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Geriatrics PRN Focus Session—Shakin’ Not Stirred: Movement Disorder Assessment and Management Activity Number: 0217-0000-16-128-L01-P, 1.50 hours of CPE credit; Activity Type: A Knowledge-Based Activity
Monday, October 24, 2016 3:15 p.m. to 4:45 p.m. Great Hall 6
Moderator: Scott Martin Vouri, Pharm. D., MSCI, FASCP, BCPS, CGP Assistant Professor, St. Louis College of Pharmacy, St. Louis, Missouri
Agenda
3:15 PM
4:00 PM
Assessment and Management of Non-Parkinson Movement Disorders Melody Ryan, Pharm. D., MPH, FCCP, BCPS, CGP Professor, University of Kentucky College of Pharmacy, Lexington, Kentucky
Assessment and Management of Movement Disorders with Cognitive and Psychiatric Features Jack. J. Chen, Pharm. D., FCCP, FASHP, FCPhA, BCPS, CGP Professor and Chair, Department of Pharmacy Practice, College of Pharmacy, Marshall B. Ketchum University, Fullerton, California
Conflict of Interest Disclosures Jack J. Chen: Consultancies: (Ipsen), Clinical Investigator: (Lundbeck, LLC), Speaker’s Bureau: (ACADIA Pharmaceuticals), Grants: (Lundbeck, LLC) Scott Martin Vouri: no conflicts to disclose Melody Ryan: no conflicts to disclose
Learning Objectives 1. Compare and Contrast Idiopathic Parkinson’s Disease with drug-induced movement disorders, Essential
Tremor, and Restless Legs Syndrome.2. Discuss best practices for the assessment and management of drug-induced movement disorders.3. Select and Recommend drug and non-drug therapies available to help manage symptoms of Essential
Tremor.4. Select and Recommend drug and non-drug therapies available to help manage symptoms of Restless
Legs Syndrome.5. Compare and Contrast signs and symptoms of Lewy Body Dementia, Parkinson’s Disease Dementia, and
Huntington’s Disease.6. Apply clinical pearls for the management of Lewy Body Dementia.7. Apply clinical pearls for the management of Parkinson’s Disease Dementia.8. Apply clinical pearls for the management of Huntington’s Disease.9. Apply clinical pearls for the management of movement disorders at the end-of-life.
Self-Assessment Questions
Self-assessment questions are available online at www.accp.com/am
• Upper limbs 95%; head 34%, lower limbs 30%, voice 12%, tongue 7%, face 5%, trunk 5%
• Difficulty with writing, drinking, eating, dressing, etc.
• Gait and balance can be affected• Cognitive and psychiatric problems are sometime seen• Pathophysiology unclear, but often hereditary• Alcohol decreases tremor amplitude in 50-90% of cases
• Mechanism unknown, but may involve GABA-A receptorsZesiewicz TA, et al. Neurology 2005;64:2008-20.Louis ED. Curr Opin Neurol 2014;27:461-7.
• FG is a 47-yo M seen in the neurology clinic with an urge to move his legs, most often occurring in the evening. This restless feeling abates when he does move.
• He is currently taking sertraline 50 mg QAM and quetiapine 50 mg QHS for depression, which has been responsive.
• Choose non-dopaminergic agent or lowest dose for shortest time
• Intermittent treatment, if possible
• Treatment• Check serum ferritin and correct if < 50-75 mcg/mL• Use longer acting dopamine agonists• Divide and/or advance the dose• Switch to gabapentin• Switch to low dose, long-acting opioid
Garcia-Borreguero D, et al. Sleep Med 2016;21:1-11.
NINDS-NIMH: National Institute of Neurological Disorders and Stroke-National Institute of Mental Health.1. Ravina B, et al. Mov Disord. 2007;22:1061-1068.
