Determining Appropriate Time to Initiate PD Treatment

According to the results of a new study, early treatment with levodopa for the treatment of Parkinson disease (PD) had no disease-modifying effect and it is not detrimental to disease course.  

Currently, levodopa is the main treatment used for the symptoms of PD. Researchers sought to determine whether levodopa also has disease-modifying effects that could provide guidance as to when in the course of the disease the treatment with levodopa can be initiated.  

In a multicenter, double-blind, placebo-controlled, delayed-start trial, the research team randomly assigned patients with early PD to receive levodopa (100 mg three times per day) in combination with carbidopa (25 mg three times per day) for 80 weeks (early-start group) or placebo for 40 weeks followed by levodopa in combination with carbidopa for 40 weeks (delayed-start group).  

According to the study findings, “patients with early [PD] who were evaluated over the course of 80 weeks, treatment with levodopa in combination with carbidopa had no disease-modifying effect.” 

We spoke with study author Rob di Bie, MD, PhD, neurologist and professor of Movement Disorders at the University of Amsterdam’s Faculty of Medicine, who explained why physicians can more assuredly tell their patients that there is no long-term detrimental effect of starting treatment with levodopa early.  

When is treatment with levodopa normally initiated? How does this compare with the objective of your study?

Levodopa can be started when the patient experiences disability in daily living. For a long time, levodopa was thought to have a negative long-term effect on Parkinson’s disease; there was fear it would hasten disease progression and that early use would increase the rate of dyskinesias in the long-term. Many neurologists tended to delay initiation and timely adjustments of levodopa. 

Following the publication of the ELLDOPA in 2004, the reluctance to use levodopa lessened to some extent. Knowing the effect of levodopa on the progression of Parkinson’s disease would have impact in clinical practice; i.e., if levodopa slows disease progression it should be started as soon as possible, if it accelerates disease progression levodopa sparing treatment would be advised, and if levodopa has no effect on disease progression it can be used as needed to suppress symptoms. 

What are the pros and cons of using levodopa?

Apart form nausea, which was slightly more frequent in the early-start group we did not find any downsides of starting levodopa early. Later in the disease, levodopa treatment is accompanied by response fluctuations, dyskinesias, and hallucinations; but this is not worsened by the earlier treatment. 

Briefly highlight the findings of your study.

The most important findings are that levodopa did not have a disease modifying effect, either beneficial or detrimental, and that starting levodopa 40 weeks earlier did not result in more levodopa related motor response fluctuations and dyskinesias at 80 weeks. 

What are the major takeaways from the study? When should levodopa be initiated, based on your findings?

Physicians can more assuredly tell the patient that there is no long-term detrimental effect of starting levodopa early. Especially, the patients that tended to be reserved regarding the use of levodopa may benefit as starting earlier with levodopa may improve their quality of life right at the time of diagnosis. 

Reference:

Verschuur CVM, Suwijn SR, Boel JA, et al. Randomized Delayed-Start Trial of Levodopa in Parkinson’s Disease [published online January 24, 2019]. N Engl J Med. 2019; 380:315-324. DOI: 10.1056/NEJMoa1809983