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盧盈辰2015/5/20

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Management of neuropsychiatric symptoms of dementia

+Outline

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• Dementia

• Introduction

• Evaluation

• Mild to moderate agitation

• Severe aggression or psychosis

• Depression

• Sleep disorders

• Support for caregivers

• Conclusion

+Dementia

Dementia is a disorder that is characterized by a decline in cognition involving one or more cognitive domains.

Learning and memory, language, executive function, complex attention, perceptual- motor, social cognition.

Dementia syndromes

Alzheimer’s disease (AD) (60%-80%)

Dementia with Lewy bodies (DLB)

Frontotemporal dementia (FTD)

Vascular (multi-infarct) dementia (VaD)

Parkinson disease with dementia (PDD)

DSM-IV/DSM-V (DSM=Diagnostic and Statistical Manual of Mental Disorders)

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+Dementia

In the United States in 2011, there were an estimated 4.5 million individuals over the age of 65 years living with clinical AD.

0.7 million people age 65 to 74 years

2.3 million age 75 to 84 years

1.8 million 85 years and older

This figure is projected to rise to 13.8 million in the United States and >100 million worldwide by 2050.

The age-standardized prevalence of dementia ranges from 5 to 7 percent in most countries except for Sub-Saharan Africa and Asia, where rates are lower.

依據衛生福利部委託台灣失智症協會進行2011至2012年底的全國失智症盛行率調查結果顯

示,台灣老年失智症盛行率約 5%。

台灣失智總人口在2011年時估算就已超過19 萬人,其中失智症老人 (65 歲以上) 超過 17 萬人, 預估到2056年失智人口將達72萬人。

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內科學誌 2014; 25: 151-7

+Dementia

Cardinal symptoms

Memory impairment

Language dysfunction

Impaired visuospatial skills

Executive function and judgement

Changes in personality or behavior

Apraxia

Olfactory dysfunction

Seizures

Motor signs

Neuropsychiatric symptoms

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+Introduction

Almost all people diagnosed with AD develop neuropsychiatric symptoms at some stage during their disease.

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Table 1. Neuropsychiatric symptoms of dementiaDelusions ApathyHallucinations IrritabilityDepression DisinhibitionAnxiety Wandering or pacingEuphoria Sleep disturbancesAggression

One or more symptoms are observed in 61-92% of patients with dementia.

+Introduction

Sophisticated neuroimaging techniques are increasingly able to define neuroanatomical substrates for some of these behaviors.

The right hemisphere and right frontal lobe appear important in the mediation of social and emotional behaviors.

Evaluation

Screening for neuropsychiatric symptoms in patients with dementia should be done at regular follow-up visits.

Assessing the associated caregiver distress is also important in determining the urgency of intervention.

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+Evaluation

Agitation and other behavioral abnormalities can arise from a variety of underlying causes in patients with dementia.

Agitation is driven by pain, fear, confusion, or poor sleep.

Behavioral changes herald a new infection or medication toxicity

Identifying the genesis of the abnormal behavior is critical to effective management.

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+Evaluation

Table 2-1. Common causes of delirium and confusional states Drugs and toxins Metabolic derangementsPrescription and non-prescription medications

Electrolyte disturbance

Drugs of abuse Endocrine disturbanceWithdrawal states Hypercarbia Medication side effects Hyperglycemia and hypoglycemiaPoisons Hyperosmolar and hypoosmolar statesInfections Hypoxemia Sepsis Inborn errors of metabolismSystemic infections; fever-related delirium Nutritional

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+Evaluation

Table 2-2. Common causes of delirium and confusional states Brain disorders Systemic organ failure Physical disorders

CNS infections Cardiac failure Burns Epileptic seizures Hematologic Electrocution Head injury Liver failure Hyperthermia Hypertensive encephalopathy

Pulmonary disease Hypothermia

Psychiatric disorders Renal failure Trauma

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Especially non-convulsive status epilepticus

These possibilities should be ruled out prior to initiation of any treatment.

+Evaluation

Other precipitating factors--

Confusion or misunderstanding due to cognitive, language, or memory deficits.

If aggression appears to emerge in moments of confusion, behavioral management is usually sufficient after analysis of the antecedent behaviors.

Frightening, paranoid delusions

If delusions appear to trigger aggression, pharmacologic treatment may be helpful or necessary.

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+Evaluation

Other precipitating factors--

Pain or discomfort

Adults with mild to moderate dementia can report pain reliably; for patients with advanced dementia, clinicians must rely on caregivers.

