what is being used to treat agitation in patient with dementia

The behavioural and psychological symptoms of dementia

The behavioural and psychological symptoms of dementia (BPSD) are divers equally symptoms of disturbed perception, thought, mood or behaviour in a person with dementia, which are non due to another major neuropsychiatric disorder, such equally a major depressive episode.¹ Well-nigh all people with dementia experience inappropriate behavioural and psychological symptoms at some point during their affliction. This can cause significant stress to family and caregivers and result in institutionalisation. As at that place is no cure for dementia, appropriate handling of BPSD can have a meaning bear on on the quality of life of the patient, their families and caregivers.

There is business organisation that antipsychotics are beingness over-prescribed to command inappropriate behaviour in people with dementia.ⁱⁱ The beginning approach to managing BPSD is to try to sympathise why the behaviour is occurring, and, where possible, command for these factors.

Although the testify base of operations for not-pharmacological treatments of BPSD is not strong, there are generally less risks associated with these interventions and they should always exist considered first. Non-pharmacological interventions should be tailored to the individual patient and the target behaviour(southward) and the impact carefully monitored.

Identify target behaviours

There are a diversity of challenging behaviours and symptoms that may present in older people with dementia. As different behaviours are oft best managed using different approaches, it is critical to first decide which behaviours are being targeted for management. Identifying target behaviours also allows the response to treatment to be more accurately monitored.^two

Mutual target problems and behaviours observed in elderly people with dementia or other mental illnesses include:²

Calling out
Assailment
Agitation
Hallucinations and illusions
Delusions
Wandering
Depression
Elevated mood
"Sundowning", e.1000. increased agitation in the tardily afternoon
Insomnia
Apathy/lack of motivation
Extreme anxiety
Resistance or unease towards carers
Intrusive behaviours
Inappropriate sexualised behaviour
Inappropriate urination or defaecation
Other inappropriate social behaviours

Record the target problem(south) and the response to treatment in the patient's notes.

Assess underlying causes and contributing factors

Medical and environmental factors can often precipitate or exacerbate BPSD. Patients presenting with BPSD should be assessed to exclude reversible causes, minimise precipitating factors, and to develop an individualised programme.

Cess should include consideration of the post-obit factors:^three

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 in that location a possibility of undetected pain, infection, constipation or discomfort?
Are at that place any factors in the patient's living environs, i.e. their dwelling house/care facility, or unmet personal needs which may be exacerbating behaviours?

Differential diagnosis: The 3Ds

Depression and delirium can also be associated with BPSD-like symptoms, therefore information technology is important to distinguish dementia from these conditions (referred to as the 3Ds). Differential features of the 3Ds are presented in Table one, merely there is considerable overlap and the 3Ds often co-exist. Severe depression tin present every bit a dementia-like illness (pseudodementia). Delirium can be acquired by infections, drug toxicity, booze withdrawal and metabolic disturbances.

Medicines that could precipitate or worsen BPSD

If an older person presents with new or worsening BPSD, current medicines should be excluded as a possible precipitant.

Medicines which tin exist associated with cognitive impairment include:⁵

Anticholinergics, east.yard. amitriptyline, oxybutynin
Anticonvulsants, eastward.g. carbamazepine, phenytoin
Lithium
Systemic corticosteroids, especially loftier doses
H2 antagonists, e.g. ranitidine
Some antibiotics, e.g. ciprofloxacin, norfloxacin, metronidazole, clarithromycin
Analgesics, particularly opioids
Anti-Parkinson's medicines
ACE inhibitors
Digoxin

Undetected medical weather

The post-obit medical weather condition tin can potentially cause, contribute to or mimic BPSD and should be considered:ⁱⁱⁱ

Pain
Infection (especially urinary tract infection)
Aridity or hyponatraemia
Constipation
Urinary retention
Anxiety
Fatigue
Hearing/visual impairment
Poor dental health

Personal or environmental factors that tin cause or exacerbate BPSD

Problems in the design and configuration of the patient's home or residential facility can cause or exacerbate restlessness, frustration, feet and disorientation. Unproblematic changes in the environment can be beneficial and may be worth discussing with the patient's family, carer or residential intendance director, including:^{three, eight}

