Treatment of Parkinson Disease

1. Treatment of Parkinson Disease David Tran, 2013 Mercer University PharmD Candidate

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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.

12. 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?

13. 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.