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1 BEHAVIORAL PROBLEMS IN DEMENTIA 2 OBJECTIVES • Know and understand: • Factors precipitating behavioral disturbances • How to rule out medical, environmental, and caregiving causes of behavioral problems • Environmental and non-pharmacologic management of behavioral disturbances • When and how to medicate 3 TO P I C S C O V E R E D • Clinical Features • Assessment and Differential Diagnosis • Basic Approach to Treatment • Treatments for Specific Disturbances 4 INTRODUCTION • As many as 80%–90% of patients with dementia develop at least one psychotic symptom or behavioral disturbance over the course of their illness • Behavioral disturbances or psychotic symptoms in dementia often precipitate nursing-home placement • Disturbances are potentially treatable, so it is vital to recognize them early 5 C L I N I C A L F E AT U R E S • Psychiatric symptoms may develop that resemble discrete mental disorders such as depression or mania • The course and features are more difficult to predict, and treatments are less reliably effective, than in younger adults without dementia • Neuropsychiatric symptoms such as apathy, poor self-care, or paranoia may be the first indication of dementia C L I N I C A L F E AT U R E S : A G I TAT I O N ( 1 o f 2 ) • Reflects loss of ability to modulate behavior in a socially acceptable way • May involve verbal outbursts, physical aggression, resistance to bathing or other care needs, and restless motor activity such as pacing or rocking • Often occurs concomitantly with psychotic symptoms such as paranoia, delusional thinking, or hallucinations 6 C L I N I C A L F E AT U R E S : A G I TAT I O N ( 2 o f 2 ) • Caregivers, both professional and family, may use the word agitation to describe a variety of behaviors and psychologic symptoms • The clinician must consider agitation to be a nonspecific complaint and pursue further history of the problem • Overt resistance to care is most often seen in later stages of dementia, but it may be a first sign of incipient cognitive decline 7 8 ASSESSMENT • Obtain a history from both the patient and an informant • Elicit a clear description of the behavior: Temporal onset and course Associated circumstances Relationship to key environmental factors, such as caregiver status and recent stressors DIFFERENTIAL DIAGNOSIS: MEDICAL CAUSES • Disturbances that are new, acute in onset, or evolving rapidly are most often due to a medical condition or medication toxicity • An isolated behavioral disturbance in a demented patient can be the sole presenting symptom of acute conditions such as pneumonia, UTI, arthritis, pain, angina, constipation, or uncontrolled diabetes • Medication toxicity can present as behavioral symptoms alone 9 DIFFERENTIAL DIAGNOSIS: E N V I R O N M E N TA L C A U S E S 10 • Life stressor (eg, death of a spouse or other family member) • Change to daylight savings time or travel across time zones • New routine, new caregivers, or new roommate • Overstimulation (eg, too much noise, crowded rooms, close contact with too many people) • Understimulation (eg, relative absence of people, spending much time alone, use of television as a companion) • Disruptive behavior of other patients 11 DIFFERENTIAL DIAGNOSIS: S T R E S S I N C A R E G I V I N G R E L AT I O N S H I P • May exacerbate/cause a behavioral disturbance • Relationships with potential for stress include: Inexperienced caregivers Domineering caregivers Caregivers who themselves are impaired by medical or psychiatric disturbances M A N I F E S TAT I O N O F D E M E N T I A : C ATA S T R O P H I C R E A C T I O N • Defined as an acute behavioral, physical, or verbal reaction to environmental stressors that results from inability to make routine adjustments in daily life • Might include anger, emotional lability, or aggression when confronted with a deficit • Best treated by identifying and avoiding precipitants, providing structured routines and activities, and recognizing early signs so the patient can be distracted and supported before reacting 12 M A N I F E S TAT I O N O F D E M E N T I A : B R A I N D E T E R I O R AT I O N • Persistent behavioral disturbances and those with more insidious onset are likely to relate to brain deterioration • Behavioral disturbances related to dementia fall into 3 groups, which may overlap: mood symptoms, psychosis, specific behaviors • If the disturbance is polysymptomatic, one approach is to target treatment to the prevailing feature: