This is the third article in a series on cognitive impairment and dementia in older people. The final article in the series will focus on palliative care for people with dementia. See side menu for other articles in the series.

Key practice points:

• Behavioural and psychological symptoms of dementia (BPSD) are often an attempt by the patient to communicate, therefore understanding why the behaviour or symptom is occurring is the key to management, e.g. are they in pain or frustrated by an aspect of their surroundings?
• Environmental and behavioural interventions should be considered first in patients with BPSD; an understanding of the patient’s previous vocation, interests, abilities, social and family roles, cultural background and spirituality helps to individualise interventions.
• Antipsychotic medicines have limited evidence of benefit for BPSD and are associated with significant risk. If an antipsychotic is required, it should be appropriate for the target behaviour requiring modification, and frequent monitoring of treatment response and adverse effects should occur. Trial withdrawal of the antipsychotic within three months, except in patients with long-term psychiatric illness, e.g. bipolar disorder.
• Antipsychotics should not be used as a routine method to sedate patients with dementia who are difficult to manage or as a routine alternative to benzodiazepines

Part 1: Understanding the symptoms and trialling non-pharmacological interventions

The term “Behavioural and Psychological Symptoms of Dementia (BPSD)” refers to the spectrum of non-cognitive and non-neurological symptoms of dementia, such as agitation, aggression, psychosis, depression and apathy.^{1, 2} At least 80% of people with dementia experience BPSD.² Depression and anxiety can be among the first symptoms of dementia, while other BPSD such as agitation and aggression more commonly occur later, especially as the person’s ability to communicate and influence their environment diminishes.³ These behaviours can be extremely stressful for the person and their family/whānau and carers, and are often a reason for people with dementia being admitted into residential care.² Appropriate treatment of BPSD can significantly improve the quality of life of the patient and their families.

Non-pharmacological approaches are the first-line intervention

There is concern that antipsychotics are over-prescribed to control behaviours in people with dementia that family, whānau or carers may find challenging.⁴ The first approach to managing BPSD is to try to understand why the behaviour is occurring, and, where possible, resolve these underlying factors.

Do you know who I am?

Having an understanding of the patient’s background can provide greater insight into the potential causes and solutions for BPSD, e.g. knowing their life story, their culture and religion/spirituality, their previous vocation, interests, routines, family/whānau role, sexuality and significant life events.³ It is also important to understand the nature of the relationship between the person with dementia and their carer and the stresses that the condition is placing on both.³

Individualise interventions and monitor the patient’s response

Although the evidence base for non-pharmacological treatments of BPSD is not strong, in part because person-centred treatment approaches are difficult to study, there are generally fewer risks associated with these interventions and they should always be considered first. Non-pharmacological interventions should be tailored to the individual patient and the target behaviour(s) and the response monitored.

Identify target behaviours

Managing BPSD requires a targeted approach, i.e. focus on a specific behaviour or symptom and plan individualised interventions.

Identify the target symptoms or behaviours that require modification (Table 1) and document this in the patient’s notes, including the timing, frequency, pattern and severity.⁵ If a patient has numerous or severe BPSD consider quantifying them using a tool so the response to interventions can be more easily assessed (see: “Quantifying BPSD with a tool”). A request for a home risk assessment may be necessary to assess any danger the patient may present to themselves or others.³

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Table 1: Common presentations of frequently encountered BPSD and non-pharmacological management strategies^1-3

Assess for underlying causes and contributing factors

“Why is this behaviour occurring?”

Consider factors that may be causing or exacerbating the behaviour; Table 2 lists some common examples:

• Are the symptoms explained by another psychiatric condition such as depression or delirium?
• Is the patient taking any medicines that may be causing or contributing to the symptoms?
• Is the patient in otherwise good physical health? Is there a possibility of undetected pain (see: “Untreated pain may be a cause of BPSD”), infection, constipation or discomfort?
• Are there any factors in the patient’s living environment, i.e. their home/care facility, or unmet personal needs which may be exacerbating behaviours?

