Medication for Parkinson disease

There are many pharmacologic options available for the treatment of Parkinson disease; regimens are tailored to the patient's age, symptoms, and symptom severity. While only symptomatic treatment is available at this point in time, drugs that 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, e.g., ropinirole and pramipexole. Other drugs that are used to treat Parkinson disease include amantadine, MAO-B inhibitors, and COMT inhibitors.

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

Selegiline has high selectivity for the monoamine oxidase B found predominantly in the brain.

To remember that anticholinergics like benztropine and trihexyphenidyl are used in the treatment of Parkinson disease, think of “A Benz for a trip to the park.”

To remember the main drugs used to treat Parkinson disease, think of A² B² C² D²: Antimuscarinics and Amantadine; Bromocriptine and MAO-B inhibitors; COMT inhibitors and Carbidopa; L-DOPA and nonergot Dopamine agonists.

References:^{[1][2][3][4][5]}

Carbidopa-levodopa

• Becomes less effective over time: may require a shorter interval between doses
• Autonomic symptoms
  • Nausea and vomiting
  • Orthostatic hypotension
  • Carbidopa reduces the risk of orthostatic hypotension, nausea, and vomiting.
• Psychiatric symptoms ^[6][7]
  • Hallucinations (often visual); and other psychotic symptoms → treat with clozapine
  • Anxiety, insomnia, agitation, and aggressive behavior
  • Increased risk in elderly patients, women, concurrent dementia or other psychiatric disorders (e.g., depression), long duration of levodopa treatment, and high doses
• Motor fluctuations
  • Hypokinesia
    • End-of-dose akinesia/wearing-off phenomenon
    • Freezing
    • On-off phenomenon; : Phases of good mobility (“on” phases) alternate with phases of poor mobility (“off” phases) as a result of reduced reaction to L-DOPA or wearing off of medication.
  • Dyskinesia (hyperkinesia)
    • On-period dystonia
    • Off-period dystonia
    • Diphasic dyskinesias
• Increased intraocular pressure
  • Open-angle glaucoma: Levodopa (and anticholinergics) should be used with caution.
  • Closed-angle glaucoma: Levodopa (and anticholinergics) are not recommended.
• Akinetic crisis
  • Definition: condition caused by severe dopamine deficiency (e.g., after discontinuation of L-DOPA therapy or insufficient L-DOPA absorption)
  • Clinical features: complete inability to move , incomprehensible speech, possibly hyperthermia → increased risk of dehydration, deep-vein thrombosis, and pneumonia
  • Treatment: intensive medical care, volume substitution, administration of L-DOPA, apomorphine, amantadine

Dopamine agonists

Side effects common to all dopamine agonists

• Autonomic
  • Nausea, vomiting
  • Orthostatic hypotension, dizziness
  • Increased daytime drowsiness, sleep attacks
• Motor function: dyskinesia (rare)
• Psychiatric ^[6][7]
  • Hallucinations, psychosis
  • Impulse control disorders
    • Manifestations: e.g., pathological gambling, hypersexuality, compulsive shopping
    • Management: dose reduction or discontinuation until symptoms resolve
  • Unrest, confusion
• Dopamine agonist withdrawal syndrome
  • Etiology: abrupt discontinuation of dopamine agonist therapy
  • Clinical features: similar to malignant hyperthermia and neuroleptic malignant syndrome → hyperthermia and rigor; akinesia; reduced vigilance; increased creatine kinase levels, transaminases, and leukocytes
  • Treatment: intensive medical care, volume substitution, administration of L-DOPA, apomorphine, amantadine

Side effects of ergotamine-derived agonists (e.g., bromocriptine)

• Fibrosis (cardiac fibrosis, Raynaud disease, pleural pulmonary fibrosis, and retroperitoneal fibrosis)

Other substances

• NMDA antagonists (amantadine): side effects are similar to L-DOPA but much less pronounced
  • Ataxia
  • Livedo reticularis
  • Peripheral edema
• MAO-B inhibitors
  • Headache, dyskinesia, psychological disorders (e.g., hallucinations)
  • Inhibition of MAO-A with higher doses → reduced peripheral degradation of catecholamines → adrenergic side effects (e.g., tachycardia, sweating, nervousness)
• Muscarinic antagonists (anticholinergics): See “Antimuscarinic side effects.”
• COMT inhibitors
  • Gastrointestinal side effects
  • Dyskinesia and psychiatric symptoms (e.g., hallucinations or confusion)

NMDA antagonists 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!

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