Promote a at-home, tranquil surround, i.due east. avoid overstimulation
Ensure that the patient's home/room is at a comfortable temperature
Ensure easy access to the toilet
Take well lit environs
Use signs and memory aids for objects within the home that the patient commonly uses
Amend time orientation, e.g. prominent agenda/clock
If the patient is in a residential care facility, brand their environment as "dwelling-like" and reassuring every bit possible, by ensuring the patient is surrounded by their personal property, including culturally significant items
Encourage interest in group activities to foreclose boredom and loneliness
If possible, ensure consistency of carers
Ensure the patient has privacy

Encouraging people with dementia to participate in activities which are meaningful and enjoyable to them may better their sense of wellbeing and communication and pb to reductions in BPSD. This might include exercising, gardening, music, dancing, art or interactions with a pet. In that location is some express prove that aromatherapy tin can better symptoms of BPSD and increment quality of life in people with dementia.⁹

Behaviour management

Behaviour direction is defined as a structured intervention, ordinarily carried out by family or other caregivers, nether the supervision of a professional with expertise in this area. This might involve providing reinforcement for increased social activity or removing reinforcement for attention seeking behaviour. Behavioural management involving scheduling enjoyable events or engagement in problem-solving activities has been shown to improve symptoms of depression in people with dementia.¹⁰

Inappropriate sexual behaviour tin can be peculiarly challenging to address. Strategies include separating the patient from a person who might be a trigger for the behaviour and distraction with other activities, e.g. craft work to occupy the hands.¹¹

Tabular array 1: Differential features of the 3Ds: delirium, dementia and depression^four

Feature	Delirium	Dementia	Depression
Onset	Hours to days Usually sudden, ofttimes in the evening	Months to years Chronic and by and large insidious	Weeks to months Sometimes relatively abrupt and congruent with life changes, but may also be insidious and not clearly linked to life events
Elapsing	Hours to less than one month, rarely longer	Months to years	Months
Progression	Abrupt, fluctuating	Irksome but generally steady	Variable and uneven
Thinking	Disorganised, slow, incoherent	Paucity of thought, poor judgment; words difficult to observe	Intact with themes of helplessness, generally negative
Memory	Impaired, sudden	Impaired	Selective or patchy
Sleep	Nocturnal confusion	Ofttimes disturbed; nocturnal wandering	Reduced sleep with early morning wakening, or may oversleep
Awareness	Reduced	Articulate	Articulate
Alertness	Fluctuates; lethargic or hypervigilant	More often than not normal	Normal
Attention	Dumb, fluctuates	By and large normal	Minimal impairment but easily distracted

Antipsychotics are second-line

Antipsychotics may be considered for treating aggression, agitation or psychotic symptoms. They are not useful for wandering, shouting, touching or social withdrawal.

Antipsychotics are just appropriate for patients with BPSD if aggression, agitation or psychotic symptoms are causing severe distress or an immediate take a chance of harm to the patient or others.^{8, x} Unless emergency handling is required, not-pharmacological treatment should always be tried get-go and continued concurrently with antipsychotics.

Antipsychotics are not recommended for patients with balmy to moderate BPSD,¹⁰ and are not usually effective for other symptoms such as wandering, social withdrawal, shouting, pacing, touching or incontinence.¹² Antipsychotics do not appear to improve overall functioning, care needs or quality of life in patients with dementia.¹³

If an antipsychotic is prescribed, it should be given on a trial footing, and response and adverse effects regularly reviewed. An appropriate trial of an antipsychotic for patients with aggression or agitation is up to 4 weeks and upwards to three months for patients with psychotic symptoms, e.g. delusions or hallucinations.² If possible, antipsychotics should non exist used long-term for patients with dementia.

