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Levodopa Versus Dopamine Agonist after Deep Brain Stimulation in Parkinson's Disease

Study Rationale:                   
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for patients with advanced Parkinson's disease (PD). STN DBS improves motor symptoms, thus allowing a reduction of drug dose. However, most studies described the pharmacological therapy exclusively in terms of levodopa equivalents, with no further specification of the different agents used. Both levodopa and dopamine agonists can be used, however, there are no formal studies examining which type of antiparkinsonian medication may be more effective and/or better tolerated following STN DBS.

Our hypothesis is that dopamine agonists may be more efficacious than levodopa in treating non-motor symptoms after surgery (e.g., apathy and nocturnal restlessness), thus further improving quality of life following surgery. On the other hand, in comparison to levodopa, dopamine agonists may be associated with more side effects (e.g., impulse control disorders and mania) and less effective motor control.

Study Design:
This study is a prospective, single-blind parallel trial comparing levodopa monotherapy and dopamine agonist monotherapy after STN DBS. Patients will be enrolled in pairs, with one patient randomly assigned to one therapy and on to the other (20 patients for each study arm). Treatment assignment will be unmasked for the patient, but will be blinded for the neurologist programming DBS and evaluating the patient. Another neurologist will be in charge of medication adjustments. Primary outcome is the change in severity of non-motor symptoms as assessed by the Non-motor Symptoms Scale (NMSS) at a three-month follow-up visit after surgery.  

Impact on Diagnosis/Treatment of Parkinson’s Disease:             
In spite of an improvement of motor conditions, many patients develop apathy and depression following DBS surgery. This study will shed light on the best way to manage patients after STN DBS procedure, thus contributing to a further improvement of the surgical outcome.

Next Steps for Development:
Results of our study may provide new insights in the management of advanced PD after STN DBS, further leading to development of future larger trials.

Final Outcome

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for advanced Parkinson's disease (PD). This treatment delivers electrical pulses to brain cells to decrease motor symptoms. This study aimed to identify the best drug therapy for non-motor symptoms, such as apathy and nighttime restlessness, still present after surgery.

Forty people enrolled in this study, five of whom later withdrew. Of the remaining 35 people, 16 were assigned to treatment with a dopamine agonist (DA) and 19 to treatment with levodopa (LD). Although study participants were required to stop using the other medication for the duration of the study, 14 of 35 people failed to satisfy this requirement and received both DA and LD. Thus, the analysis included 3 groups: 1) 15 people on LD; 2) six people on DA; and 3) 14 people on LD and DA (DA-LD). Our preliminary data suggest that about 30% of participants required treatment with both DA and LD after STN DBS. While LD therapy was successful in 80% of participants, DA therapy, successful in only 17% of participants, was quite challenging after STN DBS.

Compared with the other two groups, people in the DA group scored more favorably on anxiety, activities of daily living and emotional well-being scales and worse on a motor function scale. Taken together, these findings suggest that patients tolerating DA therapy have a milder disease compared with patients on LD or on DA-LD. In contrast, people in the DA group had greater changes in perception compared with both LD and DA-LD groups, suggesting that delusions and hallucinations are specific side effects of DA. Impulse control disorders -- syndromes of compulsive gambling, hypersexuality and excessive shopping, to name a few -- improved in all study participants. Only one participant treated with DA had to gradually switch to LD in response to an increase in gambling.

January 2018


  • Alfonso Fasano, MD, PhD

    Toronto ON Canada

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