Medication Management of Parkinson's Disease: Early versus Advanced Stages

Parkinson's disease (PD) is a progressive neurodegenerative disease that mainly affects extrapyramidal motor function. Dopamine replacement therapy by levodopa (L-DOPA) is the best treatment for motor control. Moreover, dopamine agonists (DAs), monoamine oxidase type B (MAO-B) inhibitors, anticholinergic agents, catechol O-methyl transferase (COMT) inhibitors and amantadine are used mostly as adjuvant therapeutics. MAO-B inhibitors, especially selegiline may have potential neuroprotective effects, and anticholinergic agents play a role in tremor alleviation. Non-ergot DAs (e.g., pramipexole or ropinirole) substitute for the ergot ones (e.g., pergolide) due to having less cardiac valve problems. Initiation of either DAs or L-DOPA can be used for managing bradykinesia and rigidity in young and elderly patients, respectively. Chronic use of L-DOPA may induce motor complications, including motor fluctuations and dyskinesias in advanced PD. For reducing off time, inhibitors of COMT and/or MAO-B could be added. For reducing dyskinesias, amantadine may be considered. Pramipexole and ropinirole have been used recently as the initial treatment for young PD patients. Nonmotor symptoms (e.g., depression) are also important comorbidities in PD patients. Pramipexole and selegiline may be used in treating motor and depressive problems simultaneously in addition to their antiparkinsonian effects. All current antiparkinsonian medications alleviate merely extrapyramidal symptoms. Drugs for PD in the future should be targeting the disease progression.