Treatment of Parkinson Disease

David Tran, 2013 Mercer University PharmD Candidate

Epidemiology

Second to Alzheimer disease as the most common neurodegenerative disorder

Men affected more than women Peak onset between 55 and 65 years Occurs in 1% to 2% of individuals older than 60

years Estimated prevalence is 1 million individuals in the

U.S. and 5 million individuals worldwide Positive risk factors- advanced age, family history of

Parkinson disease, early-life rural living, early exposure to pesticides and heavy metals

Protective risk factors- cigarette smoking and caffeine use

Clinical Presentation

4 cardinal manifestations- resting tremor, bradykinesia, rigidity, and gait disturbance

Non-motor symptoms- dementia, depression, anxiety, sleep disturbance, and autonomic dysfunction

Typically presents with unilateral or asymmetric motor signs

Medical Treatment

Levodopa (grade A) Peripheral decarboxylase inhibitors Dopamine agonists (grade B) Catechol-o-methyl transferase inhibitors (grade

B) Monoamine oxidase B inhibitors (grade C) Anticholinergics (grade C) Amantadine (grade B and C) Deep brain stimulation

Medical Treatment of Advanced Parkinson Disease 30-50% of patients develop motor

complications within 5 years of treatment with Levodopa

Duration of response to each dose shortens Dyskinesia as a result of excessive Levodopa Dystonia due to wearing-off effects of

Levodopa

Management of Motor Fluctuations Levodopa adjustments

Dystonia and wearing-off effects reduce Levodopa dose intervals

Dyskinesia reduce Levodopa dose No response to Levodopa increase dose or reduce

dose interval Enzyme inhibitors

COMT and MAO-B inhibitors Prolong and potentiate Levodopa effects

Dopamine agonists

Deep Brain Stimulation (DBS) Implantation of a stimulating electrode with 4 electrical

contacts into a brain target connected to a pulse generator

Improves bradykinesia, rigidity, and tremor while producing reversible effects without destroying significant amounts of brain tissue

Provides continuous relief from motor fluctuations 5% of patients with Parkinson disease severe enough to

warrant DBS use 60,000 DBS implants placed worldwide for Parkinson

disease

Effectiveness of Subthalamic DBS 3 prospective, randomized controlled trials

were conducted showed improvements in motor scores, daily

living scores while off medication, and quality of life scores

Levodopa dyskinesias improved, off-time was reduced, and on-time was increased

Level AIIa recommendation

Potential Complications of DBS Procedure-related

Foreign body reaction, surgical site infection, surgical site pain, cerebral hemorrhage

Hardware-related Paresthesias, dyskinesias, and muscle contractions

during programming, infection Adverse effects

Impaired verbal fluency, declines in working memory, processing speed, and delayed recall, acute depression, mania, aggressive behavior, increased suicide risk

Indications and Contraindications for DBS for Parkinson Disease Indications

Idiopathic Parkinson disease Disturbing motor fluctuations and/or dyskinesias unresponsive to medical

management Motor symptoms must be responsive to Levodopa Medication resistant tremor

Contraindications Atypical parkinsonism No response to Levodopa Main disability is gait freezing and postural instability Significant cognitive deficits Significant psychiatric disturbance Poor medical health Advanced age

Case Study

ML is a 64 y/o AAM with a past history of stroke who has advanced Parkinson disease. He was diagnosed with PD in 1999. He initially presented with left-sided clumsiness, loss of dexterity, and depression. Over the years, his symptoms progressed and has had increasing difficulty with fluctuating on/off symptoms. His current medication regimen is Carbidopa-Levodopa-Entacapone 31.25-125-200 mg q4h and Pramipexole 1 mg q4h. On this regimen, he has difficulty with fine and gross motor skills. Walking has slowed considerably with frequent episodes of gait freezing. His tremor is minor and intermittent. His voice has become softer and harder to understand. He reports feeling depressed and anxious due to his public perception. Pmh include left thalamic infarct in 1991 without residual symptoms and BPH. Other medications include Clonazepam 0.5 prn, Lansoprazole 30 mg daily, and Aspirin 81 mg daily.

Case Study

ML is experiencing moderate rigidity and severe bradykinesia of the upper extremities four hours after his last Levodopa dose. He walks with a stooped posture with decreased stride length and foot elevation. Forty-five minutes after his Levodopa dose, he developed dyskinesia of the head and upper extremities.

What treatment options are available to improve ML’s Parkinson disease management?

References

Jann, Michael. Neurodegenerative Disorders: Parkinson Disease. 12/12/2010

Tarsy, Daniel. Treatment of Parkinson Disease: A 64-Year-Old Man with Motor Complications of Advanced Parkinson Disease. JAMA. June 6, 2012:307(21);2305-2314.