Parkinson's Disease Management

See Also

Management

Consult neurology
1. Especially for all patients with onset under age 60 years
Adjunctive services
1. Group support
2. Disease specific education
3. Nutrition guidance (Healthy Diet)
4. Avoid Herbals and supplements to treat Parkinsonism
  1. No evidence of benefit (including Vitamin E)
Exercise guidance (consider physical therapy Consultation)
1. Stretching
2. Strengthening
3. Balance training
4. Voice training
Medications
1. See Levodopa
2. See Dopamine Agonist
3. See treatment algorithm below
4. See adjunctive managament below
Surgical management
1. See Thalamic Stimulation (Deep Brain Stimulation)

Management
Treatment Algorithm

Precautions
1. Levodopa is the most effective agent, but has serious Extrapyramidal Side Effects
2. Longterm Levodopa causes Dyskinesias that may be permanent
3. Delay starting Levodopa until it is indicated (see protocol below)
  1. However, start when there is any impact on activity
No functional deficit (normal ADLs, quality of life)
1. No medications needed
2. See General Measures below
Cognitive Changes and Functional Disability
1. Conservative use of Sinemet
No Cognitive changes
1. No functional Disability
  1. Consider Selegiline (Eldepryl)
2. Mild Functional Disability with Tremor predominant
  1. Consider Amantadine
  2. Consider Anticholinergics
    1. Trihexyphenidyl HCl (Artane)
    2. Benztropine mesylate (Cogentin)
3. Moderate to severe functional Disability
  1. Carbidopa/Levodopa (Sinemet SR)
  2. Consider Dopamine Agonists (see below)
Late Stage Parkinson's Disease
1. Characteristics
  1. Dyskinesia (involuntary Choreiform movements)
  2. Early wearing-off effect of Levodopa (off-time)
  3. On-Off fluctuations in motor activity
2. Medication Adjuncts (used in Consultation with Neurology for off-time symptoms)
  1. Inbrija (inhaled Levodopa)
    1. Rapid onset (10 min after inhalation) and duration of 1 hour used for prn "off time" rigidity or Tremor
    2. Less expensive ($30/dose) than Apokyn ($200/dose), an injectable option for off-time
    3. Requires dexterity to replace capsule in Inhaler
    4. Avoid in underlying lung disease (e.g. Asthma, COPD) due to bronchospasm risk
    5. (2019) Presc Lett 26(5)
  2. Non-ergot Dopamine Agonists (preferred, most effective agents at reducing off-time)
    1. Pramipexole (Mirapex)
    2. Ropinirole (Requip)
    3. Apomorphine (Apokyn) SQ Injection (Dopamine Agonist prn for off-time)
  3. COMT Inhibitors
    1. Entacapone (Comtan)
  4. MAO-B Inhibitors
    1. Selegiline HCL (Eldepryl) 5 mg at breakfast and lunch
      1. Available generically for $90/month
      2. Contrast with Rasagaline for $430, Safinamide for $670
    2. Rasagiline (Azilect) 0.5 mg orally daily (may be increased to 1 mg orally daily)
    3. Safinamide (Xadago) 50 mg orally daily (may be increased to 100 mg orally daily)
  5. Amantadine
3. Surgery
  1. Deep Brain Stimulation

Management
Adjunctive Medications

Monoamine oxidase Type B inhibitor
1. General
  1. Less effective than Sinemet or Dopamine Agonists
  2. Fewer adverse effects including less diskinesia
2. Preparations
  1. Selegiline HCL (Eldepryl) 5 mg at breakfast and lunch (generic for $90 per month)
  2. Rasagiline (Azilect) 0.5 mg orally daily (may be increased to 1 mg orally daily)
  3. Safinamide (Xadago) 50 mg orally daily (may be increased to 100 mg orally daily)
Anticholinergic Medications
1. Preparations
  1. Trihexyphenidyl HCl (Artane)
    1. Artane 4-10 mg/day divided tid
  2. Benztropine mesylate (Cogentin)
    1. Cogentin 1-4 mg/day divided qd-bid
2. Adverse effects (limit use to under age 70)
  1. Memory Impairment
  2. Hallucinations
  3. Dry Mouth
  4. Urinary difficulty
  5. Blurred Vision
Adjunctive Agents (Vitamin Supplementation)
1. Amantadine HCL (Symadine, Symmetrel)
  1. Decreases Levodopa induced motor disorder (only agent to reduce Dyskinesias)
    1. Dyskinesia reducing effect may be only modest and may last for less than 8 months
  2. Continue long-term
  3. Metman (1999) Arch Neurol 56:1383-6 [PubMed]
2. Conenzyme Q10 360-1200 mg PO daily
  1. Shults (2002) Arch Neurol 59:1541-50 [PubMed]
COMT Inhibitors
1. Indications
  1. Late-stage Parkinson's Disease
2. Mechanism
  1. Extends Levodopa half-life
3. Agents
  1. Entacapone (Comtan)
  2. Tolcapone (Tasmar) - avoid
    1. Rare lethal hepatotoxicity (closely watch Liver Function Tests)
Adenosine Antagonist
1. Istradefylline (Nourianz)
  1. Marketed as non-Dopaminergic adjunct for off-time symptoms (e.g. Tremor)
  2. However, efficacy is low, cost is high ($1500/month) and has adverse effects (e.g. Dyskinesias, Hallucinations)
  3. (2020) presc lett 27(2): 10-1