Depression

Agitation or aggression may be the primary manifestation of depression in a patient too impaired to express distress in any other manner.

Sleep disorders

Disturbed sleep is common in patients with dementia and itself can be caused by a variety of factors.

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+Evaluation

Pain assessment

Facial expressions

Verbalizations/vocalizations

Body movements

Changes in interpersonal interactions

Changes in activity patterns/routines

Mental status changes

PAINAD-Pain Assessment in Advanced Dementia

Breathing independent of vocalization, negative vocalization, facial expression, body language and consolability.

Total scores ranges from 0 to 10, with a higher score indicating more severe pain.

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Evaluation

http://www.nursingconnect.tw/

Table 3. PAINAD晚期失智症疼痛評估量表

指標 0分 1分 2分 得分

呼吸 正常呼吸 偶爾費力呼吸短暫的過度換氣

持續費力呼吸且呼吸音吵雜；

長時間過度換氣；陳施式呼吸

負向發聲 無 偶爾嗚咽/呻吟以負向或不雅的言語說話

反覆不安地大聲喊叫大聲嗚咽或呻吟哭泣

面部表情 微笑或無表情 傷心、害怕、皺眉 臉部表情痛苦

肢體語言 放鬆 緊張、痛苦、踱步、坐立不安 僵硬、雙拳握緊；膝蓋上屈；

揮拳；把人拉開或推開

可安撫性 不需安撫 聲音或碰觸可使其分散注意力 無法被安撫、分散注意力，或

使其放心

總分

+Mild to moderate agitation

A proactive approach, with early recognition and treatment of mild symptoms

With collaboration between health care providers, patients, caregivers, and community agencies.

Provide maximal benefits in managing these troublesome symptoms.

Non-pharmacologic therapies

May be effective in reducing agitation and anxiety in patients with dementia.

Aromatherapy, exercise training, music therapy, pet therapy, massage and touch therapy.

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+Mild to moderate agitation

Anti-dementia drugs

A cholinesterase inhibitor are well tolerated and may have additional benefit for cognition and function.

The potential efficacy of memantine requires further study.

Pain management

Prescribe a trial of scheduled analgesics.

Use a stepped-care approach to analgesic prescribing.

Start low, go slowly, but use enough.

Monitor the patient carefully to balance risks and benefits of pain treatment versus persistent pain.

Adequate pain control may be observed as improvements in behavior and function.

Reducing neuropsychiatric symptoms and lower agitation scores.

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+Mild to moderate agitation

Drugs with uncertain benefit--

Antiepileptic drugs have been investigated for the treatment of neuropsychiatric symptoms in dementia because of their mood stabilizing properties:

Carbamazepine

Valproate

Gabapentin

Lamotrigine

Melatonin and/or light therapy

Low doses of methylphenidate are often helpful for apathy but can precipitate agitation; careful monitoring is therefore required.

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+Mild to moderate agitation

Drugs to avoid--

Benzodiazepine side effects include worsening gait, potential paradoxical agitation, and possible physical dependence.

Limited to brief stressful episodes.

Shorter half-lives should be preferred.

Antihistamines are widely used for mild sleep disturbances but are discouraged

High rates of side effects, particularly for drugs with anticholinergic effects, such as diphenhydramine.

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+Severe aggression or psychosis

When non-pharmacologic interventions fail to manage symptoms effectively and they result in severe distress or safety issues, pharmacologic therapy may become necessary.

Selection of pharmacologic therapy should be symptom based.

Antipsychotic drugs-typical antipsychotics

Haloperidol, thioridazine, thiothixene, chlorpromazine, trifluoperazine and acetophenazine.

There was no clear evidence of benefit for these agents in patients with dementia.

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+Severe aggression or psychosis

Antipsychotic drugs-atypical neuroleptics have been the choice for treating hallucinations in patients with dementia.

These drugs may increase mortality, and not approved by FDA.

They should not be used routinely.

There is no good alternatives.

Their benefits often still outweigh their risks in patients with dementia when treatment of hallucinations and delusions is critical.

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+Severe aggression or psychosis

Antipsychotic drugs--

For patients who have neuropsychiatric symptoms, particularly psychosis, that are severe and debilitating and inform patients and families of the risks.

Somnolence is also concern and may be dose limiting.

Olanzapine: 2.5 mg QD-5 mg BID.

The incidence of EPS is low but metabolic side effects can be more severe.

Risperidone: 1 mg QD.

Higher doses are associated with drug-induced parkinsonism.