Antipsychotics can modestly improve BPSD in some patients

Antipsychotics are only modestly effective in managing BPSD, and the level of effectiveness varies between patients. They should not be regarded as a "cure" for BPSD. Traditionally, older antipsychotics (referred to as typical antipsychotics) such every bit haloperidol were used to manage symptoms in patients with dementia. Newer, atypical antipsychotics, such as risperidone, olanzapine, quetiapine and aripiprazole are now used. They are no more constructive than typical antipsychotics for BPSD, but are regarded as being better tolerated and safer (in terms of adverse furnishings) to utilise in older people.²

A meta-analysis which measured improvement in psychosis (e.g. delusions and hallucinations) and agitation (e.one thousand. assailment, excitability, oppositional behaviours or excessive motor activity) with use of atypical antipsychotics establish that the overall appreciable change was a 35% comeback in behaviour compared to baseline.^xiv A 30% improvement in behaviour is regarded every bit the minimum clinically observable change.¹⁴ Risperidone, olanzapine and aripriprazole had a minor, just statistically significant, beneficial effect on symptoms. The outcome of quetiapine was not significant.¹⁴ In contrast, a 2011 meta-analysis found that patients using quetiapine had a statistically significant improvement in BPSD, but the improvement was of questionable clinical significance.^xv

Which antipsychotic to cull for BPSD?

The pick of antipsychotic is based on their relative efficacy and adverse effects, along with subsidy status. Mutual adverse effects associated with all antipsychotics include sedation, dizziness, postural hypotension and defoliation, which may increase the risk of falls in older people.^{5, 16} The anticholinergic backdrop of antipsychotics tin can worsen cognition or cause delirium. Extrapyramidal adverse furnishings occur more than commonly with typical antipsychotics, merely can occur with risperidone even at relatively depression doses. Rarely, tardive dyskinesia can occur. Metabolic changes, e.g. significant weight gain, hyperglycaemia and furnishings of increased prolactin (e.yard. galactorrhoea), have too been associated with antipsychotics, but this is not observed to occur as oftentimes in older people. Many of these furnishings can be potentiated past interactions with other medicines and co-morbid weather condition.^xvi

Risperidone is the most extensively studied antipsychotic for use in BPSD, and is the only atypical antipsychotic approved for this use in New Zealand. Risperidone is, therefore, the first-line choice when an antipsychotic is prescribed for BPSD.¹⁴

If risperidone is not tolerated or non appropriate, then other antipsychotics may be considered in some patients. Other singular antipsychotics are not approved for apply in BPSD in New Zealand, and then are regarded equally being used "off-label" for this indication. Table 2 shows a comparison of agin furnishings for antipsychotics usually used in the treatment of BPSD.

For further information about off-label prescribing, including prescriber obligations, come across: "Unapproved medicines and unapproved employ of medicines: keeping prescribers and patients condom", BPJ 51 (Mar, 2013).

Quetiapine appears to be increasingly used in older people, and evidence from cohort studies suggests it is safer than other antipsychotics (including risperidone) in terms of mortality risk, but it may not be as effective.^{14, fifteen} Quetiapine at low doses (< 100 mg/day) is generally well tolerated in older people.

Olanzapine has been shown to be modestly effective for treating agitation, yet, the evidence is non as robust as information technology is for risperidone.¹⁸ Olanzapine is associated with more metabolic adverse effects, including rapid and meaning weight gain, dyslipidaemia and type 2 diabetes, than other antipsychotics.^{xiv, 16}

Aripiprazole has been shown to be modestly effective for symptoms of agitation and psychoses associated with BPSD.¹⁸ However, it is not subsidised for this use as a Special Authority is required for subsidised prescription and the criteria practice not cover BPSD. If aripiprazole is being considered, this should exist discussed with a Psychiatrist or Geriatrician.

Haloperidol has traditionally been used for BPSD and does not differ significantly in effectiveness from singular antipsychotics. Notwithstanding, it should mostly be avoided in older people given the high risk of extrapyramidal agin effects and increased bloodshed compared to atypical antipsychotics.^{2, xvi} Low-dose haloperidol has a restricted place in the short-term management of the acute symptoms of delirium (except in people with Parkinsonism of whatever cause).

