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Parkinson’s Disease Foundation

PD ExpertBriefing: Maximizing PD : How to Get the Most Out of Your Treatment Plan

Led By: Connie Marras, M.D., Ph.D., Associate Professor of Neurology, University of Toronto, Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, Canada

To hear the session live on: Tuesday, April 28, 2015 at 1:00 PM ET.

DIAL: 1 (888) 272-8710 and enter the passcode 6323567#.

View the session live on the computer by visiting: http://event.netbriefings.com/event/pdeb/Live/medications2/

If you have any questions, please contact: Valerie Holt at [email protected] or call (212) 923-4700

1

Introduction

James Beck, Ph.D. Vice President, Scientific Affairs Parkinson’s Disease Foundation

2 Maximizing Medications: How to Get the Most Out of Your Treatment Plan

Connie Marras M.D., Ph.D. Associate Professor, University of Toronto Morton and Gloria Shulman Movement Disorders Centre Edmond J Safra Program in Parkinson’s disease Toronto Western Hospital

3 Objectives

• Review the classes of for Parkinson’s disease. • Learn about what effects (good and bad) can be expected from PD medications. • Understand ways to maximize the effectiveness of PD medications and minimize side effects.

4 Classes of Medication for Motor Symptoms in PD • Levodopa medications • • B (MAO-B) inhibitors • -O-Methyl Transferase (COMT) inhibitors •

5 Classes of Medication for Motor Symptoms of PD • Levodopa – Levodopa/ (Sinemet, levocarb), levodopa/ (Prolopa), intestinal gel (Duodopa, Duopa)

6 Classes of Medication for Motor Symptoms of PD • Levodopa – Levodopa/carbidopa (Sinemet, levocarb), levodopa/benserazide (Prolopa), intestinal gel (Duodopa, Duopa) • Dopamine agonists – , , (patch), , , others

7 Classes of Medication for Motor Symptoms of PD • Levodopa – Levodopa/carbidopa (Sinemet, levocarb), levodopa/benserazide (Prolopa), intestinal gel (Duodopa, Duopa) • Dopamine agonists – Pramipexole, ropinirole, rotigotine (patch), cabergoline, apomorphine, others • (MAO-B) inhibitors – ,

8 Classes of Medication for Motor Symptoms of PD • Levodopa – Levodopa/carbidopa (Sinemet, levocarb), levodopa/benserazide (Prolopa), intestinal gel (Duodopa, Duopa) • Dopamine agonists – Pramipexole, ropinirole, rotigotine (patch), cabergoline, apomorphine, others • Monoamine oxidase B (MAO-B) inhibitors – Selegiline, rasagiline • Catechol-O-Methyl Transferase (COMT) inhibitors – ,

9 Classes of Medication for Motor Symptoms of PD • Levodopa – Levodopa/carbidopa (Sinemet, levocarb), levodopa/benserazide (Prolopa), intestinal gel (Duodopa, Duopa) • Dopamine agonists – Pramipexole, ropinirole, rotigotine (patch), cabergoline, apomorphine, others • Monoamine oxidase B (MAO-B) inhibitors – Selegiline, rasagiline • Catechol-O-Methyl Transferase (COMT) inhibitors – Entacapone, tolcapone • Anticholinergics – , cogentin, ethopropazine, others

10 Classes of Medication for Non- Motor Symptoms in PD • • Bladder antispasmodics for urinary urgency • inhibitors for cognitive impairment • Remedies for • …

11 How Do They Work?

• Dopaminergic medications

– Levodopa Dopamine

12 How Do They Work? COMT inhibitors (entacapone, tolcapone)

levodopa levodopa

COMT Inhibitor dopamine

dopamine

13 How Do They Work?

• Dopaminergic medications

– Levodopa Dopamine – COMT inhibitor: action of levodopa

14 How Do They Work?

• Dopaminergic medications

– Levodopa Dopamine – COMT inhibitor: action of levodopa

– Dopamine • Mimics dopamine at dopamine receptors

15 How Do They Work?

• Rasagiline, selegiline – Reduce breakdown of dopamine

• Anticholinergics – Reduce activity of acetylcholine

16 How Are They Used?

• Levodopa – Cornerstone of treatment – Usually initial medication in patients >60 – Often initial medication in younger patients – Most effective medication for Parkinson’s disease – Often least side effects

