10/4/2016. Disclosures. Motor symptoms are Just the tip of the iceberg. Parkinson s Disease for the Primary Care Clinician

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1 Disclosures Parkinson s Disease for the Primary Care Clinician Maya Katz, M.D. Assistant Professor of Neurology Movement Disorder and Neuromodulation Center UCSF Medical Center Consulting services for Bagatto, Inc. to guide the development of improved deep brains stimulation clinician programming systems Consulting services for Putnam Associates and Gerson Lehrman Group to help identify treatment gaps for people with Parkinson s disease Consulting services for Cowen and Company, LLC to understand physician perspectives on current and future treatments for people with Parkinson s disease Parkinson s disease Diagnostic Criteria: UK Brain Ban Step 1 Step 2 MOTOR SYMPTOMS Bradykinesia and either rest tremor (4-6 Hz tremor), rigidity or postural instability EXCLUSION CRITERIA e.g. history of repeated strokes or TBI, h/o neuroleptic treatment at symptom onset, cerebellar signs, or nonresponsiveness to levodopa, early severe autonomic involvement, early and severe dementia Step 3 SUPPORTIVE CRITERIA (at least 3) e.g, history of unilateral onset and persistent asymmetry of symptoms, % responsiveness to levodopa, presence of dyskinesias, clinical course for > 10 years, levodopa response for 5 years or more Hughes et al. 2001, Neurology Motor symptoms are Just the tip of the iceberg Langston, 2006, Ann Neurol 1

2 Orthostatic hypotension maintain hydration (fluid with sugar and salt preferred) adding more salt to the diet changing positions slowly midodrine fludrocortisone pyridostigmine (preferred for patient s with supine hypertension) droxidopa Constipation daily prune juice, stay hydrated avoid fiber supplements probiotics miralax 1-2 times daily and senna daily (up to 8 tabs daily) docusate is ineffective can add dulcolax oral or suppository, if needed enema if needed Urinary urgency urology evaluation for BPH trospium or darifenacin myrbetriq intravesicular botulinum toxin sacral nerve stimulation tibial nerve stimultion Erectile dysfunction medication review (SSRIs or SNRIs) wellbutrin or mirtazapine could be considered viagra (generic sildenafil is less expensive) Eyelid opening apraxia botulinum toxin injections every 3 months REM Behavior Disorder (RBD) melatonin 3-12mg one hour prior to bedtime clonazepam Poor sleep maintenance discuss good sleep hygiene rule out OSA melatonin mirtazapine trazadone clonazepam Sensory Loss of smell/taste eating more flavorful, spicy foods Pain NSAIDs and intra-articular steroid injections for arthritic pain cymbalta/venlafaxine for neuropathic pain acupuncture baclofen for dystonic pain botulinum toxin for dystonic pain opiates for neuropathic pain or other refractory pain 2

3 Dysphagia chin tuck alternate between a bite of food and a sip of beverage small bites of food, chew thoroughly mindful eating avoid dry foods referral to speech language pathologist we do not typically use thickeners since these make liquids taste awful; it depends on the patients goals of care Sialorrhea botulinum toxin (myobloc) atropine solution on swab into mouth glycopyrrolate Psychiatric Fatigue ritalin provigil acupuncture Depression/Anxiety mirtazapine escitalopram sertraline duloxetine psychotherapy MBSR/gratitude therapy ECT Pseudobulbar affect SSRI nuedexta Apathy behavioral therapy Psychosis behavioral/environmental interventions cholinesterase inhibitor pimavanserin clozaril Parkinson s disease: Clinical course Cognitive deficits Executive dysfunction Impaired attention Impaired visuo-spatial function Relative preservation of anterograde memory Mild cognitive impairment Dementia Cognitive treatments Cognitive leisure activities Medication review Cholinesterase inhibitors Stage 1: ~2 years Unilateral involvement Stage 2: ~7 years Mild bilateral involvement Stage 4: ~2 years Severe disability, Needs an assistive device to walk or stand Stage 3: ~2 years Mild to moderate bilateral involvement, Postural instability, Still independent Stage 5: ~2 years Wheelchair bound or bedridden Can only ambulate with another person assisting Zhao et al. 2010, Mov Disord 3

4 PD Treatments: Role of exercise PD Treatment: Medications Carbidopa/Levodopa: Dosing Guidelines Exercise daily Exercise at least 150 minutes per week Stretching, Balance, Strengthening and Aerobic exercise LSVT BIG or PWR! Physical Therapy Oguh et al. 2014, Parkinsonism and Related Disorders, Shu et al. 2014, PLOS, Yang et al. 2014, PLOS, Sharp and Hewitt, 2014, Neurosci Biobehav Rev; Posar et al. 2016, Poster at WPC Meeting Start with sinemet 25/100mg IR: ½ tab three times per day Increase to sinemet 25/100mg IR: 1 tab three times per day after 2 weeks Increase to sinemet 25/100mg IR: 1.5 tabs three times per day after 2 weeks Increase to sinemet 25/100mg IR: 2 tabs three times per day after 2 weeks Instruct patients to increase the dose of sinemet only if motor symptoms are not well controlled on the lower dose Can ultimately increase the dose up to 3.5 tabs three times per day, if needed No maximum total daily dose, based on need and tolerance Advanced PD patients may take sinemet every 90 minutes PD Treatment: Medications Carbidopa/Levodopa Extenders: Mechanism of Action PD Treatments: Levodopa sparing therapy Dopamine agonists Zonisamide Rasagaline (Azilect) Selegiline (Eldepryl) Entacapone (Comtan) Tolcapone (Tasmar) Trihexyphenidyl (Artane) Amantadine MAO-B inhibitor (Selegiline or Rasagaline) Najib 2001, Clinical Therapeutics, Youdim 2006, Nature Rev 4

5 Parkinson s disease medications: Tips People with Parkinson s disease need to take their medications at the EXACT times the medications are prescribed, and ideally one hour prior to meals. Dopaminergic medications and cholinesterase inhibitors are essential to comfort for PD patients and should be continued when someone gets hospitalized or enters hospice Avoid: Prochlorperazine (Compazine) Promethazine (Phenergan) Metoclopramide (Reglan) Benzodiazepines (except to treat RBD) Most anticholinergics (e.g. benadryl or oxybutynin) Most antipsychotics (only quetiapine, clozaril and pimavanserin are safe) PD Treatments: Duopa Infusion Intestinal infusion of dopamine (levodopa) Reduces off-medication time Can reduce dyskinesias Has been available in Europe for > 10 years Possible side effects: Tubing issues Otherwise same as oral L-dopa PD Treatments: Deep brain stimulation (DBS) Permanently implanted brain pacemaker 1. Lead 2. Extension Wire 3. IPG Palliative Care for Parkinson s Disease UCSF Parkinson s Disease Supportive Care Clinic Maya Katz, Site Principal Investigator , maya.katz@ucsf.edu 5