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December 28, 2021

Adjunctive Therapies in Parkinson Disease—Have We Made Meaningful Progress?

Author Affiliations
  • 1Parkinson's Disease and Movement Disorders Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 2Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville
JAMA Neurol. 2022;79(2):119-120. doi:10.1001/jamaneurol.2021.4140

Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease. The prevalence of PD is increasing rapidly and is expected to double by 2040, to the extent that it has been called a Parkinson pandemic.1 The global burden of PD has also doubled in the last 20 years.2 The economic impact of PD has been substantially and consistently increasing, specifically with regard to the advanced stage of the disease.3 All of these factors indicate an urgent need for disease-modifying and ultimately curative and preventive therapies. Such therapies do not currently exist despite substantial efforts. On the positive side, PD has a large number of symptomatic therapies available for improvement of motor disability. Although levodopa has and remains the criterion standard, current oral preparations have the disadvantage of being associated with motor fluctuations and dyskinesia. As a result, levodopa adjunctive therapies have been a major target of drug development. All major classes of adjunctive therapies, such as dopamine agonists, catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase type B (MAO-B) inhibitors, have been found to be efficacious in reducing off time compared with placebo in well-designed studies and have been reported to be clinically useful based on an expert evidence-based systematic review.4 However, there is paucity of data on direct head-to-head comparison of the comparative efficacy, impact for quality of life, and health economic outcomes of different classes of adjunctive therapies.5

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1 Comment for this article
Adjunctive Therapies in Parkinson Disease – Is it Now Time to Focus on Non-Motor Symptoms and Quality of Life?
Ala Szczepura, BA, DPhil (Oxon); Dr Anil Gumber: BSc, MSc, PhD [Sheffield Hallam University]; Prof Deidre Wild: BA, RGN, MSc, PhD [Coventry University] | Centre for Healthcare Research, Coventry University, Priory St, Coventry CV1 5FB
As academics, including a person with Parkinson Disease (PD), we read with interest the recent editorial in JAMA Neurology on adjunctive therapies for PD.[1]. The Editorial considers the findings of a trial to determine long-term effectiveness (2001 – 2009) of adjuvant treatments added to levodopa to improve motor symptoms.[2] The Editorial highlights that, although a marginally significant benefit was found in the PDQ-39 motor domain, more meaningful outcomes such as hospitalization and long-term dementia showed no benefits.

In addition, it is essential to consider long-term outcomes on quality-of-life (QoL) of patients and their families and any broader economic consequences.
Measuring QoL beyond the 5-year EQ-5D-3L utility scores reported for patients in this trial will be necessary.[2] A recent systematic review demonstrates considerable deterioration beyond 5-years (50% lower QoL after 10 years), combined with significant impact on QoL of family members, and substantial societal costs linked to loss of employment and premature retirement.[3] We look forward to the results of a cost-utility analysis that will be reported separately for this trial.

Simuni and Okun’s editorial also concludes that there is an urgent need for more disease-modifying therapies for PD. Here, we would suggest that such therapies need to extend beyond conventional pharmaceutical interventions that focus on visible motor symptoms. More emphasis needs to be laid on less visible autonomic system non-motor symptoms (NMS) such as sleep problems and fatigue, pain, bladder and bowel problems, low blood pressure, loss of body image and mental health disorders. These have serious negative effects on symptom burden and quality of life for both patients and care partners. At the same time, NMS are also currently poorly reported to health professionals, and therefore often excluded from hospital records and unavailable as routine treatment outcome measures.[4]

Following the worldwide adoption of digital interventions and telecare during the COVID-19 pandemic, there is a need to consider how technology could support personalized PD self-management, focusing on both NMS and motor symptoms, especially if such interventions can slow deterioration of QoL.[5] As we come out of the pandemic, innovations are emerging to support self-management, reinforced by artificial intelligence.[6] The potential for such interventions to improve QoL and reduce healthcare and societal costs should now be seriously considered.

1. Simuni T, Okun MS. Adjunctive Therapies in Parkinson Disease-Have We Made Meaningful Progress? JAMA Neurol. 2022;79(2):119-120
2. Gray R et al. Long-term Effectiveness of Adjuvant Treatment: The PD MED Randomized Clinical Trial. JAMA Neurol. 2022;79(2):131-140.
3. Gumber A et al. Effects of Parkinson's on employment, cost of care, and quality of life (systematic review) Patient Relat Outcome Meas. 2019;10:321-333
4. Chaudhuri KR et al. The nondeclaration of nonmotor symptoms... Movement disorders. 2010;25(6):704-709.
5. Ellis TD, Earhart GM. Digital Therapeutics in Parkinson's Disease: Practical Applications and Future Potential. J Parkinsons Dis. 2021;11(s1):S95-S101
6. Perju-Dumbrava L et al. Artificial intelligence applications and robotic systems in Parkinson's disease (Review). Exp Ther Med. 2022;23(2):153.