1. Occurs in patients with established diagnosis of PD
2. At least 1 symptom of: hallucinations, illusions, false sense of presence,
delusions
3. Symptoms present for at least 1 month
4. May occur with or without: dementia, insight, PD drugs
Differential diagnoses:
1. Psychosis due to delirium, depression, dementias, schizophrenia,
Management of Hallucinosis and Psychosis in Parkinson’s Disease1. Rule out 2º causes: environment, fluid/electrolyte disturbances, hypoxemia, infection, pain,
medication toxidrome
2. Simplify antiparkinsonian regimen as much as possible by discontinuing or reducingdosage of medications with the highest risk and least benefit.a. Discontinue anticholinergics, including other nonparkinsonian meds with anticholinergic
3. Consider atypical antipsychotic medication if disruptive symptoms persist.
a. Pimavanserin 34 mg qd (FDA approved)a. Quetiapine 12.5–25 mg at qhs; increase 25 mg each week until improve or side effectsb. Clozapine 12.5–50 mg at qhs; increase 25 mg each week until improve or side effects
Association of Antipsychotic Use With Mortality Risk in Patients With PD.
JAMA Neurol. 2016 May 1;73(5):535-41. Weintraub D, Chiang C, Kim HM, et al.
OBJECTIVE: To determine whether AP use in patients with PD is associated with increased mortality.DESIGN: Retrospective matched-cohort study; VA database 1999 to 2010. Rates of 180-day mortality compared in 7877 patients initiating AP therapy and 7877 patients who did not initiate AP therapy (matched for age, sex, race, index year, presence and duration of dementia, PD duration, delirium, hospitalization, Charlson Comorbidity Index, and new nonpsychiatric medications).RESULTS: Antipsychotic use associated with more than twice the hazard ratio (HR) of death compared with nonuse (ITT HR, 2.35; 95% CI, 2.08-2.66; P < .001). The HR was significantly higher for patients who used typical vs atypical APs (ITT HR, 1.54; 95% CI, 1.24-1.91; P < .001). Among the atypical APs used, HRs relative to nonuse of APs in descending order were 2.79 (95% CI, 1.97-3.96) for olanzapine, 2.46 (95% CI, 1.94-3.12) for risperidone, and 2.16 (95% CI, 1.88-2.48) for quetiapine fumarate.
Images of a simple structural formula are ineligible for copyright and therefore in the public domain, because it consists entirely of information that is common property and contains no original authorship.
Types of Movement Disorders with Dementia & Parkinsonism
• Lewy Body Dementias• Parkinson’s disease dementia (PDD)• Dementia with Lewy Bodies (DLB)
• Others• Huntington’s disease• Alzheimer’s with parkinsonism• Corticobasal degeneration (CBD)• Progressive supranuclear palsy (PSP)• Vascular dementia with parkinsonism• FTD with parkinsonism• Dementia-parkinsonism-ALS• And more
* 331.82 codes for both DLB and PDD**Diagnosis 332.0 (PD) had to have a diagnosis code of 331.0 (AD) on the same claim to be considered Lewy Body.†Other dementia includes Creutzfeldt-Jakob disease, Huntington's Chorea, and drug-induced dementia
60-yr-old woman with depressed mood, negative thoughts, mood-congruent delusions, & visual hallucinations (animals). Mild bradykinesia & rigidity noted; treated as psychomotor symptoms of MDD. Diagnosed MDD with psychotic features; olanzapine + duloxetine given. Also on: gabapentin; tramadol/APAP. Olanzapine increased 10 mg QD due to lack of 5 mg response. Days later, found to be confused with rigidity, dysphagia, masked face, and shuffling gait. Eventually admitted: persistent confusion, tachycardia (137 bpm), severe perspiration, elevated body temperature (38.2°C), severe rigidity; elevated CPK of 5,270 U/liter with leukocytosis (WBC 14,600). Diagnosed NMS.