Management
Miscellaneous non-motor conditions

Constipation
1. Increase fluids and fiber
2. Wean Anticholinergics
3. Consider polyethylene gylcol (Miralax) and enemas as needed
Major Depression
Cognitive Impairment (Dementia)
1. Present in 60% of Parkinsonism patients by 12 years from Parkinsonism onset
2. Wean any Anticholinergics
3. Consider Cholinesterase Inhibitors (e.g. Aricept)
Dysphagia
1. Swallowing evaluation
2. Use adjuncts to extend medication active time
3. Eat during "on" time and stick to soft foods
Drooling
1. Glycopyrolate
2. Botox
Urine urgency
1. Consider Oxybutynin (Ditropan)
Psychosis or Hallucinations
1. Wean Anticholinergics, Dopamine Agonists (e.g. Amantadine, benztropine, selegeline)
2. Decrease Levodopa dosing
3. Consider low dose Antipsychotics
  1. Clozapine (Clozaril)
  2. Quetiapine (Seroquel) 12.5 mg daily
4. Avoid harmful agents
  1. Avoid Nuplazid (pimavanserin, Serotonin-selective agent) until further study
    1. Expensive with potential for serious adverse effects
    2. http://www.fiercebiotech.com/regulatory/updated-fda-s-internal-review-of-acadia-s-parkinson-s-drug-raises-safety-benefit
  2. Avoid Zyprexa
    1. Ineffective for Psychosis in Parkinsonism
    2. Exacerbates motor symptoms
  3. Avoid Haloperidol
    1. Exacerbates motor symptoms, and adverse effects may be severe
Fatigue (one-third of Parkinsonism patients)
1. Carbidopa-Levodopa is associated with less Fatigue
2. Methylphenidate (Ritalin) may improve Fatigue
Sleep disturbance
1. Daytime somniolence (>50% of Parkinsonism patients)
  1. Stop Dopamine Agonists
  2. Melatonin is NOT effective in Parkinsonism
  3. Modafinil (Provigil)
    1. Do not use to prevent sleep attacks
2. Sleep attacks
  1. Do not perform hazardous duties
  2. Do not drive
  3. Do not operate machinery
3. Awakens from Bradykinesia
  1. Sinemet before bed or
  2. COMT Inhibitor or
  3. Dopamine Agonist
4. REM Sleep Behavior Disorder
  1. Presents with dramatic and sometimes violent activity during sleep (yelling, kicking, jumping)
  2. Decrease nighttime anti-parkinson drug dose and
  3. Consider Clonazepam (Klonopin)
5. Restless Leg Syndrome
  1. See Restless Leg Syndrome for management

References

Ahlskog (2011) Mayo Internal Medicine Review Lecture
Schim (2001) CMEA Medicine Lecture, San Diego
Clarke (2003) Clin Evid 10:1582-98 [PubMed]
Clarke (2004) Lancet Neurol 3:466-74 [PubMed]
Gazewood (2013) Am Fam Physician 87(4): 267-73 [PubMed]
Nutt (2005) N Engl J Med 353:1021-7 [PubMed]
Olanow (2001) Neurology 56:S1-88 [PubMed]
Rao (2006) Am Fam Physician 74:2046-56 [PubMed]
Young (1999) Am Fam Physician 59(8):2155-67 [PubMed]