Movement Disorders

Dopamine precursor (Levodopa)

• Mechanism of action: Levodopa is converted into dopamine after it crosses the blood-brain barrier thus increasing intraparenchymal levels of dopamine.
• Side effects: Nausea/vomiting, dyskinesias, orthostatic hypotension.
• Carbidopa is given concurrently with levodopa to reduce the GI side effects and reduce levodopa’s peripheral plasma breakdown.
• Levodopa has a short half-life which can lead to motor fluctuations and peak-dose dyskinesia.
• Levodopa is safe in pregnancy.

COMT inhibitors (tolcapone and entacapone)

• Mechanism of action: Reduces methylation of levodopa and dopamine, which increases levodopa’s half-life.
• Ineffective when given alone but can prolong the duration of clinical response of levodopa when given together.
• The use of tolcapone requires liver enzyme monitoring.
• Side effects: Severe diarrhea and discoloration of urine.

MAO-B inhibitors (rasagiline and selegiline)

• Mechanism of action: Decreases the catabolism of dopamine, resulting in a greater peak effect and less wearing off when used in combination with levodopa.
  • Can also be used as monotherapy in early PD.
• Side effects:
  • Ingestion of tyramine heavy foods (aged cheeses, cured meats) can result in severe tachycardia and hypertensive crisis which at times can be fatal.
  • Concurrent use of SSRIs can lead to serotonin syndrome. 
• Decongestant medications and some narcotics may also interact with MAO-B inhibitors.

Direct dopamine agonists (DDA)

• Bromocriptine, pramipexole, ropinirole, rotigotine, and apomorphine
• Side effects: Impulse-control disorder, hallucinations, nausea, orthostatic hypotension, peripheral edema.
  • Pramipexole and ropinirole have been associated with excessive drowsiness and falling asleep while driving.
  • Can worsen dyskinesias when added to levodopa.
• Less likely to cause augmentation than levodopa.

Partial dopamine agonist and partial NMDA receptor antagonist (Amantadine)

• Mechanism of action: Has an anti-dyskinetic effect by reducing the frequency of abnormal involuntary movements due to levodopa.
• Side effects: Livedo reticularis

Anticholinergics (Trihexyphenidyl and benztropine)

• Can be used in younger patients (under 60) with tremor-predominant dysfunction, bradykinesia, postural instability, and/or rigidity.
• Side effects: Cognitive dysfunction, urinary retention, dry mouth, and GI disturbance.

Psychosis-related therapies

• Atypical antipsychotics
  •  Clozapine
    • Antipsychotic of choice for PD-related psychosis.
    • Mechanism of action: preferential inhibition of dopamine receptors in the frontal lobe and not the basal ganglia.
    • Side effects: bone marrow suppression
      • Requires blood count monitoring as a result
  • Quetiapine
    • Doesn’t have the risk of bone marrow suppression like clozapine but is likely not as efficacious.
• Pimavanserin
  • Only FDA approved medication specifically for Parkinson’s disease psychosis.
  • Mechanism of action: Serotonin 5-HT2A receptor inverse agonist and antagonist.

Deep Brain Stimulation (DBS)

• Used to treat the motor symptoms of PD but has no effect on its non-motor symptoms.
• Can be implanted into the contralateral side of major symptoms, or bilaterally.
• Significant cognitive dysfunction is a contraindication to DBS.
• Locations for DBS placement:
  • Ventral intermediate nucleus (VIM) of the thalamus: Improves tremor
  • Globus pallidus interna (GP_i) or subthalamic nucleus (STN) Improves tremor, bradykinesia, and rigidity.