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Table 2: Factors that may cause or contribute to BPSD^3,7

Non-pharmaceutical interventions for patients with BPSD

Non-pharmacological treatments and interventions should be trialled first for managing BPSD.² There are limited clinical trials supporting non-pharmaceutical approaches, and due to variations in study design and methodology it is difficult to compare the efficacy of non-pharmacological treatments, however, there is a substantial body of clinical experience justifying this approach.⁷

Once a non-pharmacological intervention has been introduced, the patient should be monitored to determine the effect of the intervention.³ An assessment tool may be useful for this; see: “Quantifying BPSD with a tool”.

Environmental interventions to prevent BPSD

Problems in the physical surroundings and amenities of the patient’s home or residential care facility can cause or exacerbate restlessness, frustration, anxiety and disorientation. Changes that could be discussed with the patient’s carer, family/whānau or residential care manager may include:¹

• Reducing levels of noise and negative distraction, e.g. television at high volume
• Setting an ambient temperature and considering the patient’s proximity to heaters or cold drafts
• Ensuring adequate lighting, avoiding glare from artificial light or sunlight
• Using labels and memory aids for objects the patient frequently uses
• Ensuring easy access to the toilet – regular prompting can help, signage may be appropriate
• Providing privacy and avoiding over-crowding, e.g. from groups of visitors to the home or other residents in a care facility
• Having a prominent clock, calendar and daily schedule to improve orientation to time and to prompt activity
• In residential care facilities, make the patient’s surroundings as “home-like” as possible with personal belongings, pictures, photos and items of cultural significance
• Having consistent carers, where possible

Behavioural interventions to reduce BPSD

Specific behavioural interventions for BPSD will depend on the target behaviour that requires modification (Table 1). In general, encourage people with dementia to participate in activities that they find enjoyable and meaningful and are appropriate to their level of function, e.g. board games, cards, console games, artwork, craftwork, kapa haka or Kaumātua group, spectating or participating in sport, listening to music, using exercise equipment, supervised walking, social groups, interaction with animals.²

Local branches of Alzheimers New Zealand or Dementia New Zealand organise group activities: www.alzheimers.org.nz and www.dementia.nz

Age Concern provide an accredited visiting service where a younger person may visit an older person for approximately an hour each week: www.ageconcern.org.nz

Structured therapies

There is some evidence that structured interventions including music therapy, cognitive behavioural therapy and sensory therapy are beneficial for managing some BPSD including apathy, agitation, vocally disruptive behaviour, depression and anxiety.³ Enquire with your local DHB or PHO as to the availability of specialised therapy services for patients with dementia.

Part 2: Pharmacological interventions for patients with BPSD

Pharmacological interventions have a limited role in the management of BPSD as they are associated with a range of serious adverse effects in older people and the indications for which they are effective is relatively limited.⁹

Medicines for BPSD should be:^{1, 3, 9–11}

• Prescribed for target symptoms or behaviours for which there is evidence of effectiveness, i.e. they should not be used for other indications or to sedate patients who are difficult to manage
• Only considered once potentially reversible causes have been excluded and non-pharmacological interventions have been trialled; unless there is an immediate risk to the patient or others, or the patient is very severely distressed
• Always used in combination with non-pharmacological interventions
• Only initiated after informed consent has been obtained (and documented) from the patient or their legal representative
• Initiated as a trial and not prescribed indefinitely without need; review response to treatment, dose and adverse effects at least every three months
• Routinely withdrawn, slowly, after three months of improved symptoms unless symptoms were severe or due to a co-morbid psychiatric disorder, e.g. bipolar disorder or major depression; this is often possible without symptom re-emergence
• Re-started at the lowest effective dose, if symptoms return following a withdrawal, and schedule a further trial withdrawal in three to six months

Acetylcholinesterase inhibitors may be beneficial in mild to moderate dementia

Acetylcholinesterase inhibitors may be considered in people with Alzheimer’s-type dementia, vascular dementia where subcortical ischaemic changes are prominent and dementia associated with Parkinson’s disease/Dementia with Lewy Bodies (unapproved indication).¹² Donepezil (funded), rivastigmine (transdermal patch funded with Special Authority approval) or galantamine (not funded) may improve apathy, delusions and hallucinations, and less commonly improve aggression, depression, disinhibited behaviours, irritability or nocturnal disruption in patients with mild to moderate dementia.^{3, 7} There are a range of potentially significant adverse effects associated with acetylcholinesterase inhibitors, including gastrointestinal and neurological symptoms and bradycardia.

