MANAGING LATE STAGE ALZHEIMER S DISEASE- A PALLIATIVE APPROACH Nakia A. Beard, PharmD, CGP Assistant Professor of Pharmacy Practice, Division of Geriatrics Texas Tech University Health Sciences Center School of Pharmacy Dallas/Fort Worth April 12, 2014 DISCLOSURES The presenter has no actual or potential conflicts of interest to disclose. The presenter may discuss information regarding off-label uses for medications and their current uses in medical and pharmacy practice OBJECTIVES Upon completion of this knowledge-based activity, participants will be able to: Explain management of Alzheimer s including when to consider titration or discontinuation Discuss use of antipsychotics for management of dementia-related psychotic behaviors Given a patient case, create a therapeutic plan for a patient with dementia based on their medication list and other pertinent patient information TSHP 2014 Annual Seminar 1
PATIENT CASE INTRODUCTION 74 year old male PMH: Alzheimer s Dementia x 2 years Hypertension x 12 years Benign Prostatic Hypertrophy x 4 years CVA x 5 years ago Atrial fibrillation x 8 years Insomnia x 3 years Depression x 3 years Recent Information (Past month) Episodes of nausea/vomiting daily Diarrhea Only eats ~ 50% of meals Wandering in the evening Refusing medications in the evening Also states a medication was recently increased, but family cannot remember which medication ADDITIONAL PATIENT INFORMATION Patient s Medications: Lisinopril 20 mg daily Hydrochlorothiazide 25 mg daily Donepezil 10 mg daily Terazosin 4 mg daily Atorvastatin 20 mg daily Metoprolol tartrate 50 mg twice daily Warfarin 5 mg daily Multivitamins daily Tylenol PM 1 tablet daily Citalopram 20 mg daily Recent Labs / Vital Signs SCr = 1.2 mg/dl Lipid Panel = At goal AST/ALT = within normal limits INR = 2.5 BP: 138/72 mmhg Pulse: 58 bpm Weight: 64 kg Height: 5 10 WHERE DO WE BEGIN? TSHP 2014 Annual Seminar 2
Dementia Type TYPES OF DEMENTIAS Prevalenc e Common Signs/Symptoms Alzheimer s Dementia 50 % Gradual onset with continuing decline Social Withdrawal Paranoia Anxiety Not caused by identifiable medical, psychiatric, or neurologic condition Vascular Dementia 25% Focal neurological signs or lab evidence of cerebrovascular condition May have white-matter changes Step-wise decline in cognition Lewy Body Dementia 15% Fluctuating cognitive performance Visual hallucinations History of parkinsonism Dementia from other causes McCullough, et al. Dementia Guideline 2013 5% Evidence from patient s history for a condition causing cognitive deficits Head trauma, HIV, Parkinson s, Huntington s DISEASE STAGES BY MMSE Image from: http://img.medscape.com/fullsize/migrated/editorial/clinupdates/2003/241 0/tangalos.fig1.gif. Accessed September 9, 2013 GOALS OF THERAPY Disease Stage Mild Cognitive Impairment Treatment Goals Maintain function, safety, and independence Reduce or stop medication that may contribute to cognitive decline Early-Stage Dementia Maintain function and independence while preserving safety Reduce or stop medication that may contribute to cognitive decline Mid-Stage Dementia Preserve safety, function,and independence Develop skills to continue living at home and delay institutionalization Late-Stage Dementia Preserve safety, comfort, and dignity End-StageDementia Consider hospice referral McCullough, et al. Dementia Guideline 2013 TSHP 2014 Annual Seminar 3
WHAT DRUGS CAN WE USE? MEDICATION MANAGEMENT OF ALZHEIMER S DEMENTIA FDA Approved Agents for cognitive decline Cholinesterase Inhibitors (AChEI) Donepezil, Rivastigmine, Galantamine, Tacrine* N-methyl-d-aspartate Receptor Antagonist (NMDA) Memantine Symptomatic Treatment (Not FDA Approved for Dementia-Related Behaviors) Depression - Antidepressants Psychosis -Antipsychotics Agitation - Antipsychotics Aggression - Anticonvulsants LET S TALK ABOUT FDA APPROVED TREATMENTS TSHP 2014 Annual Seminar 4
