Dopamine Replacement Affects Psychiatric Parkinson’s Symptoms

Celebrities often serve as ambassadors for a cause in both life and death, and in the recent tragedy involving the suicide of actor Robin Williams, that cause was bringing attention to the intertwined nature of Parkinson’s disease (PD) and depression.

But for improved awareness to translate to improved action, physicians need to better understand how depression and other mental health symptoms of PD—such as anxiety, fatigue, and lack of impulse control—arise, how they progress, and how they relate to the movement disorder.

“It really is a complicated issue,” said Daniel Weintraub, M.D., an associate professor of psychiatry and neurology at the Perelman School of Medicine at the University of Pennsylvania. “You have the psychosocial influence on mental health when someone finds out they have to deal with this progressive, incurable disease for the rest of their life, coupled with biological factors brought on by the actual nerve degeneration, not to mention potential side effects from various Parkinson’s medications.”

In some adventitious timing, however, Weintraub and colleagues published findings on the psychiatric progression of PD just days after Williams’ suicide.

Weintraub is part of the Parkinson’s Progression Markers Initiative (PPMI), a landmark observational study that will follow people newly diagnosed with PD over five years, with the goal of identifying new PD biomarkers. These new results, which were published August 15 in Neurology, represent preliminary data his team compiled on the cognitive and psychiatric aspects of PD over the first 24 months of evaluation.

Not surprisingly, depression and other psychiatric symptoms were more common in newly diagnosed PD patients than healthy controls, and their prevalence remained generally stable over the first 24 months, though some showed an upward trend. Apathy and psychoses, though, did rise more sharply, with the former nearly doubling from a prevalence of around 16 percent to 30 percent after two years, and the latter more than tripling from 3 percent to 10 percent.

Long-term dopamine replacement also resulted in some negative side effects; patients who had been on at least one type of dopamine-related medication for 12 months or more experienced higher rates of impulse control problems and daytime sleepiness than patients not on dopamine therapy. One-third of patients did show improvements in their fatigue levels, however, compared with only 11 percent of PD patients not on dopamine therapy. Other symptoms were unaffected by dopamine replacement therapy, including depression.

“Dopamine replacement therapy is highly effective against the primary motor symptoms of Parkinson disease, reducing disability and improving quality of life,” said Lisa Shulman, M.D., the Eugenia Brin Professor in Parkinson’s Disease and Movement Disorders at the University of Maryland School of Medicine. However, she noted that clinical decision making is founded on an informed comparison of all potential benefits and risks, and this longitudinal analysis will add value in that regard.

“Fortunately, impulse control disorders occurred in a relatively small number of patients. Also, the evidence that dopamine replacement therapy improved fatigue is important, as fatigue is a troubling Parkinson-related symptom,” she said.  

Weintraub’s group also looked at cognition and found some more interesting results. About one-fourth of patients who had no cognitive issues at the start of the study developed some impairment, but more than one-third who started with cognitive problems reverted back to normal after two years.

“Cognition decreased overall with time, but it wasn’t a straightforward decline,” said Weintraub. “And this type of data that you won’t see with single time point assessments reflects the tremendous strength of the PPMI study, and it’s a reason we wanted to publish some preliminary results to show others.”

Weintraub stressed the preliminary aspect; the PPMI enrolled 423 newly diagnosed, untreated PD patients and 196 healthy controls in total, though for this study’s publication only 96 PD patients and 83 healthy controls had reached the 24-month evaluation. “And people live with this disease for 10 to 20 years or even more, depending on age of onset,” Weintraub said. “So a two-year trend may not represent a true long-term effect.”

Given this long progression, Weintraub hopes the PPMI study will continue even beyond the initial five-year project. More time may provide more clarity or it may add some new twists, but either way it will address critical gaps in our knowledge of the neuropsychiatric side of PD.

The PPMI is sponsored and partially funded by the Michael J. Fox Foundation for Parkinson’s Research, with additional support coming from a consortium of industry groups, nonprofit organizations, and private individuals. ■

An abstract of “Course of Psychiatric Symptoms and Global Cognition in Early Parkinson Disease” can be accessed here.