Medication Management & Strategies When the levodopa honeymoon is over Eric J Pappert, MD Parkinson s Disease & Movement Disorders Center Neurology Associates
Medication Options in Parkinson s Carbidopa/Levodopa Dopamine agonists COMT-inhibitors MAO-B Inhibitors Antiviral agents (amantadine) Anticholinergic medications
Carbidopa/Levodopa Treats symptoms of: Stiffness / rigidity Tremor Slowness of movement Walking problems Carbidopa reduces nausea and vomiting Examples: Sinemet, Sinemet CR, Rytary, Duopa, Parcopa
Carbidopa/Levodopa Advantages: Most effective agent in treating symptoms Robust response Long history of use Relatively rapid absorption Well tolerated in many people
Carbidopa/Levodopa Limitations: Short half-life Pulsatile stimulation of dopamine receptors Does not treat all features of PD Freezing, postural instability, autonomic dysfunction, speech abnormalities, dementia Eventual diminished response
Carbidopa/Levodopa Limitations: Reduced conversion as disease progresses Does not stop disease progression Emergence of complications Motor fluctuations, dyskinesias (involuntary movements caused by medication)
Motor Fluctuations Predictable: Wearing Off Return of Parkinsonian signs or symptoms Cramping / spasm Off Dystonia Sensory / Behavioral / Autonomic Off Pain, restlessness Depression, anxiety, panic attacks Sweating, bloating, trouble breathing
Response to Levodopa and Disease Olanow CW, Agid Y. Available at: http://www.medscape.com/viewprogram/1847 Progression On/Off Early Moderate Advanced Clinical Effect Clinical Effect Clinical Effect Time (h) 0 2 4 6 Long duration of motor response Low incidence of dyskinesias 0 2 4 6 Shorter duration of motor Very short duration of motor ON response ON response Increased incidence of ON time consistently dyskinesias associated with dyskinesias 0 2 4 6
Motor Fluctuations Unpredictable: Delayed On periods, dose failures Sudden Off periods Super Offs Weak response at end of day
Strategies for Wearing Off Smaller doses of Levodopa less frequently Low protein diet Take Levodopa 90 mins before meals Consider change in medications: Long-acting Levodopa (Sinemet CR ) Dopamine agonists or MAO-B inhibitors Continuous dopamine infusion (Duopa ) The Victory Summit San Antonio, TX November 14, 2015 2015 Davis Phinney Foundation
The Classics: Therapies for Motor Fluctuations Levodopa/Carbidopa MAO-B Inhibitors Rasagiline/Azilect Selegiline/Eldepryl Ropinirole/Requip Pramipexole/Mirapex Rotigotine/Neupro Apomorphine/Apokyn injection Trihexyphenidyl Benztropine Entacapone/Comtan Tolcopone/Tasmar
Dopamine Agonists Advantages: Mimic the effect of dopamine Longer-lasting effect than Levodopa Effective single therapy (early Parkinson s) Reduced Levodopa-related motor complications Examples: Parlodel, Requip, Mirapex, Neupro, Apokyn
Dopamine Agonists Disadvantages: Side effects Does not completely prevent Levodopa-related motor complications Additional dopaminergic therapy needed as disease progresses Does not treat all features of PD (freezing, postural instability, autonomic dysfunction, dementia)
COMT Inhibitors Advantages Extends duration of Levodopa effect By inhibiting enzyme COMT Addition to Caribdopa/Levodopa for individuals experiencing wearing off effect No role as single therapy used only in combination with Levodopa Examples: Coman, Tasmar, Stalevo
Common Side Effects of Medications Light-headedness Dry mouth Confusion Nightmares Dyskinesias Drowsiness
Less Common Side Effects of Medications Impulse control disorders Sleep attacks Leg swelling
Deep Brain Stimulation: Chronic (high-frequency) Electrical Stimulation Via Electrodes Connected by a Subcutaneous Wire Implantable Pulse Generator: Many Current Configurations
The Newcomers: Therapies for Motor Fluctuations Levodopa/carbidopa IR & CR (Rytary TM ) Levodopa/carbidopa /carbidopa infusion (Duopa )
The Future: Therapies for Motor Fluctuations #1 Orafuse levodopa/carbidopa /carbidopa #2 Inhaled levodopa/carbidopa #3 Melevodopa- Liquid LD/CD #4 Levodopa/carbidopa infusion MAO-B Inhibitors Safinamide Amantadine ER Opicapone #1 Inhaled Apomorphine #2 Apomorphine infusion #3 Sublingual Apomorphine
The Future: Treatments for Dyskinesias Adenosine A2A Inhibitors: Tozadent Glutamate Antagonists: Mavoglurant Serotonergic Agonists: Eltoprazine
Medication Action Items Or Tenets To Live By
Tenet #1 You must properly grieve the loss of part of your health and accept this as part of you 1. Denial 2. Anger 3. Bargaining 4. Depression 5. Acceptance
Tenet #2 You must accept your portion of responsibility for your well-being General health & diet Avoiding harm & vanity: using walker Exercise your body & mind: Physical / speech / occupational therapies Home exercise program / POPS
Tenet #3 Be an effective communicator with MD & team When do you wake up / sleep / eat meals? List of your medications & times of day What has changed & when does it occur? What can t you do that you must do or want to do? Non-motor complaints: Memory / anxiety / sadness
Tenet #4 Focus on the positive: All that remains good Have a purpose Don t allow PD to be who you are
Questions: Can you tell us if there are any new medication treatments in the pipeline for Parkinson s? What is dystonia? Is it a disease, or just a symptom? Is there anything I can do to slow down the progression of the disease?
Questions: I ve been told that exercise is important. How truly important is exercise to a person with Parkinson s? Is it true that taking Levodopa earlier in PD decreases the medication s long term usefulness? Does this apply to higher doses also?
Questions: I can t move at all sometimes. What is the cause, and what should I do about it? Do all people with Parkinson s eventually have dementia? How severe will my cognitive problems become?
Questions: Additional questions
Thank You Eric J. Pappert, MD Parkinson s Disease & Movement Disorders Center, Neurology Associates San Antonio, TX