What s new for diagnosing and treating Parkinson s Disease? Erika Driver-Dunckley, MD Associate Professor of Neurology Program Director Movement Disorders Fellowship Assistant Program Director Neurology Residency Program Department of Neurology Mayo Clinic Arizona Disclosures: none
Resources: PMD Alliance http://www.pmdalliance.org/ MJFF https://www.michaeljfox.org/ PDF http://www.pdf.org/ NPF http://www.parkinson.org/ Davis Phinney Foundation https://www.davisphinneyfounda tion.org/
Biomarker: PD vs Parkinsonism? Blood test: Neurofilament light chain (NfL) increased in Parkinsonism, decreased in PD
What is the DaTscan? FDA approved in 2011 (Europe 2000) Ioflupane I 123 injection with SPECT imaging Ioflupane has high affinity for pre-synaptic dopamine transporters(dat) Qualitative interpretation Possible side effects: headache, nausea, vertigo Contraindications: pregnant or breast feeding Relative contraindication: Iodine allergy Sensitivity 98% Specificity 67% ONLY FDA approved for Parkinsonism vs ET Cost: ~$2000. Covered by insurance
Parkinson s Disease Medications Carbidopa/Levodopa Carb/levo IR 25/100, 10/100, 25/250 Carb/levo CR 25/100, 50/200 Stalevo (carb/levo/entacapone) Rytary (carb/levo) Duopa (carb/levo) Dopamine Agonists Mirapex (Pramipexole), CR Requip (Ropinirole), XL Neupro (Rotigotine) Apokyn (Apomorphine) MAO-B Inhibitors Eldepryl (Selegiline) Azilect (Rasagiline) COMT Inhibitors Comtan (Entacapone) Tasmar (Tolcapone) Anti-cholinergics Cogentin (Benztropine) Artane (Trihexyphenidyl) MAO-B Inhibitor/DA reuptake Inhibitor Xadago (Safinamide) NMDA antagonist/da reuptake Inhibitor Symmetrel (Amantadine) Surgery Anti-psychotics Seroquel (Quetiapine) Clozaril (Clozapine) Nuplazid (Pimavanserin)
Rytary Impax Laboratories January 2015 FDA approved For early, moderate and advanced PD, parkinsonisms Oral extended-release therapy with C-L (1:4) microbeads Microbeads dissolve at various rates that allows for quick absorption and sustained L-dopa release over an extended period Can be sprinkled over applesauce Should avoid taking with meals
Rytary dosing Recommended starting dosage (L-dopa naïve patients) 23.75mg/95mg 1 tab TID for 3 days then 36.25mg/145mg 1 tab TID The dosing frequency may be changed from three times a day to a maximum of five times a day if more frequent dosing is needed and if tolerated. The maximum recommended daily dose of Rytary is 612.5 mg / 2450 mg.
Sinemet to Rytary conversion table
Adverse reactions Rytary: Warnings Early Parkinson s disease: Most common are nausea, dizziness, headache, insomnia, abnormal dreams, dry mouth, dyskinesia, anxiety, constipation, vomiting, and orthostatic hypotension. Advanced Parkinson s disease: Most common are nausea and headache. Contraindications Nonselective MAO inhibitors
Duopa AbbVie Inc FDA approval Jan 2015 In Europe since 2004 Enteral suspension of carb/levo
Duopa Approved for Advanced PD (motor fluctuations) 16 hr infusion via PEG-J Max dose is 2000mg L-dopa/day May still take oral carb/levo Consider before DBS
Adverse reactions Duopa: Warnings Most common: complication of device insertion, nausea, depression, peripheral edema, hypertension, upper respiratory tract infection, throat pain, and incision site erythema. Contraindications DUOPA is contraindicated in patients taking nonselective monoamine oxidase (MAO) inhibitors.
Acadia Pharmaceuticals Nuplazid FDA approved April 2016 ONLY FDA approved rx for PD psychosis (hallucinations and delusions) SSIA (selective serotonin inverse agonist: 5-HT 2A and 5-HT 2C ) Does not impair motor functioning
Nuplazid - dosing Dosage Forms & Strengths 17 mg tablet 34 mg PO qday (without titration) Dosage Modifications Coadministration with strong CYP3A4 inhibitors Decrease dose to 17 mg PO qday Coadministration with strong CYP3A4 inducers Monitor for reduced efficacy; an increase in pimavanserin dosage may be needed Renal impairment Mild-to-moderate (CrCl 30 ml/min): No dosage adjustment required Severe (CrCl <30 ml/min): Not evaluated Hepatic impairment Not recommended (not evaluated)
Nuplazid adverse reactions QT Interval Prolongation NUPLAZID prolongs the QT interval. The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval. NUPLAZID should also be avoided in patients with a history of cardiac arrhythmias Adverse reactions most common: peripheral edema, nausea, confusional state, hallucination, constipation, and gait disturbance.
Nuplazid: FDA black box warning WARNING: 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. NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson s disease psychosis.
Safinamide (Xadago) Newron Pharmaceuticals March 21 st, 2017 FDA approved A MAO-B inhibitor and dopamine reuptake inhibitor Indicated as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson s disease experiencing off episodes. Patients experienced more beneficial on time, without troublesome uncontrolled involuntary movement (dyskinesia), compared to those receiving a placebo. The increase in on time was accompanied by a reduction in off time.
Safinamide (Xadago): Warnings Adverse reactions Most common adverse reactions were dyskinesia, falls, nausea, and insomnia Contraindications XADAGO is contraindicated in patients with: Concomitant use of the following drugs: Other monoamine oxidase inhibitors or other drugs that are potent inhibitors of monoamine oxidase (e.g., linezolid) Opioid drugs (e.g., tramadol, meperidine and related derivatives); selective norepinephrine reuptake inhibitors; tri-or tetra-cyclic or triazolopyridine antidepressants; cyclobenzaprine; methylphenidate, amphetamine, and their derivatives; St. John s wort Dextromethorphan A history of a hypersensitivity to safinamide Severe hepatic impairment
Aerobic exercise as Neuroprotective? Exercise protects against dopamine cell death in animal models Increases availability of neurotrophic factors (NTFs) Angiogenesis Microglial activation Inhibition of apoptosis Increased mitochondrial respiration
Exercise induced Neuroplasticity
Questions?