The newer antipsychotics amisulpride, paliperidone (non subsidised) and ziprasidone (not subsidised for this indication) practise not nonetheless have an prove base to back up their utilize in BPSD.

Table two: Comparative risk of adverse effects of antipsychotics usually used for BPSD.^{xvi, xix}

	Risperidone	Quetiapine	Olanzapine	Aripiprazole	Haloperidol
Anticholinergic furnishings	+	+	+	•	+
Dyslipidaemia	++	++	+++	•	+
Extrapyramidal symptoms	++	•	+	+	+++
Hyperprolactinaemia	+++	+	+	•	+++
Neuroleptic cancerous syndrome	+	+	+	+	++
Postural hypotension	++	++	+	+	+
Prolonged QT interval	+	+	+	+	++
Sedation	+	++	++	+	+++
Seizures	+	+	+	+	+
Sexual dysfunction	+	+	+	+	+++
Type ii diabetes	+	+	++	+	+
Weight gain	++	++	+++	•	++
• = rare, + = lower risk, ++ = medium adventure, +++ = higher run a risk

Lewy Body dementia and dementia associated with Parkinson's disease

Approximately 10% of people with dementia have Parkinson's affliction or pregnant Parkinsonian symptoms.²⁰ Some of these people have Lewy Body dementia. Cadre symptoms of Lewy Body dementia include complex visual hallucinations, fluctuating cerebral impairment and Parkinsonism that is neither stroke nor drug-induced. It is recommended that a Psychiatrist or Geriatrician is consulted before considering prescribing any medicines for BPSD in people with Lewy Body dementia.

Typical antipsychotics such equally haloperidol should not be used in people with Lewy Torso dementia or dementia associated with Parkinson's disease as they can crusade dangerous extrapyramidal symptoms. At that place is also an increased risk of neuroleptic malignant syndrome, which is a life-threatening disorder induced past dopamine antagonists, characterised by hyperthermia, hypertonia ("lead pipe" rigidity in all muscle groups), changes in mental state, hyporeflexia and haemodynamic instability.²¹ Atypical antipsychotics, especially olanzapine, are as well best avoided, as they tin result in severe sensitivity reactions (e.g. marked extrapyramidal effects, defoliation, autonomic instability, falls and increased bloodshed).²⁰ Quetiapine may be used at low doses with extreme caution, in consultation with a Geriatrician or Psychiatrist, if cholinesterase inhibitors and non-pharmacological treatments have failed.²²

Safety concerns with antipsychotics in older people

Antipsychotics are associated with additional serious safety concerns when used in older people with dementia, such as an increased take a chance of stroke and overall mortality. When because antipsychotic handling, these risks need to be balanced confronting the gamble of injury (due to BPSD) for individual patients.

Increased chance of cerebrovascular events

Atypical antipsychotics, such every bit risperidone and olanzapine, have been associated with an increased risk of cerebrovascular adverse events, such every bit stroke, in older people with dementia, peculiarly those with more than avant-garde dementia. Information technology is not known what the exact mechanism for this clan is. There is evidence to propose that the risk of stroke may exist greatest in the first weeks of utilize of an singular antipsychotic, and people with a past history of cerebrovascular events are particularly at take chances.²³ The gamble of stroke may not render to baseline until half-dozen months afterward a patient ceases antipsychotic handling (depending on the length of treatment).²⁴ Typical antipsychotics are also associated with an increased run a risk of stroke, but there is some show that this take a chance is less than that with atypical antipsychotics.²⁴ Antipsychotics should be prescribed with caution in elderly people with dementia who have an increased cardiovascular hazard or personal or family unit history of cerebrovascular events.