DONEPEZIL (ARICEPT ) Indicated for: Mild-Severe Alzheimer s Dementia Dosage Forms: Tablets Dosing: Initial: 5 mg by mouth daily, increase to 10 mg daily (after 4-6 weeks) Maximum: 23 mg daily Adverse Effects: Gastrointestinal (3 22%) dose-dependent Insomnia (2 14%) - vivid dreams Cardiovascular: Atrioventricular block, bradycardia Administration Nighttime; Take with or without food 23 mg tablets cannot be crushed, split, or chewed Donepezil [package insert]. Feb 2012 GALANTAMINE (RAZADYNE ) Indicated for Mild-Moderate Alzheimer s Dementia Dosage Forms: Solution, Tablet, Extended Release Capsule Dosing IR: 4 mg twice daily x 4 weeks, increase to 8 mg twice daily, then 12 mg twice daily. ER: 8 mg daily x 4 weeks, increase to 16 mg daily, then 24 mg daily. Dose Adjustments Max dose is 16 mg/day if Child-Pugh Score 7-9, or CrCl < 60 ml/min Not recommended for patients with severe renal/hepatic impairment Adverse Effects: Gastrointestinal (9-25%) Cardiovascular: Atrioventricular block, Bradycardia Galantamine [package insert]. July 2013 RIVASTIGMINE (EXELON ) Indicated: Mild-Moderate Alzheimer s Dementia Mild-Moderate Dementia secondary to Parkinson s Disease Dosage Forms: Transdermal Patch Capsule Dose 4.6mg patch daily for 4 weeks, then increase to 9.5mg patch daily. Max Dose: 13.3 mg Adverse Effects: Gastrointestinal (3-12%) Cardiovascular: Arrhythmia, Bradycardia Application Site Reactions Rivastigmine [package insert]. July 2013. Rivastigmine tartrate [package insert]. July 2010. TSHP 2014 Annual Seminar 5
MEMANTINE (NAMENDA ) Indicated for Moderate Severe Alzheimer s Dementia Dosage Forms: Tablets, Solution, Extended-Release (ER) Capsule Dosing: Sol/Tab: 5 mg once daily, and increase in 5-mg increments (at least once weekly) to 10 mg twice daily ER Cap: 7 mg once daily, increase once weekly in 7-mg increments to 28 mg daily Dose Adjustments: If CrCl <30 ml/min, decrease IR to 5 mg BID and ER to 14 mg daily Adverse Effects: Gastrointestinal (2-5%) Neurological: CVA, TIA, Cerebral infarct Renal Acute Renal Failure Memantine [package insert]. October 2013 POSSIBLE RISKS AND BENEFITS Risks Syncope Bradycardia Respiratory Problems Initial Fecal Issues Agitation Seizure Benefits Decreased hip fracture Decreased myocardial infarction (MI) Caregiver peace of mind Delayed nursing home placement Decreased behavioral issues Gill SS, et al. Arch Intern Med. 2009. Nordstrom P, et al. Eur Heart J. 2013. Kroger E, et al. Am J Geriatr Pharmacother. 2012. Tamimi I, et al. J Bone Miner Res. 2012. WHEN TO TITRATE OR TAPER MEDICATIONS? TSHP 2014 Annual Seminar 6
TITRATING/TAPERING MEDICATIONS Facts to Consider Patients Changes in ADL s and cognition Cost of medications Other disease states Willingness to take medications Caregivers Caregiver Burden Time CAREGIVERS Types of Caregivers Family Home-Health Aides/Nurses Provide information Medication Compliance Home Life Desire for medication ADDITIONAL RESOURCES FOR CAREGIVERS The 36-Hour Day: A Family Guide to Caring for Persons with Alzheimer Disease, Related Dementing Illnesses, and Memory Loss in Later Life Living with Alzheimer s Website: http://www.alz.org/living_with_alzheimers_4521.asp Caring for a Patient with Dementia Website: http://james.psych.umn.edu/~grecc/caring.htm Caregiver Resources. http://www.alz.org/national/documents/lib_best_fcare.pdf TSHP 2014 Annual Seminar 7
