• Clinical science

Medication for Parkinson disease

Abstract

There are many pharmacologic options available for the treatment of Parkinson disease, and regimens are individualized depending on the patient's age, symptoms, and symptom severity. However, currently, only symptomatic treatment is possible, though drugs which may slow or reverse the course of the disease are currently being investigated. Since treatment of Parkinson disease at an early stage can significantly improve a patient's subjective well-being (honeymoon period), medical therapy should be initiated as soon as symptoms begin to interfere with the patient's daily life. For most patients, first-line treatment consists of levodopa (L-DOPA) or dopamine receptor agonists, such as ropinirole and pramipexole. Other drugs that are used to treat Parkinson disease include amantadine, MAO-B inhibitors, and COMT inhibitors.

Overview

Substance class Agent Mode of action Indication Additional information
Dopamine precursors
  • L-DOPA is converted to dopamine by DOPA decarboxylase at the presynaptic neurondirect dopaminergic effect (especially at D2 receptors)
  • Predominantly controls bradykinetic symptoms
  • First-line treatment for patients > 65 years of age or patients with comorbidities
    • Second-line treatment choice for refractory disease:
  • Second-line treatment for patients < 65 years of age
  • Mostly given as monotherapy in combination with decarboxylase inhibitors
  • Most effective drug for reducing symptoms
  • However, increased risk of severe motor dysfunction with long-term use (see “Side effects” below)
  • Administer between meals (e.g., 30 minutes before a meal) to increase gastrointestinal absorption (→ avoid high-protein diets)
Decarboxylase inhibitors
  • Always administered together with L-DOPA
Dopamine agonists Non-ergot
  • Act directly at striatal dopamine receptors
  • Predominantly control bradykinetic symptoms
  • First-line treatment for patients < 65 years of age
  • Less effective than L-DOPA, but fewer side effects
  • Effective in advanced disease stages
Ergot
  • Second-line treatment for patients < 70 years of age
COMT inhibitors
  • Inhibition of the peripheral (entacapone) or central (tolcapone) catechol-O-methyl transferase (COMT) → ↓ metabolization of dopaminedopamine effect↓ demand for L-DOPA and longer therapeutic effect for each dose
NMDA antagonists
  • Acts antagonistically at the glutamate N-methyl-D-aspartate (NMDA) receptor → dopaminergic effect
  • Mostly controls bradykinetic symptoms
  • Short-term treatment of mild symptoms
  • Drug of choice during akinetic crisis
  • Reduction of L-DOPA-induced dyskinesia
  • Loss of effect after several months of treatment → cannot be used for long-term therapy
  • May have cardiac side effects (prolonged QT interval)
MAO-B inhibitors
  • Inhibition of MAO-Bdecreased dopamine metabolization in the brain → prolonged dopamine effect → ↓ demand for L-DOPA
  • Alternative to L-DOPA or dopamine agonists for short-term therapy in patients with mild symptoms in early disease stages

Anticholinergic drugs
(muscarinic antagonists)

  • Useful as monotherapy in patients < 65 years with tremor as the main complaint
  • May be used as an adjunct if tremor is not sufficiently controllable with standard treatment

Patients who do not respond to levodopa therapy will not respond to dopamine agonist therapy!

References:[1][2][3][4][5]

Side effects

L-DOPA (in combination with carbidopa)

Dopamine agonists

Other substances

NMDA antagonist can cause prolonged QT intervals! Do not administer NMDA antagonists to patients with a history of cardiac disorders!

Administration of antimuscarinic drugs to patients with mental disorders or delirium will likely worsen psychiatric symptoms!

References:[6][7]

We list the most important adverse effects. The selection is not exhaustive.

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last updated 12/03/2018
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