An analysis of trials constitute an increased odds ratio of 2.thirteen for cerebrovascular adverse events in people taking antipsychotics for dementia. This take chances was especially high with risperidone (odds ratio 3.43).²⁵ Another systematic review and meta-assay too found that risperidone was associated with an increased adventure of stroke (odds ratio 3.12).¹⁴ The number needed to damage was 53.^fourteen A comparative written report institute that in that location was no difference in risk of stroke betwixt patients taking risperidone and patients taking olanzapine, i.e. suggesting that olanzapine has the same increased risk.¹⁷ Patients taking quetiapine had a smaller risk of cerebrovascular agin events than those taking olanzapine.¹⁷

Increased bloodshed

Singular antipsychotics have been associated with an increased overall mortality charge per unit in older people with dementia. In 2005, the Us Nutrient and Drug Administration (FDA) stated that the adventure of mortality was increased one.vi -1.7 - fold in patients treated with atypical antipsychotics for BPSD.²⁶ A subsequent meta-analysis besides plant a like mortality rate with atypical antipsychotics.⁴ For every 87 patients treated with an antipsychotic for dementia, one patient will die.¹⁴

The hazard of death is significantly lower for quetiapine compared to risperidone or olanzapine, which in turn has a lower risk of expiry than haloperidol.^{27, 28} The highest increase in bloodshed is in the first four months of treatment and in the first thirty days for haloperidol, although report participants receiving haloperidol may have been more unwell, and had received the medicine during an inpatient infirmary access.²⁷ This finding contrasts to that of the DART-AD study which found that the risk of death may increase with long-term treatment.²⁹

The nigh common atmospheric condition associated with cause of death appear to be pneumonia or cardiac failure or arrest.³⁰ Antipsychotics prolong the QT interval, which can issue in ventricular tachyarrhythmia and sudden cardiac death. The adventure of cardiac death increases with increasing dose, and the risk is similar between typical and atypical antipsychotics.³¹ The risk is no longer elevated when employ of antipsychotics ceases.³¹ Antipsychotics should be prescribed with caution in patients taking other medicines which prolong the QT interval, e.thou. erythromycin, citalopram, venlafaxine.

A total listing of medicines with the potential to cause prolonged QT interval is available from: world wide web.qtdrugs.org

Potential increased run a risk of pneumonia

Population based studies have suggested that there is an increased gamble of pneumonia in older people (with or without dementia) treated with antipsychotics. The risk is thought to be greater with atypical antipsychotics, and the take a chance may be highest during the get-go calendar week of treatment.³²

Information technology is not known how antipsychotics increment the take a chance of pneumonia, however, dysphagia (due to H1 receptor blockade), dry out mouth (due to the anticholinergic issue), sedation (facilitating aspiration pneumonia) and directly or indirect furnishings on the immune organization have been suggested equally possible mechanisms.³²

Guidance for prescribing antipsychotics in elderly people

Obtain informed consent

Before prescribing an antipsychotic for BPSD, a total word should take place regarding the possible benefits and risks of treatment, including the increased risk of stroke and all-cause mortality in people with dementia.^{2, ten} Many patients with dementia will lack competency to determine on their own handling, therefore the person legally responsible for the patient'south medical decisions must be given information that is easily understood so they can make an informed decision.²

"Start low and go tedious"

If a trial of antipsychotic treatment is considered necessary, the starting dose should be as depression equally possible (Table iii). The starting dose can exist divided or timed according to the behaviour, e.yard. a lunchtime dose for patients exhibiting increased agitation towards the end of the 24-hour interval ("sundowning").

The dose tin can exist slowly increased at no less than weekly intervals, depending on response. High doses should be avoided, and treatment should be stopped if it has not significantly improved the target behaviour.^two

Table 3: Recommended starting and maintenance doses for antipsychotics in older people^{two, 5}

Medicine	Dose	Comments
Risperidone	0.25 – 0.5 mg initially, titrated to maximum 2 mg daily in patients with dementia (half dozen mg daily may exist tolerated in other patients), in i or two divided doses	Merely approved atypical antipsychotic for BPSD. At higher doses it may behave more than like a typical antipsychotic in terms of a higher incidence of extrapyramidal furnishings.
Quetiapine	12.5 mg initially, titrated to maximum 100 mg daily in patients with dementia (300 mg daily may be tolerated in other patients), in two or more than divided doses	Electric current evidence suggests limited effectiveness for BPSD, although possibly safer in terms of bloodshed risk
Olanzapine	2.five mg initially, titrated to maximum 10 mg daily (less in patients with dementia), in one or 2 divided doses	May be modestly effective for treating agitation, but generally not recommended in people with dementia. Associated with greater comparative risk of agin metabolic effects.
Aripiprazole	5 mg – 10 mg daily	Not subsidised for apply in BPSD
Haloperidol	0.25 mg, twice daily, titrated up to iii mg daily	Effective for the curt-term direction of the acute symptoms of delirium (except in people with Parkinsonism of whatsoever crusade). Not recommended for long-term use. High risk of extrapyramidal agin effects and increased bloodshed compared to atypical antipsychotics.

