Pharmacological Treatments for Neuropsychiatric Symptoms in Dementia 3/22/2018
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1 Pharmacological Treatments for Neuropsychiatric Symptoms in Dementia 3/22/2018 Mary Ellen Quiceno, MD, FAAN Associate Professor of Neurology UNTHSC Center for Geriatrics 855 Montgomery Street, PCC 4, Ft. Worth, TX (817) Associate Professor of Medical Education TCU & UNTHSC School of Medicine Texas Council on Alzheimer s Disease and Related Dementias
2 Disclosures Eli Lilly: Speaker s Bureau Adamas: Consultant NIH, Eli Lilly: Research Support Since there are no FDA approved medications for most neuropsychiatric symptoms in dementia, I will discuss off-label prescribing.
3 Objectives Describe different types of dementias in which neuropsychiatric symptoms often occur State when and why the neuropsychiatric symptoms happen Name a common measurement tool used to classify and quantify neuropsychiatric symptoms Understand nonpharmacological approaches that should be tried prior to pharmacological treatment Discuss pharmacological treatments and research ongoing to find new therapies
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5 types-of-dementia.asp
6 AD 5.5 million Americans of all ages have Alzheimer's 200,000 are YOUNGER than age 65 2/3 of Americans with Alzheimer's are women African-Americans are 2x as likely to have Alzheimer's Hispanics are 1.5x as likely to have Alzheimer's
7 CJD 1/1,000,000 cases diagnosed annually <1 year duration
8 FTD ~2/3 are years old 5-10/100,000 Behavior & personality changes early Some present with problems speaking
9 Parkinson s Disease Dementia & Dementia with Lewy Bodies Parkinson ds 1,000,000 in US 10/100,000 at age 50 & 200/100,000 at age 80 Dementia increases with age (65% by age 85) DLB 1,300,000 in US All have dementia
10 Wernicke-Korsakoff Syndrome Related to thiamine (B1) deficiency Alcohol abuse Malnutrition Gastric bypass Hyperemesis gravidarum AIDS
11 Huntington s Disease 1/10,000 in US Onset varies Childhood through late adulthood
12 In Alzheimer disease
13 Onset of Neuropsychiatric Symptoms Disease Early Middle Late Alzheimer x Parkinson disease x Dementia with Lewy Bodies x Frontotemporal disease BV x Frontotemporal disease LV x Frontotemporal disease MV x Creutzfeldt-Jakob disease x Wernicke-Korsakoff x Huntington disease x
14 Emergence of Neuropsychiatric Three phases: Symptoms (1) irritability, depression, and nighttime behavior changes; (2) anxiety, appetite changes, agitation, and apathy; and (3) elation, motor disturbances, hallucinations, delusions, and disinhibition Alzheimer s & Dementia: Translational Research & Clinical Interventions. September 2017; 3(3):
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16 Antecedent Behavior Consequence (ABC) documentation The five Ws of behavior: a. What is the specific behavior? b. Why does this need to be addressed? c. Where does it occur? d. When does it occur? What occurred just before the behavior started? e. Who is around when it happens?