For further information on prescribing acetylcholinesterase inhibitors, see: “Recognising and managing early dementia”

Selective serotonin reuptake inhibitors for depression, anxiety or agitation

Selective serotonin reuptake inhibitors (SSRIs) are effective for the management of depression and anxiety in people with dementia that cannot be managed by non-pharmacological interventions alone.³ For people with Alzheimer’s disease, citalopram has been shown to reduce agitation, thereby causing less caregiver distress.¹³ There is also evidence that citalopram may improve other symptoms of BPSD, such as delusions, suggesting it may have antipsychotic effect.¹⁴ A two-month trial of citalopram may be considered, although the dose-dependent risk of increased QT-prolongation and worsening cognition needs to be balanced against the benefit of treatment.^{2, 13}

Tricyclic antidepressants should generally not be prescribed to patients with dementia as the anticholinergic effects may further disrupt cognition.²

Antipsychotics for aggression, delusions and hallucinations

Antipsychotics are only appropriate for patients with BPSD if aggression, agitation or psychotic symptoms are causing severe distress or an immediate risk of harm to the patient or others or if the patient has a pre-existing, co-morbid mental illness where antipsychotics are indicated.¹⁵

Antipsychotic medicines are only modestly effective in managing BPSD, and the level of effectiveness varies between patients. Antipsychotics are unlikely to be beneficial for wandering, calling out, social withdrawal or inappropriate sexualised behaviour in people with dementia.^{1, 16} They are also less likely to be effective for intermittent but challenging behaviours that are closely related to clear environmental triggers, e.g. aggression that only occurs during personal cares.

Even short courses of antipsychotics can cause significant adverse effects in people with dementia, e.g. sedation, increased risk of falls, extrapyramidal effects, pneumonia, stroke, cardiovascular events and increased mortality (see: “Stroke and mortality risk with antipsychotic medicines”), therefore the potential benefit of treatment needs to be weighed against the risks and discussed with the patient or their representative.¹⁵

Antipsychotics should be avoided in patients with Lewy body dementia or Parkinsons disease with dementia, as they can cause severe adverse reactions, particularly extrapyramidal symptoms.² Specialist advice should be sought before initiating an antipsychotic for these patients; quetiapine, aripiprazole or clozapine may sometimes be indicated.

Selecting an antipsychotic medicine

Risperidone and haloperidol are currently the only antipsychotics approved for use in BPSD in New Zealand.¹⁵ However, haloperidol is not a first-line choice due to increased adverse effects compared to atypical antipsychotics; it is, however, still used for the treatment of delirium in some patients with dementia.⁷ Other atypical antipsychotics such as olanzapine and quetiapine are not approved for the treatment of BPSD and treatment is off label; written consent should be obtained following a discussion of the risks and benefits of treatment.^{1, 15}

It is not possible to definitively recommend a single, safest and most effective antipsychotic medicine for BPSD.¹⁸ The patient’s co-morbidities, other medicines and the adverse effect profile of the medicine (Table 3) are used to determine the most appropriate treatment option. Risperidone is usually trialled first as it has strong evidence of effectiveness for BPSD, including psychosis, agitation and aggression.^{2, 15} It may also be less sedating than other antipsychotics, and therefore associated with a lower risk of falls.¹⁸

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Table 3: A comparison of the adverse effect profile of atypical antipsychotic medicines most commonly prescribed to older patients with BPSD^{19–22 *}

^* Antipsychotics are associated with a wide range of adverse effects, some of which, e.g. hyperprolactinaemia and dyslipidaemia, may be less relevant to older patients. A more extensive list of adverse effects is available from: https://bpac.org.nz/BPJ/2013/December/dementia.aspx

^† See: “Stroke and mortality risk with antipsychotic medicines”

Fewer studies have been conducted on other atypical antipsychotics

There is moderate evidence that aripiprazole is effective for the treatment of aggression and agitation in people with BPSD, but not psychosis.²

There is currently insufficient evidence to support the use of the newer atypical antipsychotics, amisulpride and ziprasidone for the treatment of older patients with BPSD.