psychosis (delusions or hallucinations), mood symptoms (dysphoria, sadness, irritability, lability), aggression, or agitation 13 B E H AV I O R A L S Y M P TO M S BY DEMENTIA TYPE • Frontotemporal dementia (Pick’s disease): often associated with prominent disinhibition, compulsive behaviors, and social impairment In severe cases, a syndrome of hyperphagia, hyperactivity, and hypersexuality may occur • Dementia with Lewy bodies: prominent psychosis characterized by visual hallucinations • Behavioral problems can occur in all dementia types 14 15 T R E AT M E N T S F O R S P E C I F I C DISTURBANCES: GENERAL PRINCIPLES • Management of pain, dehydration, hunger, and thirst is paramount • Consider the possibility of positional discomforts or nausea secondary to medication effects • Modify environment to improve orientation • Good lighting, one-on-one attention, supportive care, and attention to personal needs and wants are also important B E H AV I O R A L I N T E RV E N T I O N S (1 of 3) • Treat underlying medical precipitants • Replace poorly fitting hearing aids, eyeglasses, and dentures • Remove offending medications, particularly anticholinergic agents • Keep the environment comfortable, calm, and homelike with use of familiar possessions • Provide regular daily activities and structure; refer patient to adult day care programs, if needed 16 B E H AV I O R A L I N T E RV E N T I O N S (2 of 3) • Monitor for new medical problems • Attend to patient’s sleep and eating patterns • Install safety measures to prevent accidents • Ensure that the caregiver has adequate respite • Educate caregivers about practical aspects of dementia care and about behavioral disturbances • Teach caregivers communication skills, how to avoid confrontation, techniques of ADL support, activities for dementia care 17 B E H AV I O R A L I N T E RV E N T I O N S (3 of 3) • Simplify bathing and dressing with the use of adaptive clothing and assistive devices, if needed • Offer toileting frequently and anticipate incontinence as dementia progresses • Provide access to experienced professionals and community resources • Refer family and patient to local Alzheimer’s Association • Consult with caregiving professionals, such as geriatric case managers 18 19 TO R E D U C E S U N D O W N I N G • Give adequate daytime stimulation • Maintain adequate levels of light in daytime • Establish bedtime routine and ritual • Remove environmental factors that might keep patient awake • Discourage drinking stimulants or smoking near bedtime • Give diuretics, laxatives early in day • Place familiar objects at bedside 20 T E A C H T H E TA D A A P P R O A C H • T: Tolerate-allow the patient to go with his flow and monitor. • A: Anticipate-tethering is going to be a problem: eliminate nursing and medical interventions ASAP • DA: Don’t agitate-Don’t ask or question or reorient-their world is the right one! T R E AT M E N T O F MOOD DISTURBANCES • Reduce aversive environmental stimuli • Assess physical health comprehensively • Try recreation programs and activity therapies • Consider antidepressants for: Depression of 2 weeks’ duration resulting in significant distress Depressive features lasting >2 months after initiation of behavioral interventions 21 S E L E C T I V E S E R O TO N I N R E U P TA K E I N H I B I TO R S ( 1 o f 2 ) Medication Daily Dose Uses Citalopram 10–20mg Depression, anxiety (offmax dose label) Escitalopram 5–20 mg Fluoxetine 10–40 mg Depression, anxiety Depression, anxiety Precautions GI upset, nausea, insomnia 22 S E L E C T I V E S E R O TO N I N R E U P TA K E I N H I B I TO R S ( 2 o f 2 ) Medication Paroxetine Sertraline Vilazodone Daily Dose Uses 10–40 mg Depression, anxiety 25-100 mg Precautions Inhibits cytochrome P-450 Depression, anxiety 10-40 mg Depression, anxiety 23 Take with food, dose adjust in severe hepatic disease S E R O TO N I N N O R E P I N E P H R I N E R E U P TA K E I N H I B I TO R S Medication Daily Dose Uses 24 Precautions Desvenlafaxine 25–50 mg Depression, fibromyalgia Nausea, hypertension, dry mouth, dizziness, headaches Duloxetine 20–60 mg Depression, diabetic neuropathy Nausea, dry mouth, dizziness Mirtazapine 7.5–30 mg Useful for depression with insomnia Sedation, hypotension Venlafaxine 25–150 mg Useful in severe depression Hypertension, insomnia TRICYCLIC ANTIDEPRESSANTS Medication Daily Dose Desipramine 10–100 mg Nortriptyline Uses Depression, anxiety 10–75 mg High efficacy for depression if side effects are tolerable; therapeutic level 50– 