TITRATION VERSUS TAPERING OFF TITRATION Caregiver s ability to manage side effects Normal or elevated pulse Stable weight Ability to remain compliant TAPERING OFF Lack of effect / Inability to tolerate Refusal of medication No longer eating Hospice care Financial hardship Burns A, et al. Lancet Neurol. 2009. Amuah JE, et al. Pharmacoepidemiol Drug Saf. 2010. Sun Y, et al. Euro J Neurol. 2008. Mansour D, et al. Am J of Geriatr Pharmacother. 2011. HOW DO WE MANAGE OTHER SYMPTOMS? BEHAVIORAL DISORDERS OF COGNITIVE IMPAIRMENT Psychoses Aggression Agitation Apathy Others Hallucinations Delusions Physical Verbal Akathisia Loss of Compulsion interest s Obsessions Sleep Disorders Anxiety Depressio n Loss of self-esteem Guilty What agents do we prescribe or recommend? McCullough, et al. Dementia Guideline 2013 TSHP 2014 Annual Seminar 8
WHEN SHOULD ANTIPSYCHOTICS BE CONSIDERED? Pose an immediate risk of harm to self or others? Due to pain, medical condition/delirium, environmental factors, a personal need? Assess impact on caregiver and housing situation Psychoeducation and goals to maintain housing (additional consultation) Level of patient s behavioral disturbance? Severity Specific Activities Preferred Treatment Mild to Moderate Severe Wandering, flailing limbs, refusing care/medication, outbursts Physical aggression, combativeness, hitting, biting, property destruction Nonpharmacologic Approaches Psychopharmacologic Approaches McCullough, et al. Dementia Guideline 2013 TREATMENT OF BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS Drug Class/Target Symptoms Antidepressants Agitation Depression Anxiety Antidepressants Insomnia Line Medication Initial Dose Max Dose First Escitalopram 2.5 mg daily 10 mg daily First Sertraline 25 mg daily 100 mg daily Second Fluoxetine 5 mg daily 30 mg daily Third Citalopram 5 mg daily 20 mg daily First Trazodone 25-50 mg daily 200 mg daily* Second Mirtazapine 7.5 mg daily 30 mg daily* McCullough, et al. Dementia Guideline 2013 TREATMENT OF BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS Drug Class/Target Symptoms Antipsychotics Delusions Hallucinations Aggression Agitation Antiepileptics Aggression Disinhibition Line Medication Initial Dose Max Dose (Total Daily Dose) First Quetiapine 12.5-25 mg twice daily Secon d Risperidone 0.25-0.5 mg daily (or twice daily) 200 mg daily 2 mg daily Third Olanzapine 2.5-5 mg daily 10 mg daily Fourth Aripiprazole 5 mg daily 15 mg daily First Secon d McCullough, et al. Dementia Guideline 2013 Divalproex (delayed release) Carbamazepin e 125 mg daily 1,000 mg daily 100 mg daily 600 mg daily TSHP 2014 Annual Seminar 9
Daily DoseThresholds for Antipsychotic Medications Used to Treat BPSD Generic Name MaximumTotal Daily Dose (mg) Chlorpromazine 75 Fluphenazine 4 Haloperidol 2 Aripiprazole 10 Olanzapine 5 Quetiapine 150 Risperidone 2 CMS Memo 5.24.2013 NOW LET S GO BACK TO OUR PATIENT PATIENT CASE INTRODUCTION 74 year old male PMH: Alzheimer s Dementia x 2 years Hypertension x 12 years Benign Prostatic Hypertrophy x 4 years CVA x 5 years ago Atrial fibrillation x 8 years Insomnia x 3 years Depression x 3 years Recent Information (Past month) Episodes of nausea/vomiting daily Diarrhea Only eats ~ 50% of meals Wandering in the evening Refusing medications in the evening Also states a medication was recently increased, but family cannot remember which medication TSHP 2014 Annual Seminar 10
ADDITIONAL PATIENT INFORMATION Patient s Medications: Lisinopril 20 mg daily Hydrochlorothiazide 25 mg daily Donepezil 10 mg daily Terazosin 4 mg daily Atorvastatin 20 mg daily Metoprolol tartrate 50 mg twice daily Warfarin 5 mg daily Multivitamins daily Tylenol PM 1 tablet daily Citalopram 20 mg daily Recent Labs / Vital Signs SCr = 1.2 mg/dl Lipid Panel = At goal AST/ALT = within normal limits INR = 2.5 BP: 138/72 mmhg Pulse: 58 bpm Weight: 64 kg Height: 5 10 CASE QUESTIONS What are some other questions that you would like to ask this patient or the patient s