Treatment of Advanced Parkinson's Disease

Juan C. Giugni; Michael S. Okun


Curr Opin Neurol. 2014;27(4):450-460. 

In This Article

Abstract and Introduction


Purpose of Review. Later stage Parkinson's disease, sometimes referred to as advanced disease, has been characterized by motor complication, as well as by the potential emergence of nonlevodopa responsive motor and nonmotor symptoms. The management of advanced stage Parkinson's disease can be complex. This review summarizes the currently available treatment strategies for addressing advanced Parkinson's disease.

Recent Findings. We will discuss the latest pharmacological strategies (e.g., inhibitors of dopamine-metabolizing enzymes, dopamine agonists, and extended release dopamine formulations) for addressing motor dysfunction. We will summarize the risks and benefits of current invasive treatments. Finally, we will address the current evidence supporting the treatment of nonmotor symptoms in the advanced Parkinson's disease patient. We will conclude by detailing the potential nonpharmacological and multidisciplinary approaches for advanced stage Parkinson's disease.

Summary. The optimization of levodopa is, in most cases, the most powerful therapeutic option available; however, medication optimization requires an advanced understanding of Parkinson's disease. Failure of conventional pharmacotherapy should precipitate a discussion of the potential risks and benefits of more invasive treatments. Currently, there are no comparative studies of invasive treatment. Among the invasive treatments, deep brain stimulation has the largest amount of existing evidence, but also has the highest individual per patient risk. Nonmotor symptoms will affect quality of life more than the motor Parkinson's disease symptoms, and these nonmotor symptoms should be aggressively treated. Many advanced Parkinson's disease patients will likely benefit from multi and interdisciplinary Parkinson's disease teams with multiple professionals collaborating to develop a collective and tailored strategy for an individual patient.


Despite the availability of medical and surgical treatments that improve Parkinson's disease motor symptoms, the disease will, in the majority of sufferers, lead to progressive disability.[1] Progression in later stages is characterized by motor complications inclusive of fluctuations and dyskinesia.[2] As Parkinson's disease progresses there is an emergence of a symptom constellation that may be nonresponsive to levodopa. This resistant symptom complex includes postural instability and falls, speech and swallowing difficulties, and nonmotor symptoms (NMS).[3]

Hoehn and Yahr[4] suggested that the mean time of Parkinson's disease progression to disability was 7 years in the prelevodopa era. However, in the postlevodopa era, the mean time from disease onset to wheelchair dependence was 14 years.[5] Parkinson's disease progression has been universally associated with increased disability and a diminished quality of life (QoL).[6–8]

Advanced Parkinson's disease is commonly defined by clinicians as stages 4 and 5 on the Hoehn and Yahr scale.[4] Other authors have suggested as an alternative definition that the onset of motor complications is a more reasonable description of advanced disease.[6,9,10] Additionally, the older definition does not differentiate Parkinson's disease patients who develop levodopa resistant symptoms, and those who become highly dependent on caregivers.[11] In this article, we will define advanced Parkinson's disease as the onset of motor complications, despite aggressive pharmacological and behavioral management. We will not exclude patients with NMS and/or levodopa resistant symptoms. We will present an evidence-based review of current treatment options for the management of motor and nonmotor complications of advanced Parkinson's disease (Figure 1).

Figure 1.

Suggested guideline for the management of advanced Parkinson's disease. BoNT, botulinum toxin; CBT, cognitive behavioral therapy; COMT, catechol-O-methyltransferase; CR, controlled release; DA, dopamine agonist; DBS, deep brain stimulation; EDS, excessive daytime sleepiness; GPi globus pallidus interna; H. Pylori, Helicobacter pylori; LCIG, levodopa carbidopa intestinal gel; MAO-B, monoamine oxidase-B; RBD, REM sleep behavior disorder; rTMS, repetitive transcranial magnetic stimulation; SNRIs, serotonin and norepinephrine reuptake inhibitors; SSRIs, serotonin reuptake inhibitors; STN, subthalamic nucleus; TCAs, tricyclic antidepressants.