Medical Management of Parkinson Disease

Educational Objectives

The goal of this program is to improve the management of Parkinson disease. After hearing and assimilating this program, the clinician will be better able to:

1. Outline medications currently being used in the management of PD.
2. Describe treatment options for nonmotor symptoms of PD.

Summary

Introduction: the rate of production of new medications has increased in the last 10 yr; initial medical therapy varies according to provider and patient preference; providers typically start treatment with levodopa preparations, dopamine agonists, MAO-B inhibitors, and for those with tremor-predominant symptoms, anticholinergic medications can be considered first

Levodopa: one study of medications showed this has small but persistent mobility benefits over other drugs; a study found motor fluctuations and dyskinesia are associated with longer disease duration, and higher levodopa daily dose, rather than the duration of levodopa therapy

Dopamine agonists: there are many formulations; advantages — more reliable extended-release versions are a "nonlevodopa alternative" for patients who are hesitant to take levodopa, and there is less risk for dyskinesia; drawbacks — they have a less robust benefit in response; 40% of individuals develop impulse control disorders, and they can cause withdrawal symptoms, particularly in those with impulse-control disorders, with, eg, panic attacks, anxiety, irritability, diaphoresis

MAO-B inhibitors: drugs such as rasagiline were initially thought to have some neuroprotective effects with early commencement, but recent data have disproved this

Recently Developed Medications

Rytary: this is a carbidopa-levodopa extended release drug; it improves daily off time by >1 hr; it is not a substitute for more advanced surgical therapies

Duopa pump: carbidopa-levodopa in a gel form is put into a cartridge for use in a pump; it requires a specialized percutaneous gastrostomy and jejunostomy (PEG-J) tube because it involves jejunal infusion and absorption; it is recommended for 12 hr/day infusion; a bolus dose is given, followed by a basal infusion that is titrated; PRN boluses may be given; neuropathy from vitamin B12 deficiency, and hyperhomocysteinemia are possible complications; B12, folate, and vitamin B6 supplementation could be considered in patients

Levodopa inhalation powder: this works fast; in the first 10 min the patients start to have an improvement of 5 to 6 points in the Unified Parkinson’s Disease Rating Scale, and the improvement peaks from 30 min to 1 hr; the capsules are crushed and put in an inhaler; it is not for use in patients with restrictive or obstructive lung disease

Apomorphine: this is a D1 and D2 agonist; it comes in a pen with an injector; is for sudden off periods; it can cause nausea and orthostatic hypotension; patients usually have to premedicate with trimethobenzamide for at least 3 days prior to their first test dose, which has to be done under supervision; there is a sublingual version that is fast acting and has a short duration; it is not absorbed if swallowed

Safinamide: this is an MAO-B inhibitor; is an add-on therapy for dopamine agonists and levodopa in mid to late disease; it is not to be used with other MAO inhibitors because of the risk for hypertensive crisis

Opicapone: this is a long-lasting entacapone; it is a catechol-O-methyltransferase (COMT) inhibitor; it lengthens the life of levodopa; it cannot be taken with food

Istradefylline: this is a selective adenosine A2A receptor antagonist; it is related to caffeine; adverse effects include dyskinesia and nausea; it decreases the off time by 5% and decreases motor fluctuations; the dose is increased in patients with high nicotine use

Extended-release of amantadine: this is an N-methyl-d-aspartate receptor antagonist; it possibly enhances the release of catecholamines and inhibits catecholamine reuptake; it is most currently used for dyskinesias; common side effects include dry mouth, nausea, decreased appetite, insomnia, orthostatic hypotension, and livedo reticularis; time without troublesome dyskinesia is increased by 3 hr

Medications for freezing of gait (FOG): there are no specific medications approved by the Food and Drug Administration for FOG; FOG can be divided into levodopa-responsive and levodopa-nonresponsive; levodopa responsive forms are treated by increasing levodopa; other drugs that caused some improvement include dopamine agonists, MAO-B inhibitors, and adenosine antagonists; selective serotonin reuptake inhibitors (SSRIs) were used for patients with concomitant FOG and depression in one study and showed an improvement in these; botulinum toxin showed no improvement for FOG, but limb and joint dystonia, tremor, camptocormia, Pisa syndrome, blepharospasm, and constipation are indications for its use in Parkinson disease

Treatment of Nonmotor Symptoms of PD

Sialorrhea: botulinum toxin A and B, glycopyrrolate, and scopolamine and atropine drops (off-label) can be effective; glycopyrrolate can have some systemic effect and cause constipation and altered mental status

PD dementia: donepezil and galantamine could be used

PD psychosis: clozapine and quetiapine are commonly used; side effects of quetiapine can include sedation, orthostasis, a paradoxical response, and long QT syndrome; drawbacks of clozapine include difficulty with prescribing, a need for weekly complete blood count for the first 6 mo; pimavanserin is a new medication for PD psychosis; it is an inverse agonist of the serotonin 5-HT2A receptor; side effects include peripheral edema, nausea, confusion, and long QT syndrome; it takes 4 to 6 wk to take full effect, so this may require bridging

Readings

Cerri S, Blandini F. An update on the use of non-ergot dopamine agonists for the treatment of Parkinson's disease. Expert Opin Pharmacother. 2020;21:2279-2291; doi: 10.1080/14656566.2020.1805432; Jost WH. Use of botulinum neurotoxin in Parkinson's disease: a critical appraisal. Toxins (Basel). 2021;13:87; doi: 10.3390/toxins13020087; McKay J, et al. Anxiety and depression are associated with levodopa-responsive, but not levodopa-unresponsive, freezing of gait in Parkinson's disease (P2. 8–031). Neurology 2019;92:P2.8-031; Orayj K, et al. Factors affecting the choice of first-line therapy in Parkinson's disease patients in Wales: A population-based study. Saudi Pharm J. 2021;29:206-212; doi: 10.1016/j.jsps.2021.01.004; Paik J. Levodopa inhalation powder: a review in Parkinson's disease. Drugs. 2020;80:821-828; Schrag, Anette et al. “Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson's disease: a cohort study.” The Lancet. Neurology vol. 16,1 (2017): 66-75. doi:10.1016/S1474-4422(16)30328-3.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Tan is on the Speakers’ Bureaus for Allergan, CSL Behring, Janssen, and Portola. Members of the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Tan was recorded at Parkinson’s Disease and Beyond: An Update of Movement Disorder, held October 24, 2020, and presented by Cedars Sinai Medical Center. For information about upcoming CME activities from Cedars Sinai Medical Center, visit cedars-sinai.edu. Audio Digest thanks the speakers and the meeting sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

FP700502

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

More Details - Certification & Accreditation