150 ng/dL Precautions Anticholinergic effects, hypotension, sedation, cardiac arrhythmias Anticholinergic effects, hypotension, sedation, cardiac arrhythmias 25 O T H E R D R U G S TO T R E AT D E P R E S S I V E F E AT U R E S Medication Daily Dose Uses Precautions Bupropion 75–225 mg More activating, lack of cardiac effects Irritability, insomnia Trazodone 25–150 mg When sedation is desirable Sedation, falls, hypotension 26 T R E AT M E N T O F M A N I C - L I K E B E H AV I O R • Symptoms resemble those of bipolar disorder (pressured speech, disinhibition, elevated mood, intrusiveness, hyperactivity, reduced sleep) • The important distinction in the dementia patient is the frequent co-occurrence with confusional states and a tendency to have fluctuating mood (ie, irritable or hostile as opposed to euphoric) 27 M O O D S TA B I L I Z E R S F O R M A N I C - L I K E B E H AV I O R ( 1 o f 3 ) 28 Drug Geriatric Dosage Adverse Effects Comments Carbamazepine 200–1000 mg/day (therapeutic level 4–12 μg/mL) Nausea, fatigue, ataxia, blurred vision, hyponatremia Poor tolerability in older adults; must monitor CBC, LFTs, electrolytes q 2 weeks for first 2 months, then q 3 months The 4 agents in this table are approved by the FDA for the treatment of bipolar disorder but are off-label for treatment of manic-like behavior associated with dementia. Note FDA warning for increase in suicidal thoughts/behaviors with anticonvulsant agents. M O O D S TA B I L I Z E R S F O R M A N I C - L I K E B E H AV I O R ( 2 o f 3 ) 29 Drug Geriatric Dosage Adverse Effects Comments Lithium 150–1000 mg/day (therapeutic level 0.5–0.8 mEq/L) Nausea, vomiting, tremor, confusion, leukocytosis Poor tolerability in older adults; toxicity at low serum levels; monitor thyroid and renal function Divalproex sodium 250–2000 mg/day (therapeutic level 40–100 μg/mL) Nausea, GI Requires monitoring of upset, ataxia, CBC, platelets, LFTs at sedation baseline and q 6 months; better tolerated than other mood stabilizers in older patients M O O D S TA B I L I Z E R S F O R M A N I C - L I K E B E H AV I O R ( 3 o f 3 ) 30 Drug Geriatric Dosage Adverse Effects Comments Lamotrigine 25–200 mg/day Sedation, skin rash, rare StevensJohnson syndrome, anemia, neutropenia Increased adverse events and interactions when used with divalproex, slow-dose titration required T R E AT M E N T O F D E L U S I O N S A N D H A L L U C I N AT I O N S • Delusions (paranoid or unfounded ideas) or hallucinations (false perceptions) typically require pharmacologic treatment if: – The patient is disturbed by these experiences – Symptoms lead to disruptions in the patient’s environment that cannot otherwise be controlled • Clinical criteria for the diagnosis of Alzheimer’s dementia with psychosis specifies the presence of delusions or hallucinations for at least 1 month, at least intermittently, that cause distress for the patient 31 32 ANTIPSYCHOTIC AGENTS (1 of 5) Drug Daily Dose Adverse Events Aripiprazole 5–15 mg Mild sedation, mild hypotension Tablet, liquid concentrate Asenapine 5-10 mg Sedation Only sublingual Clozapine 12.5– Sedation, 200 mg hypotension, anticholinergic effects, agranulocytosis Comments Weekly CBC required; poorly tolerated by older adults; reserve for treatment of refractory cases Forms Tablet, rapidly dissolving tablet 33 ANTIPSYCHOTIC AGENTS (2 of 5) Drug Daily Dose Adverse Effects Haldol 0.5 – 3 Sedation, mg extrapyramidal symptoms Comments 1st generation agent Iloperidone 1-12 mg Sedation, Dose reduce with orthostatic CYP3A4 & hypotension CYP2D6 inhibitors Lurasidone 40-80 mg Sedation Do not exceed 40mg daily with CYP3A4 inhibitors Forms Tablet, liquid, IM, long-acting 34 ANTIPSYCHOTIC AGENTS (3 of 5) Drug Olanzapine Daily Dose Adverse Effects 2.5–10 Sedation, mg falls, gait disturbance EPS, sedation Comments Forms Weight gain Tablet, rapidly dissolving tablet, IM injection 1st generation agent Tablet Perphenazine 2 -12 mg Paliperidone 1.5 – Sedation, 12 mg fatigue, GI upset, EPS Dose reduce in Sustained renal impairment release, depot IM Quetiapine 25-200 Sedation, hypotension Ophthalmologic Sustained exam every 6 mo release tablet 35 ANTIPSYCHOTIC AGENTS (4 of 5) Drug Daily Dose Risperidone 0.5–2 mg Ziprasidone 40– 160 mg Adverse Effects Sedation, hypotension, EPS with doses > 1 mg/day Higher risk of prolonged QTc interval, hyperglycemia Comments Forms Tablet, rapidly dissolving tablet, liquid concentrate, depot IM injection Little published Capsule, IM information on injection use in older