Monitor closely for agin furnishings

Older people are especially vulnerable to the agin effects of antipsychotics, and these may outweigh any benefits. Adverse effects are generally dose-related and tin be minimised past keeping the dose as depression as possible.

Monitor for:

CNS depression – sedation, increased confusion or cognitive impairment. Concurrent medicines may worsen effects, including benzodiazepines, opioids, antihistamines, antidepressants, anti-Parkinson's medicines.
Anticholinergic furnishings – dry mouth, constipation, urinary retention, blurred vision, delirium. Concurrent medicines may worsen effects, including tricyclic antidepressants, oxybutynin and opioid analgesics.
Dizziness and postural hypotension – increases risk of falls. Concurrent medicines may worsen furnishings, including antihypertensives, diuretics, SSRIs (causing hyponatraemia).
Extrapyramidal effects – dyskinesias, dystonias
Metabolic changes – monitor weight and monitor HbA_1c at baseline, then every three months in year i (or fasting glucose monthly for starting time three months in patients at loftier risk)*, and annually for subsequent years
Infection – in detail urinary tract infections and pneumonia

*HbA_1c should be used in preference to a fasting glucose test for investigating for diabetes in nearly clinical situations. Yet, HbA_1c is non reliable when blood glucose levels ascent too rapidly to affect HbA_1c such as in some patients newly initiated on atypical antipsychotics. Therefore, in patients with other hazard factors for diabetes, fasting blood glucose is recommended at baseline, and monthly for the first iii months. HbA_1c tin exist used for long-term monitoring.

Regularly review the need for standing handling

Gradual dose reduction and eventual withdrawal should exist tried every three months. There have been very few studies done to measure the effectiveness of antipsychotics for BPSD longer than three months. In add-on, BPSD may exist temporary. A recent Cochrane review concluded that antipsychotics could exist routinely withdrawn without adversely affecting behaviour, in all patients apart from those with severe symptoms.³³

Longer-term utilise of antipsychotics is reported to be associated with a higher hazard of relapse of symptoms. A study plant that in patients who had been treated with risperidone for BPSD for four to eight months, discontinuation was associated with an increased hazard of relapse.³⁴ The risk of recurrence of symptoms may besides be higher in people with previously severe symptoms and if discontinuation has caused recurrence earlier.

Withdrawal of antipsychotics should be done gradually, e.thousand. by reducing the dose past l% every ii weeks then stopping after two weeks on the minimum dose. Withdrawal may be slower if the antipsychotic has been prescribed for a longer period of time. Monitor for recurrence of target behaviours or the emergence of new symptoms.

Challenging behaviours or symptoms tin persist over fourth dimension and in certain circumstances it may be justifiable to continue antipsychotics. Reasons for standing antipsychotics include:²

A high risk of adverse consequences if medicines are withdrawn, peculiarly if treatment has only been partially effective or prior relapses accept occurred
When the consequences of symptom relapse are deemed to be unacceptably astringent
When no alternative treatment approaches have been possible or effective in the past

Alternatives to antipsychotics may too be considered; word with a Geriatrician or Psychiatrist is recommended. There is a small body of prove to support the apply of SSRIs, such as citalopram and sertraline, for agitation and psychosis in people with dementia, with no statistically significant differences found betwixt the effectiveness of SSRIs and antipsychotics.³⁵ There is some limited emerging show that levetiracetam may be useful for the behavioural symptoms of dementia.³⁶