Quetiapine: 25 mg HS-75 mg BID.

An alternative.

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+Severe aggression or psychosis

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Table 4.

Applied therapeutics 10th chapter 82 p. 1932

+Severe aggression or psychosis

Serious adverse events--

Antipsychotic medications have been associated with an increased risk of stroke, myocardial infection, and death.

Higher doses are associated with increased risk.

All antipsychotic drugs should be considered a risk, although several studies have found that the risks are highest with haloperidol and lowest with quetiapine.

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+Severe aggression or psychosis

Antidepressants--

Citalopram (SSRIs) is useful in the management of agitation and paranoia in patients with AD. (10-20 mg daily)

A maximum daily dose of 20 mg for patients older than 60 years of age.

Should be avoided in patients at increased risk for arrhythmias.

Congenital long QT syndrome, hypokalemia, hypomagnesemia and active heart disease.

Withdrawing the medications should be made periodically.

Use of physical restraints.

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+Depression

Diagnosis

Depressive pseudo-dementia.

Elderly patients who become depressed are at increased risk of being demented or developing dementia.

Patients with dementia may develop apathy, sleep impairment, and social withdrawal.

Patients with dementia may become depressed in reaction to slipping mental capacity or as a direct biological consequence of the the underlying neurologic disorder.

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Elderly patients

Men > Women

+Depression

Table 5. Depression in Alzheimer-type dementia

A. 3 or more of the following symptoms, present during the same two-week period, and representing a change from a previous level of functioning. Either item-one or item-two must be include:

1. Clinically significant depressed mood 6. Psychomotor retardation or agitation

2. Decreased positive affect or pleasure in response to social contacts and usual activities

7. irritability

3. Social isolation or withdrawal 8. Fatigue or less of energy

4. Disturbed appetite 9. Feeling of worthlessness, hopelessness, or inappropriate guilt

5. Disturbed sleep 10. Recurrent thoughts of death or suicidal ideation, plan, or any attempt

B. Meets criteria for Alzheimer-type dementia

C. Depressive symptoms cause clinically significant distress or disruption in function

D. Symptoms do not occur exclusively during an episode of delirium

E. Symptoms are not due to a direct physiological effect from a substance (medication or drug of abuse)

F. Symptoms are not better accounted for by another condition

Specify if: Specify if:

Co-occuring onset: onset antedates or co-occurs with AD symptoms

With psychosis of AD

Post-AD onset: onset occurs after AD diagnosis With other significant behaviorial signs or symptoms

With past history of mood disorder

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+Depression

Management--

Tricyclic antidepressants (TCA)

Amitriptyline

Nortriptyline

Serotonin reuptake inhibitors (SSRIs)-side effect profile, drug interactions, and cost.

Fluoxetine

Paroxetine

Citalopram 20 mg daily in elderly patients

Sertraline

Venlafaxine

Bupropion

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+Sleep disorders

Sleep disturbances are affecting an estimated 25-35% of AD patients.

Causes can include contributions from

Depression and anxiety

A decrease in daytime physical activity

Nocturia

Effects of medications

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+Sleep disorders

Non-pharmacologic treatment

An activity/exercise program

Avoidance of daytime naps

Limiting evening beverages, elimination of evening alcohol and coffee

Delaying bedtime

Pharmacotherapy

Trazodone

Combined light treatment and melatonin

Benzodiazepines

Antihistamine

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+Support for caregivers

Caregivers of patients with dementia can suffer significant stress, particularly as cognitive function declines or behavioral symptoms worsen.

Counseling and support interventions benefit caregivers in the short term as measured by a reduction in stress and improvement in emotional wellbeing and quality of life.

Optimizing caregiver support might also help to keep patients with dementia cared for in home.

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+Conclusion

The first step is to identify precipitating factors and rule out and treat a medical cause or superimposed delirium.

Environmental, behavioral, and other non-pharmacological therapies can be effective in this population.

When appropriate, are preferred over medications.

Cholinesterase inhibitors do not produce clinically significant improvement in neuropsychiatric symptoms, but modest improvement in cognition.

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+Conclusion

The use of low doses of olanzapine or risperidone in patients with severe, disabling symptoms after informing families of the mortality risk.

SSRIs is suggested for the treatment of depression in AD. Citalopram is often used and sertraline is a well studied alternative to citalopram.

Sleep disturbances are common in patients with dementia. Non- pharmacologic strategies are generally preferred to pharmacotherapy.

Small doses of melatonin or trazodone.

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Thanks for your attention

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