17 How Are They Used?

• Dopamine agonists (ropinirole, pramipexole, cabergoline…) • MAO-B inhibitors (selegiline, rasagiline)

– Longer acting than levodopa – May be used alone as initial treatment in younger patients – Often used in combination with levodopa to smooth out wearing off

18 How Are They Used?

• COMT inhibitors (entacapone, tolcapone) – Used in conjunction with levodopa – Increases duration of action of levodopa – Used to reduce end of dose wearing off

19 How Are They Used?

• Anticholinergics (trihexyphenidyl, others) – Used to treat tremor preferentially

• – Used primarily to reduce

20 What Benefits to Expect from Your Medications 1. Better speed of movement 2. Better dexterity 3. Less stiffness 4. Less tremor (most but not all patients) 5. Also possible: • Clearer thinking • Less pain • Better balance (esp. early on)

21 Problems Encountered with Medications • (levodopa, dopamine agonists)

22 Problems Encountered with Medications • Nausea (levodopa, dopamine agonists) • Sleepiness (levodopa, dopamine agonists)

23 Problems Encountered with Medications • Nausea (levodopa, dopamine agonists) • Sleepiness (levodopa, dopamine agonists) • /Confusion (particularly older patients) (anticholinergics, amantadine, MAO-B inhibitors, dopamine agonists)

24 Problems Encountered with Medications • Nausea (levodopa, dopamine agonists) • Sleepiness (levodopa, dopamine agonists) • Hallucinations/Confusion (particularly older patients) (anticholinergics, amantadine, MAO-B inhibitors, dopamine agonists) • Lightheadedness (levodopa, dopamine agonists, amantadine)

25 Problems Encountered with Medications • Nausea (levodopa, dopamine agonists) • Sleepiness (levodopa, dopamine agonists) • Hallucinations/Confusion (particularly older patients) (anticholinergics, amantadine, MAO-B inhibitors, dopamine agonists) • Lightheadedness (levodopa, dopamine agonists, amantadine) • Constipation (levodopa, anticholinergics)

26 Problems Encountered with Medications

• Nausea (levodopa, dopamine agonists) • Sleepiness (levodopa, dopamine agonists) • Hallucinations/Confusion (particularly older patients) (anticholinergics, amantadine, MAO-B inhibitors, dopamine agonists) • Lightheadedness (levodopa, dopamine agonists, amantadine) • Constipation (levodopa, anticholinergics) • Dyskinesias (levodopa, dopamine agonists)

27 Wearing off and Dyskinesias

28 Maximizing Benefits

• Dose • Timing • • Constipation • Stomach emptying • Mood

29 Maximizing Benefits

Dose • Wide range, particularly with levodopa • Increase dose gradually until sufficient benefit • Reduce when adverse effects appear • Do not stop suddenly! Dose Dose

Years 30 Maximizing Benefits

• Timing (levodopa, dopamine agonists) – Early on rarely matters – Later can be very important Levodopa Levodopa

dose dose dose

Hours

31 Maximizing Benefits

Dyskinesia Levodopa Levodopa

Wearing off dose dose dose (tremor, slowness) Hours

32 Patient Diary

33 End of Dose Wearing Off • Reduce interval between doses • Levocarb CR (controlled release) • Add • Add COMT inhibitor • Add selegiline • Liquid Sinemet • Advanced therapies (levodopa/carbidopa intestinal gel, deep brain stimulation)

34 Food

• Protein competes with levodopa for transport from gut to blood and into brain • Can result in sudden OFF periods or delayed ON • Avoiding protein 30 minutes before and one hour after medication may improve effect – Meat, fish, eggs, dairy • Medication on empty stomach may be even better

