(FDA approved in bold)

• Parkinson’s disease (PD) including idiopathic PD, post-encephalitic parkinsonism, symptomatic parkinsonism
  
• Dopa-responsive dystonia (DRD)
  
• Restless legs syndrome (RLS)

• In PD, there is a loss of dopaminergic neurons in the substantia nigra and relative excess of cholinergic input. In DRD, there is a deficiency of tetrahydrobiopterin, a co-factor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis
  
• Levodopa crosses the blood-brain barrier and is converted to dopamine in the brain
  
• Carbidopa is a peripheral decarboxylase inhibitor that prevents levodopa from being metabolized in the gut, increasing CNS dopamine

• PD – hours, but may take 4–8 weeks to receive maximal benefit from a particular dose level when starting
  
• DRD – usually improves within days or weeks
  
• RLS – days to weeks

• PD – may require dose adjustments over time or augmentation with other agents
  
• DRD – effective at low doses

• PD – Bradykinesia, gait, and tremor should improve. Non-motor symptoms, including autonomic symptoms such as postural hypotension, depression, and bladder dysfunction, do not improve with carbidopa/levodopa. If the response is poor, reconsider the diagnosis of idiopathic PD. Drug-induced parkinsonism or atypical parkinsonism syndromes are possibilities
  
• RLS – Rule out peripheral neuropathy, iron deficiency, thyroid disease. Change to dopamine agonist or another drug

• For end-of-dose failure (wearing-off), early morning or nocturnal akinesia, and end-of-dose dystonia: increase frequency and decrease amount of each dose of medication, add a dopamine agonist with a longer half-life, add an MAO-B or COMT inhibitor
  
• For younger patients with bothersome tremor: anticholinergics may help
  
• For severe motor fluctuations and/or dyskinesias with good “on” time, functional neurosurgery is an option
  
• Amantadine may help suppress dyskinesias, although benefit is often short-lived
  
• Depression is common in PD and may respond to low dose SSRIs
  
• Cognitive impairment/dementia is common in mid-late stage PD and may improve with acetylcholinesterase inhibitors
  
• For patients with late-stage PD experiencing hallucinations or delusions, withdraw dopamine agonists and consider oral atypical neuroleptics (quetiapine, olanzapine, clozapine). Acute psychosis is a medical emergency that may require hospitalization
  
• For patients with DRD, anticholinergic drugs are also helpful
  
• For RLS, can add or change to dopamine agonist or anticonvulsant, such as clonazepam or gabapentin

• May cause elevation of liver enzymes or anemia. Regular blood work may be needed