17 NPI-Q Link/CONT/A/CONT_21_3_2015_02_26_KAUFER_ _SDC2.pdf
18 Neurobiology
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20 Classes of Medications Used Antidepressants Antidepressants target the symptoms of depression such as irritability, negativity, anxiety, resistance, agitation, sadness, sleep disturbance, expressions of worthlessness/desire to die, and appetite changes can even include paranoia and other forms of psychosis Mood Stabilizers Mood stabilizers are given to assist in management of mood, agitatio,n and aggression such as Depakote and Neurontin and Tegretol/Trileptal Anti-psychotic Medications Treat the extreme behavioral consequences of dementia They do have serious potential side effects including increased risk of death, increase in parkinsonism, and others First generation or typical antipsychotic medications should be used in low doses and short-term Second generation or atypical antipsychotic medications, such as Risperdal, Zyprexa and Seroquel are preferred is they must be used Newer, non-dopaminergeric targeting anti-psychotic medications, such as pimavanserin, is approved for use in Parkinson disease psychosis
21 Neuropsychiatric Symptoms Psychosis Depression & Apathy Agitation Sleep & Sundowning
22 Psychosis Occurs in older adults with Bipolar disorder Delirium, medications Major Depression Dementia Late-life delusional disorder Metabolic disorders Thyroid, glucose/sodium imbalance, B12/B1 deficiency Pain Schizophrenia Seizures, epilepsy Brain tumors or stroke Alcohol or drug withdrawal About 20%+ of Alzheimer s disease patients More in DLB Delusions may be paranoid People stealing things Spouse unfaithful Hallucinations (~11% of patients) are more commonly visual
23 Increased mortality has been identified with the use of all antipsychotic agents They carry an FDA warning regarding increased all cause mortality in patients with dementia (risk compared to placebo)(4.5% v 2.6% rate of death)(cv or infection)(risk may vary depending on dose)
24 Selective Serotonin (5-HT) 2A Receptor Inverse Agonist Pimavanserin FDA approved treatment for Parkinson s disease psychosis does not block dopamine D2 receptors
25 Mood Disorders: what & why Depression ~40% of AD, even MCI Sadness, loss of interest, anxiety, irritability, decreased appetite Consider social activities Could use antidepressants Watch for SSRI interactions with ACHEI More Common in PDD/DLB, esp with anxiety bvftd may be mistaken for depression initially Decreased serotonin, dopamine, NE?
26 Mood Disorders: what & why Apathy 36-88% of patients with AD; more common in FTD Impairs ADLs Types Affective: indifference or lack of empathy Behavioral: indolence and requirement for prompts to initiate physical activity Cognitive: inactivation of goal-directed cognitive activity Can coexist w/depression cortical dysfunction in the posterior cingulate or inferior temporal cortex; abnormalities in cholinergic, GABAergic, and dopaminergic function
27 Mood Disorders: treatment Depression in Alzheimer s Disease Study (DIADS) improvement with sertraline compared with placebo in patients with AD with major DIADS-2, included patients meeting criteria for depression of AD, but found no differences in depression outcomes Other studies included mirtazapine and SNRIs without improvement in outcome For apathy: Open label studies of cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) showed improvement in apathy for all three medications For PDD, DLB, may need dopaminergic stimulation Treat co-existing depression ACHEI plus Alpha GPC
28 Agitation: what Defined as excessive motor activity, or verbal or physical aggression that is associated with emotional distress (1) severe enough to produce disability; (2) beyond what would be expected from cognitive impairment by itself; (3) not solely attributable to another disorder, environmental conditions, or the physiological effects of a substance Often associated with psychosis, anxiety, and disinhibition
29 Agitation: why Degeneration of the brain regions associated with emotional regulation and salience The frontal, anterior cingulate, and posterior cingulate cortices, amygdala, and hippocampus Decreased acetylcholine & serotonin Psychologically, reduced stress thresholds and unmet needs due to limited communication
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32 Agitation: treatment Educate caregivers Change the physical environment Increase social engagement, exercise and activities Address sleep problems Assessing pain, discomfort, and other medical conditions SSRI, mood stabilizer, antipsychotic may help
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35 Sundowning: what the exacerbation of cognitive symptoms and confusion anxiety, agitation, aggression, pacing, wandering, resistance, screaming, yelling, visual and auditory hallucinations the occurrence or worsening of behavioral disturbances during the late afternoon and early evening, whereas other researchers also consider NPS occurring throughout the night or more vaguely emerging with darkness Front. Med., 27 December 2016
36 Sundowning: why Circadian rhythm disorders involvement of the suprachiasmatic nucleus (SCN), located in the hypothalamus and considered as the major circadian pacemaker of the human body SCN is sensitive to cholinergic stimulation SCN regulates melatonin secretion
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39 Sundowning: treatment
40 In Summary Exclude medical and environmental factors Non-pharmacological interventions should be attempted before moving to drug therapy Symptoms include depression or anxiety selective serotonin reuptake inhibitors, such as antidepressants, are advised Symptoms do not include depression or anxiety AChEIs are first recommended Then atypical antipsychotics Memantine may be helpful, also melatonin, mood stabilizers
41 Agitation in Dementia Research Studies Lithium Prazosin in NH residents* NUEDEXTA (dextromethorphan HBr and quinidine sulfate)
42
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