the short-term management of behavioral symptoms in dementia.

Because not all dementia symptoms respond to antipsychotic agents, other antipsychotic treatments could be considered. For instance, persons with Lewy body dementia (dementia with Lewy bodies or Parkinson’s disease dementia) respond better to quetiapine or clozapine, as they are very sensitive to risperidone or other antipsychotic agents. Similarly, aripiprazole is a safer option for patients with prolonged QTc interval Regardless of the antipsychotic agent chosen, it should be done with the utmost care, under supervision and with regular review.

As previously noted, some behavioral and psychological symptoms, such as distress and anxiety during personal care, restlessness or wandering, may not be helped by antipsychotic drugs. These symptoms need a more tailored approach, often requiring knowledge of the individual’s personal preferences and an emphasis on non-pharmacological strategies. For people with mild-to-moderate behavioral symptoms of any kind, the National Institute for Health and Care Excellence recommends that antipsychotic drugs should not be prescribed in instances of distress, anxiety, restlessness or wandering. Non-drug approaches remain the strong preference for managing these types of distressing but non-harmful symptoms.

Conversely, people with severe psychotic or aggressive symptoms may respond better to antipsychotic drugs as opposed to non-drug approaches. Symptoms may be considered severe enough in this regard if they put the person or others around them at risk, or if the symptoms are occurring frequently or are causing a great deal of distress, e.g., Amira’s disconcerting hallucinations as she re-experienced the murder of her sons. If severe symptoms include behaviors such as physical aggression pose a risk of harm to the person or others around them, antipsychotic agents may be required. Frequent monitoring and communication with family and caregivers is prudent and essential, when using antipsychotic drugs.

Summary and Conclusion

With the increase in our aging populations, the need for improvements in dementia care is essential. The increase in dementia growth puts both patients and their families in challenging situations as they strive to safely manage and care for the loved one affected by the illness without overwhelming the family and caregivers. Many dementia symptoms do not respond to traditional pharmacological treatments and require knowledge of the patient’s preferences as well as awareness of non-pharmacological strategies.

Addressing and treating sensory losses can help ameliorate many of the behavior symptoms. A hearing assessment can lead to better participation in family gatherings and thus decrease apathy. Conversely, where non-pharmacological strategies do not appear adequate, there may be a role for pharmacological strategies. As an example, recurrence of anxiety symptoms may be aided by serotonergic agents.

Antipsychotic agents may be used selectively in situations where aggression, hallucinations and distressing symptoms arise, and after discussion of their mode of use with families and patients with dementia.

Although risperidone is the only antipsychotic agent approved for short-term use in managing dementia-related behavior symptoms, other antipsychotic agents may play a selective role in short-term management of the dementia. Finally, behavior symptoms tend to be transient, so reassessment with a goal of tapering off the antipsychotic medication is always prudent practice.

References

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4. Ballard C, Aarsland D, Francis P et al. Neuropsychiatric Symptoms in Patients with Dementias Associated with Cortical Lewy Bodies: Pathophysiology, Clinical Features, and Pharmacological Management. Drugs & Aging 2013; 30(8):603–611.
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6. National Institute for Care and Health Excellence. Low-dose antipsychotics in people with dementia. https://www.nice.org.uk/advice/ktt7 Accessed on 12 Oct 2017