Start low, go slow, with frequent monitoring

Antipsychotic medicines for the management of BPSD should be initiated as a trial and should not be prescribed indefinitely; treatment should ideally not exceed three months.¹⁵ Initiate at the lowest dose likely to provide therapeutic benefit (Table 4), e.g. half the adult dose or less, depending on body weight, co-morbidities and concurrent medicine use.¹⁶ Consider timing the dose in relation to the target behaviour, e.g. lunchtime for patients with agitation in the late afternoon.

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Table 4: Recommended starting and maintenance doses for antipsychotic medicines in older people with dementia¹⁶

Monitor patients during treatment and reduce dosing where possible

Prior to initiating an antipsychotic the patient’s body weight, blood pressure and HbA_1c should be recorded so changes can be compared to baseline.¹⁶ An ECG may be needed in patients at high cardiovascular risk to record their QT interval and monitor for any significant rise with treatment.¹⁶

The adverse effects associated with antipsychotics are generally dose-related and the risk can be minimised by regularly reviewing treatment, reducing the dose where possible and withdrawing treatment once the target behaviour is well-controlled.¹⁶

Close monitoring is required, especially in patients who are taking medicines with the potential for interactions with antipsychotics, including for:¹⁶

• Central nervous system depression, including sedation, increased confusion or cognitive impairment. Benzodiazepines, zopiclone, opioids, antihistamines, anticholinergic medicines of any kind, anti-Parkinson medicines and alcohol may exacerbate these symptoms and can also precipitate delirium.
• Peripheral anticholinergic effects, including dry mouth, constipation, urinary retention and blurred vision. Tricyclic antidepressants, opioids, oxybutynin and many other anticholinergic medicines may exacerbate these symptoms.
• Postural hypotension, dizziness and falls risk. Antihypertensives, benzodiazepines, zopiclone and antidepressants may exacerbate these symptoms.
• Extrapyramidal effects, including akathisia (restlessness), dystonia (abnormal facial and body movements), tardive dyskinesia (involuntary movements of tongue, face and jaw) and Parkinson symptoms (mainly akinetic-rigidity, but sometimes tremor)
• Metabolic changes, including weight gain, diabetes and hyperosmolar hyperglycaemic syndrome
• Infection, particularly urinary tract infections and aspiration pneumonia
• Deep vein thrombosis, pulmonary embolism and stroke

The medicine should be withdrawn immediately if significant adverse effects occur.¹⁵

A tool for estimating the anticholinergic burden of medicines in patients aged over 65 years is available from: www.acbcalc.com

Regularly review the need for antipsychotic medicines

Many patients with BPSD can be withdrawn from antipsychotics following three months of stable or improved behaviour.¹ In patients with severe symptoms it may be necessary to continue treatment long-term, e.g.:²¹

• When there are no alternative treatment options
• When the potential consequences of symptom relapse are unacceptably high
• When serious withdrawal symptoms have occurred in the past

If the patient does not respond to pharmaceutical treatment, confirm with their carer that they have been adherent to treatment and consider if the dose could be optimised and if treatment has continued for an adequate length of time, e.g. four to six weeks.^{16, 23} The antipsychotic should be withdrawn if there has been no improvement in the patient’s symptoms following this timeframe.⁵ If another antipsychotic is trialled, this should be done sequentially, rather than concurrently prescribing multiple antipsychotics.¹⁵

Withdraw antipsychotics gradually if treatment has been long-term

If a patient has been taking an antipsychotic long-term, e.g. for a year or more, the dose should be gradually tapered over weeks to months to prevent acute withdrawal and rapid symptom relapse.²³ The risk and potential severity of relapse is likely to be more severe in patients who have taken an antipsychotic for a long period or in those who have previously experienced a relapse following treatment withdrawal.²¹

In summary: assess the risk versus benefit carefully before prescribing antipsychotics

The increased risk of stroke, cardiovascular events and death associated with antipsychotic medicines in older people, and particularly those with dementia, is a significant clinical concern. It is currently unclear whether this risk is a class effect of if the risk is higher with specific medicines. What is certain is that the use of any antipsychotic medicine in people with dementia requires a careful risk versus benefit assessment. If it is decided that the patient is likely to benefit from an antipsychotic medicine, an appropriate consent process is essential, as is limiting the duration of pharmacological treatment to the minimum time period that is clinically necessary.