adults. Warning about increased QTc prolongation 36 A N T I P S Y C H OT I C A G E N T S ( 5 o f 5 ) • All of these medications have warnings about hyperglycemia, cerebrovascular events and increase in all-cause mortality in patients with dementia • All of these medications are off-label for treatment of psychosis in dementia 37 C H O L I N E S T E R A S E I N H I B I TO R S • In patients with mild to moderate Alzheimer’s disease, donepezil or galantamine are better than placebo in reducing psychosis and behavioral disturbances • In patients with dementia with Lewy bodies, who are sensitive to the EPS of antipsychotic agents, cholinesterase inhibitors have been reported to reduce visual hallucinations 38 MANAGING SLEEP DISTURBANCES • Improve sleep hygiene (see next slides) • Use bright-light therapy • Treat associated depression, delusions • If the above do not succeed, consider (off-label): Trazodone 25–150 mg at bedtime Mirtazapine 7.5–15 mg at bedtime Zolpidem 5 mg at bedtime • Avoid benzodiazepines or antihistamines 39 SLEEP HYGIENE (1 of 2) • Establish a stable routine for going to bed and awakening • Pay attention to noise, light, and temperature • Increase daytime activity and light exercise • Reduce or eliminate caffeine, nicotine, alcohol • Reduce evening fluid consumption to minimize nocturia 40 SLEEP HYGIENE (2 of 2) • Give activating medications early in the day if patient unable to eliminate • Control nighttime pain • Limit daytime napping to brief periods of 20 to 30 minutes • Use relaxation, stress management, and breathing techniques to promote natural sleep MANAGING AGGRESSION A N D A G I TAT I O N • Behavioral interventions: distraction, supervision, routine, structure, caregiver education and support, music and physical therapy, or aromatherapy • Behavior modification using positive reinforcement of desirable behavior • Avoid physical restraints 41 42 MANAGING HYPERSEXUALITY • Treat any underlying syndrome, such as a mania-like state • Consider antiandrogens for men who are dangerously hypersexual or aggressive: Progesterone 5 mg/day orally; adjust dose to suppress testosterone well below normal If patient responds, may treat with 10 mg IM depot progesterone weekly Leuprolide acetate 5–10 mg IM monthly is an alternative 43 S U M M A RY ( 1 o f 2 ) • The need to express basic needs such as hunger, thirst, or fatigue, which the patient cannot adequately communicate in dementia, may precipitate a behavioral disturbance • Delirium secondary to an underlying condition such as dehydration, urinary tract infection, or medication toxicity is a common cause of abrupt behavioral disturbances in patients with dementia 44 S U M M A RY ( 2 o f 2 ) • Medication effects on behavioral disturbances in dementia tend to be modest and should be implemented only after trying environmental and other nonpharmacologic techniques • Antipsychotic medications may reduce agitation, and antidepressants may be helpful if symptoms of depression are evident in the patient with a behavioral disturbance 45 CASE 1 (1 of 4) • An 80-year-old woman is brought to the office because for 6 weeks she has had intermittent severe agitation characterized by shouting, grabbing, and nearly running away from helpful overtures. • The patient has had Alzheimer disease for several years, which is now in the moderate stage. • Medications include donepezil 10 mg/d. She has no adverse effects, and she takes no other psychotropic medications. 46 CASE 1 (2 of 4) • The patient has been living at home with two younger sisters since her husband died 2 years ago. During this time, despite increasing cognitive impairment, the patient has had only occasional emotional outbursts from which she could be distracted easily. • With the onset of severe agitation, her sisters and home-health aides feel overwhelmed. • Physical examination and laboratory findings do not suggest any causes for her agitation. 47 CASE 1 (3 of 4) Which of the following is the most appropriate next step? A. Increase donepezil from 10 mg/d to 23 mg/d. B. Prescribe risperidone 0.25 mg/d. C. Recommend placement in an assisted-living facility or nursing home. D. Inquire further about potential environmental triggers. 48 CASE 1 (4 of 4) Which of the following is the most appropriate next step? A. Increase donepezil from 10 mg/d to 23 mg/d. B. Prescribe risperidone 0.25 mg/d. C. Recommend placement in an assisted-living facility or nursing home. D. Inquire further about potential environmental triggers. 