35 Constipation

• Is a symptom of Parkinson’s disease • Can be made worse by PD medications • Reduces absorption of medication • Tips: – Drink plenty of water – Exercise – Take daily laxative for prevention if necessary

36 Slow Stomach Emptying

• Delayed emptying of the stomach is a symptom of Parkinson’s disease • Delays onset of action of levodopa • Causes bloating, reflux • Tips: – (not available in US)

37 Mood

• and anxiety are common symptoms of PD • Depression and anxiety commonly precede motor symptoms • Mood has a profound effect on of medication

38 Minimizing Adverse Effects

• Nausea – Take medication with food (non-protein if necessary) • E.g. bread, crackers, apple sauce, other fruit – Domperidone, other antinauseant medications

39 Minimizing Adverse Effects

• Lightheadedness on standing – Drink plenty of water – Take extra salt – Compression stockings – Elevate head of bed – Reduce dose of levodopa, dopamine agonist, amantadine – Domperidone, extra carbidopa – Medications to raise : , fludrocortisone

40 41 42 43 Dyskinesias

1. Peak Dose Dyskinesias At best effect of levodopa/dopamine agonist

Levodopa

Hours

44 Dyskinesias

1. Peak Dose Dyskinesias At best effect of levodopa/dopamine agonist

Levodopa

Hours

Reduce peak action of medication 45 Peak Dose Dyskinesias: Treatment • Reduce dose of medication (number of tablets with each dose) • Amantadine • Advanced therapies (duodopa, deep brain stimulation)

46 Dyskinesias 2. Diphasic dyskinesias With wearing off and start of effect

Levodopa

Hours

47 Dyskinesias 2. Diphasic dyskinesias With wearing off and start of effect

Levodopa

Hours

Reduce wearing off

48 Diphasic Dyskinesias (Dyskinesias with Wearing Off): Treatment

• Reduce wearing off: • Take medication more frequently • Lengthen duration of action of levodopa – Sinemet CR – COMT inhibitor • Adjunctive medication for wearing off (MAO-B inhibitor, dopamine agonist) • Advance therapies (levodopa/carbidopa intestinal gel, deep brain stimulation)

49 Hallucinations/Confusion

• Reduce medications • Remove 1. Anticholinergics 2. Amantadine 3. COMT inhibitor 4. MAO-B inhibitor • Reduce levodopa • medications (, )

50 Sleepiness

• Reduce dose of medication • Minimize dopamine agonist • Medications to promote wakefulness (e.g. )

51 Impulse Control Disorders

• Compulsive – Gambling – Shopping – Eating – • Associated with dopamine agonists, levodopa

52 Impulse Control Disorders: Management

Early detection: have partner, family look out for concerning behaviours Prevent loss: prevent access to cash if necessary Treatment: Reduce/discontinue dopamine agonist

53 Key tips

• Don’t delay treatment at the expense of quality of life • Treatment of depression and anxiety are critical to good effect of medication • Timing of benefits and adverse effects in relation to dose are often key to optimizing benefit • PD does not change suddenly! Look for other causes: – Constipation – Infection (, ) – Other medical illness

54 Thank You!

“Just like the Tin Man in the Wizard of Oz, I need my oil can to live with Parkinson's disease. The pillbox depicted in my digital photograph is much like that oil can; it keeps me moving day by day.”

“Day by Day” by Wendell Lowe, PDF Creativity Artist

55 Questions and Discussion

56 Resources from PDF

Fact Sheets PD Resource List •Understanding •750 resources in the Parkinson’s Parkinson’s Medicaons community

Parkinson’s HelpLine •Available at (800) 457-6676 or [email protected] •Monday through Friday •9:00 AM – 5:00 PM ET

57 Upcoming PD ExpertBriefings

Challenges of Advanced PD and Tips for Better Living Tuesday, June 23, 1:00 PM - 2:00 PM ET Peter Fletcher, M.B.Ch.B., M.Sc., Consultant Physician, Department of Old Age , Gloucestershire Hospitals NHS Foundation Trust, United Kingdom

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