Initial Treatment in Parkinson Disease

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Initial Treatment in Parkinson Disease

• Journal Club
• January 23, 2002
• Megan Mahoney

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Parkinson Disease A Primary Care Problem

• There are more than 1 million persons in the
  United States with PD
• More than 50 of patients with PD are treated by
  their PCP
• The general health of patient with PD is our
  responsibility after referral to specialist.

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Case Presentation

• LW, a 89 yo female ex-nurse assistant, is a new
  patient in clinic. Her daughter, who is her
  primary caregiver, reports worsening loss of
  balance and decreased facial expression
  beginning approximately 9 months ago. On ROS, pt
  endorses constipation and fragmented sleep. In
  general, the patient is an elderly African
  American women well-groomed with masked facies
  and expression-less, muffled speech. On exam,
  mild hand tremor at rest is present bilaterally.
  Profound bradykinesia is present, along with
  muscular rigidity bilaterally. Sensory exam is
  normal.

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Cardinal features of Parkinson Disease

• Tremor
• Akinesia or bradykinesia
• Rigidity
• Postural instability

• Possible PD
• 1 of the first three listed
• Probable PD
• 2 of the four listed
• (or 1 of first three if asymmetric)
• Definite PD
• 3 of the four listed

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Associated features of PD

• Motor
• Hypophonia
• Dysphagia
• Shuffling gait
• Masked facies
• Sensory
• Pain
• Paresthesia

• Autonomic dysfunction
• Constipation
• Urinary dysfunction
• Thermal dysregulation
• Seborrhea
• Psychiatric manifestations
• Sleep disturbances

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Therapeutic options for PD

• The motor symptoms of idiopathic PD are primarily
  the result of a progressive loss of
  dopamine-containing neurons in the substantia
  nigra. The midbrain above shows the normal
  pigmentation of the substantia nigra. The lack of
  pigmentation, seen below, is from a person with
  Parkinson disease.

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Levodopa

• Side Effects
• Nausea/Vomiting
• Orthostatic hypotension
• Psychological side effects
• Wearing off periods
• Dyskinesias

• Precursor to dopamine
• Crosses BBB
• Combine with Carbidopa to block peripheral
  conversion

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Dopamine Receptor Agonists

• Side effects
• Orthostatic hypotension
• Hypersomnolence
• Hallucinations
• Nausea/Vomiting

• Adjunctive medication to reduce dyskinesias
  secondary to levodopa
• Bromocriptine, Pergolide, Pramipexole, Ropinirole

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Other Anti-PD Therapies

• Anticholinergics particularly effective in
  reducing tremor, rigidity, drooling not in
  bradykinesias
• Amantindine not as effective as levodopa, can
  reduce severity of dyskinesias
• MAO-B inhibitors symptomatic benefit
• COMT inhibitors potentiates levodopa
• Vitamin E, Coenzyme Q10, evening primrose
• Physical Therapy, Exercise, Nutrition

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A Five-year Study of the Incidence of Dyskinesia
in Patients with Early Parkinsons Disease who
were Treated with Ropinirole or Levodopa
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How was randomization done?

• Participants were randomized 21 ropinirole vs.
  levodopa.
• Average age was 63 for both groups.
• Duration of disease, severity of disease,
  baseline ADLs and motor function scores were
  similar between the two groups.

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Was the study blinded?

• Both clinicians and patients were unaware of
  treatment arm assignment.
• Both groups were offered supplemental levodopa in
  an open label fashion.
• There was no follow-up assessment of blinding
  after completion of study.

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Was follow-up of patients long enough to capture
effect?

• Approximately 50 of patients with PD develop
  dyskinesias after 3 to 5 yrs of levodopa therapy.
• Intention-to-treat model was used to record
  incidence of dyskinesia, but not for other
  parameters.

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Are the results valid?
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Are the results valid?

• Reduced incidence of dyskinesias (hazard ratio
  2.82, 95 CI, Plt0.001)
• Length of time until dyskinesia in 25 of group
  was 214 wks in ropinirole vs. 104 wks in
  levodopa.

• At end of study, 20 of ropinorole group
  developed dyskinesias vs. 45 of levodopa group.
• Only 8 of ropinole group reported disabling
  dyskinesias vs. 23 of levodopa group.

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Are the valid results of this study important?

• Dyskinesia was recorded when patients had a score
  1 or more on 0-4 scale.
• Dyskinesia was reported as incidence, not
  severity.
• Incidence of disabling dyskinesia provides more
  information regarding severity.
• There was no measure done on quality of life.

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How does the harm of therapy compare to benefit?

• There was a slight worsening from baseline in the
  score for ADLs in ropinirole group, which was not
  significant. In levodopa group, there was no
  change in ADLs.
• The increment of improvement in motor function
  seen in two groups was significantly higher in
  levodopa group.

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How does the harm of therapy compare to benefit?

• Hallucinations were significantly increased in
  ropinirole group with NNH of 8 (compared to NNT
  of 4).
• Many patients prefer moderate dyskinesias to
  bradykinesias and rigidity.
• Cost is prohibitive.

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Bottom Line

• There is evidence to support that initial
  treatment with dopamine agonists delays the onset
  of dyskinesias, but may be less effective in
  treating motor function.
• Is the delay in complications worth the cost?
• Dopamine agonists should be avoided in patients
  prone to hallucinations and confusion, such as
  the elderly.