Early Management of Parkinson’s Disease

1. Early Management of Parkinson’s Disease Part 4 of 7

2. Early Management of PD • Provide symptomatic relief • Reduce functional disability • Reduce or delay long-term complications of drug therapy • motor fluctuations • dyskinesia • Slow disease progression: “neuroprotection” www.wemove.org

3. Clinical Decision-Making in Early PD • Disease severity • degree of functional impairment • impact on quality of life • Age of patient • comorbidities • risk of acute drug intolerance • risk of long-term complications www.wemove.org

4. When to Begin Therapy • Definitive neuroprotective therapy not yet available • Timing of symptomatic therapy is individual • degree of functional impairment • lifestyle of patient www.wemove.org

5. Potential Strategies for Neuroprotection • Selegiline (MAO-B inhibitor) • Anti-oxidants (vitamin C or E) • Co-enzyme Q • Dopamine agonists • Levodopa • Estrogen • NMDA receptor antagonists • Neurotrophic factors • Riluzole • Neuroimmunophilin ligands www.wemove.org

6. Initial Therapy: Patient Considerations • Risk of acute drug intolerance • Risk of long-term drug-related complications • Polypharmacy • Comorbidities, especially dementia • Patient’s lifestyle, responsibilities • Cost of medications • Functional vs. chronological age www.wemove.org

7. Initial Therapy: The Elderly Patient • Shorter treatment horizon • Lower risk of long-term complications • Higher likelihood of comorbidities • Levodopa: well tolerated, effective • Use adjunctive medications cautiously • Avoid sedating medications www.wemove.org

8. Initial Therapy: The Young Patient • Long-term treatment horizon • Increased risk of long-term complications • Increased patient responsibilities • Dopamine agonist monotherapy • Levodopa-sparing strategies • Putative neuroprotective strategies • Role of levodopa is not adequately defined www.wemove.org

9. Initial Therapy: What is the Chief Complaint? Predominant Symptom Clinical Options No functional impairment Delay therapy Mild symptoms Amantadine, selegiline Discrete symptoms Tremor—anticholinergic Depression—antidepressant Anxiety—anxiolytic Functionally disabling Levodopa, dopamine symptoms agonist, COMT inhibitor www.wemove.org

10. Levodopa: Guidelines in Early PD • Start low and increase slowly • Titrate dosage to efficacy (~200-600 mg/day) • Immediate release • more rapid onset • shorter duration of benefit • generic available • Controlled release • longer duration of benefit • some patients prefer less frequent dosing • Acute side effects: nausea, dizziness, somnolence www.wemove.org

11. Dopamine Agonists: Guidelines in Early PD • Effective as monotherapy • Less symptomatic benefit than levodopa • May delay need for levodopa approx. 12 months • data up to >3 years has been presented • Start low and increase slowly • Titrate to efficacy • bromocriptine 7.5-30 mg/day • pergolide 1.5-4.5 mg/day • pramipexole 1.5-4.5 mg/day • ropinirole 3-24 mg/day • Acute SEs: nausea, dizziness, somnolence, confusion www.wemove.org

12. Dopamine Agonists:Adjunctive Use with L-dopa • Bromocriptine, pergolide, pramipexole, ropinirole • Agonist choice is more art than science • Reduce levodopa dosage when adding the agonist • Failure of one does not predict failure of another • Agonists may be switched either gradually or rapidly to a comparable dosage www.wemove.org

13. Managing Early Complications: Wearing Off/Mild Dyskinesia • For pts on DA monotherapy: • elevate dosage of agonist • add LD, w/ or w/o COMT inhibitor • For pts on LD: • add DA, COMT inhibitor, or MAO inhibitor • reduce LD dosage • use combination of immediate and CR www.wemove.org

14. Managing Early Complications: Altered Mental States • Confusion, sedation, dizziness, hallucinations, delusions • Reduce or eliminate CNS-active drugs of lesser priority • anticholinergics – sedatives • amantadine – muscle relaxants • hypnotics – urinary spasmodics • Reduce dosage of DA, COMT inhibitor, or LD www.wemove.org

15. Faculty for the WE MOVE Parkinson’s Disease Teaching Slide Set Mark Stacy, MD Barrow Neurological Institute Phoenix, Arizona, USA Charles H. Adler, MD, PhD Mayo Clinic Scottsdale Scottsdale, Arizona, USA Kathleen Albany, PT, MPH WE MOVE New York, New York, USA Richard B. Dewey, Jr., MD University of Texas Southwestern Medical Center Dallas, Texas, USA William G. Ondo, MD Baylor College of Medicine Houston, Texas, USA Rajesh Pahwa, MD University of Kansas Medical Center Kansas City, Kansas, USA Ali H. Rajput, MD Royal University Hospital Saskatoon, Saskatchewan, Canada Lisa M. Shulman, MD Health Policy Fellow U.S. House of Representatives Washington, DC, USA Celia Stewart, PhD Mount Sinai Medical Center New York, New York, USA Reviewed by the Education Committee of the Movement Disorder Society www.wemove.org