Workup excluded CNS infection, endocrine problems, and other drug-related toxic effects. Treated with supportive, baclofen, clonazepam, bromocriptine. After NMS resolution, persistent fluctuation in cognitive fxn, recurrent visual hallucinations, and parkinsonism evident. Also, repeated falls & persecutory delusions. Striatal DAT SPECT scan abnormal bilaterally. Diagnosed Probable DLB
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS. ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS TREATED WITH ANTIPSYCHOTIC DRUGS ARE AT AN INCREASED RISK OF DEATH. ANALYSES OF SEVENTEEN PLACEBO-CONTROLLED TRIALS (MODAL DURATION OF 10 WEEKS), LARGELY IN PATIENTS TAKING ATYPICAL ANTIPSYCHOTIC DRUGS, REVEALED A RISK OF DEATH IN THE DRUG-TREATED PATIENTS OF BETWEEN 1.6 TO 1.7 TIMES THE RISK OF DEATH IN PLACEBO-TREATED PATIENTS. OVER THE COURSE OF A TYPICAL 10-WEEK CONTROLLED TRIAL, THE RATE OF DEATH IN DRUG-TREATED PATIENTS WAS ABOUT 4.5%, COMPARED TO A RATE OF ABOUT 2.6% IN THE PLACEBO GROUP. ALTHOUGH THE CAUSES OF DEATH WERE VARIED, MOST OF THE DEATHS APPEARED TO BE EITHER CARDIOVASCULAR (e.g., HEART FAILURE, SUDDEN DEATH) OR INFECTIOUS (e.g., PNEUMONIA) IN NATURE. OBSERVATIONAL STUDIES SUGGEST THAT, SIMILAR TO ATYPICAL ANTIPSYCHOTIC DRUGS, TREATMENT WITH CONVENTIONAL ANTIPSYCHOTIC DRUGS MAY INCREASE MORTALITY. THE EXTENT TO WHICH THE FINDINGS OF INCREASED MORTALITY IN OBSERVATIONAL STUDIES MAY BE ATTRIBUTED TO THE ANTIPSYCHOTIC DRUG AS OPPOSED TO SOME CHARACTERISTIC(S) OF THE PATIENTS IS NOT CLEAR. Insert drug name IS NOT APPROVED FOR THE TREATMENT OF PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS (see WARNINGS).
1. Stinton C, et al. Am J Psychiatry. 2015 Aug 1;172(8):731-42.2. Pagano G, et al. J Neurol Neurosurg Psychiatry. 2015;86(7):767-73.3. Yasue I. J Alzheimers Dis. 2015;50(3):733-40.4. Li Y, et al. Cochrane Database Syst Rev. 2015 Mar 3;(3):CD009444.
Huntington’s disease• Juvenile to adult onset• Diagnosis: Family history + clinical sxs or genetic >35 CAG repeats• Motor and psychiatric clinical features:
• Chorea is a hallmark• Bradykinesia, rigidity, dystonia, tics, myoclonus, spasticity• Dementia, hallucinations, psychosis• Aggression, anxiety, apathy, depression, mania, OCD
“…there were no statistically significant differences between the various groups with regard to adverse effects. Our findings demonstrate that, aside from the need for a longer titration in the ultrarapid metabolizers, there are no distinguishing features of patients with various CYP2D6 genotypes, and therefore the current recommendation to systematically genotype all patients prescribed more than 50 mg/day of tetrabenazine should be reconsidered.”
With permission: Mehanna R et al. Mov Disord. 2013;28(2):210-5.
Examples of clocks drawn by the three HD mutation carriers. Participants were asked to draw a clock, and set the time at 10 past 11. MMSE = mini‐mental state examination; UHDRS‐m = Unified Huntington's Disease Rating Scale motor section; TFC = Total Functional Capacity.
2016 ACCP Annual Meeting
Conclusions• Treatment of these neurodegenerative conditions of
interest can be challenging due to:• Evidence gaps in efficacy and tolerability for various
dementia phenotypes• Variability in disease phenotype; concurrent symptoms• Drug-disease interactions
• E.g., antipsychotics worsening parkinsonism• E.g., TBZ worsening other HD symptoms
• New drugs:• Recently, pimavanserin approved for PD psychosis• Inverse agonist at serotoninergic 5-HT2A receptors• Role in DLB and other conditions remains TBD