caregiver? What medications are potentially inappropriate? What is the cause of the nausea, vomiting, and diarrhea? What changes in therapy would you make or recommend for this patient? Would you consider adding an antipsychotic to this patient? What if we made some changes to this patient case? IN SUMMARY Very few medications are FDA-approved for management of cognitive disorders Discussed various factors to consider when discontinuing or titrating medications for Alzheimer s dementia Identified instances when and when not to use antipsychotics for the management of Behavior and Psychological Symptoms of Dementia Identified medications that may worsen dementia Discussed some resources to help caregivers to care for patients with Alzheimer s Dementia TSHP 2014 Annual Seminar 11
ANY ADDITIONAL QUESTIONS? THANK YOU! If you have additional questions, please feel free to contact me at Nakia.beard@ttuhsc.edu REFERENCES McCullough, et al. Dementia and Cognitive Impairment Diagnosis and Treatment Guideline. December 2012 Bareham, et al. Assessing medication appropriateness in the elderly: using Beer s and STOPP START Criteria. May 2013 Donepezil [package insert]. Pfizer Inc., New York, NY; February 2012. Galantamine [package insert]. Janssen Pharmaceuticals, Inc., Titusville, NJ; July 2013. Rivastigmine [package insert]. Novartis Pharmaceuticals Corporation, East Hanover, NJ; July 2013. Rivastigmine tartrate [package insert]. Watson Laboratories, Inc, Corona, CA; July 2010. Memantine [package insert]. Forest Pharmaceuticals, Inc. St. Louis, MO; October 2013. Gill SS, Anderson GM, Fischer HD, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med. 2009;169(9):867-73. Nordström P, Religa D, Wimo A, Winblad B, Eriksdotter M. The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer's disease. Eur Heart J. 2013;34(33):2585-91. Kröger E, Berkers M, Carmichael PH, Souverein P, Van marum R, EgbertsT. Use of rivastigmine or galantamineand risk of adverse cardiac events: a database study from the Netherlands. Am J Geriatr Pharmacother. 2012;10(6):373-80. Tamimi I, OjeaT, Sanchez-siles JM, et al. Acetylcholinesterase inhibitors and the risk of hip fracture in Alzheimer's disease patients: a case-control study. J Bone Miner Res. 2012;27(7):1518-27. TSHP 2014 Annual Seminar 12
REFERENCES Alzheimer s Association. Caregiver Resources. http://www.alz.org/national/documents/lib_best_fcare.pdf. Accessed on February 24, 2013. Burns A, Bernabei R, Bullock R, et al. Safety and efficacy of galantamine (Reminyl) in severe Alzheimer's disease (the SERAD study): a randomised, placebo-controlled, double-blind trial. Lancet Neurol. 2009;8(1):39-47. Amuah JE, Hogan DB, Eliasziw M, et al. Persistence with cholinesterase inhibitor therapy in a populationbased cohort of patients with Alzheimer's disease. Pharmacoepidemiol Drug Saf. 2010;19(7):670-9. Sun Y, Lai MS, Lu CJ, Chen RC. How long can patients with mild or moderate Alzheimer's dementia maintain both the cognition and the therapy of cholinesterase inhibitors: a national population-based study. Eur J Neurol. 2008;15(3):278-83. Mansour D, Wong R, Kuskowski M, Dysken M. Discontinuation of acetylcholinesteraseinhibitor treatment in the nursing home. Am J Geriatr Pharmacother. 2011;9(5):345-50. Risperidone [package insert]. Janssen Pharmaceuticals, LLC. Titusville, NJ: August 2012 Medicare atypical antipsychotic drug claims for elderly nursing home residents. HHS OIG Report May 2011. Accessed online at: http://oig.hhs.gov/oei/reports/oei-07-08-00150.pdf. Accessed February 10, 2014. Dementia in Nursing Homes: Clarification to Appendix P SOM and Appendix PP in the SOM for F309 and F329. Centers for Medicare and Medicaid Services. May 24, 2013. TSHP 2014 Annual Seminar 13