49 CASE 2 (1 of 3) • An 86-year-old man is admitted to a nursing facility. History includes advanced Alzheimer disease. • He had been in a different facility, where he had a history of behavioral disturbances manifested by restlessness, wandering, repetitive vocalizations, and occasionally striking out at caregivers. • His wife says, “They wouldn’t give him anything to calm him down at the other place because of a black box warning.” She wants to know what that means and why nursing homes “won’t give medications to keep people from hitting and scratching.” 50 CASE 2 (2 of 3) Which of the following should form the basis of further discussion? A. Providers are prohibited by law from prescribing a drug that has a black box warning about a potential adverse effect in certain groups of patients. B. Newer second-generation antipsychotic drugs are approved by the FDA to treat dementia-associated behavioral disturbances that pose a threat to others. C. The initial step in addressing the patient’s behavioral disturbances is to understand what triggers them. D. Mood stabilizers such as valproic acid often benefit residents exhibiting similar behavioral disturbances. E. In the nursing facility, judicious use of restraints is an effective intervention for wandering. 51 CASE 2 (3 of 3) Which of the following should form the basis of further discussion? A. Providers are prohibited by law from prescribing a drug that has a black box warning about a potential adverse effect in certain groups of patients. B. Newer second-generation antipsychotic drugs are approved by the FDA to treat dementia-associated behavioral disturbances that pose a threat to others. C. The initial step in addressing the patient’s behavioral disturbances is to understand what triggers them. D. Mood stabilizers such as valproic acid often benefit residents exhibiting similar behavioral disturbances. E. In the nursing facility, judicious use of restraints is an effective intervention for wandering. 52 CASE 3 (1 of 4) • An 84-year-old man with probable Alzheimer disease is admitted to a nursing home for long-term care. • His family believes he can no longer live in his apartment, even with round-the-clock home-health aides, because of irritability and easily triggered aggressive behaviors, including hypersexuality. • The family refuses all psychotropic medication because they are concerned about increased mortality. They allow treatment for dementia, and the patient is given donepezil and memantine, neither of which has improved this behavior. 53 CASE 3 (2 of 4) • The patient continues to have private-duty aides in his first days at the nursing home, and they are largely able to redirect any aberrant behavior. When private assistance is discontinued, his behavior immediately deteriorates: he has angry interchanges with other residents and staff, insists on leaving the facility, and touches female residents inappropriately. • A number of nonpharmacologic approaches fail, and the patient’s family continues to refuse antipsychotic agents. The patient’s community neurologist suggests valproate, which the family is willing to consider because they have read that it may have neuroprotective properties. 54 CASE 3 (3 of 4) Which of the following outcomes is most likely? A. Improvement of behavioral symptoms; no effect on clinical progression Alzheimer disease B. Improvement of behavioral symptoms; delay in clinical progression of Alzheimer disease C. No effect on behavioral symptoms; delay in clinical progression of Alzheimer disease D. No effect on behavioral symptoms; no effect on clinical progression of Alzheimer disease E. Improvement of behavioral symptoms; worsening of clinical progression of Alzheimer disease 55 CASE 3 (4 of 4) Which of the following outcomes is most likely? A. Improvement of behavioral symptoms; no effect on clinical progression Alzheimer disease B. Improvement of behavioral symptoms; delay in clinical progression of Alzheimer disease C. No effect on behavioral symptoms; delay in clinical progression of Alzheimer disease D. No effect on behavioral symptoms; no effect on clinical progression of Alzheimer disease E. Improvement of behavioral symptoms; worsening of clinical progression of Alzheimer disease 56 GNRS4 Teaching Slides Editor: Barbara Resnick, PhD, CRNP, FAAN, FAANP, AGSF GNRS4 Teaching Slides modified from GRS8 Teaching Slides based on chapter by Melinda S. Lantz, MD and questions by Blaine S. Greenwald, MD Managing Editor: Andrea N. Sherman, MS Copyright © 2014 American Geriatrics Society