Advanced Therapies for the Management of Dopamine Dysregulation Syndrome in Parkinson's Disease

Abstract

Background: Dopamine Dysregulation Syndrome (DDS) is an adverse non-motor complication of dopamine replacement therapy in Parkinson's disease. The current literature on this syndrome is limited, and it remains underdiagnosed and challenging to manage.

Objective: To assess the role of advanced therapies in the management of DDS.

Methods: We performed a retrospective chart review and identified patients who fit the inclusion criteria for DDS. They were classified according to risk factors that have been identified in the literature, motor and complication scores, intervention (medical or surgical) and outcome. Multivariate analyses were performed to analyze these characteristics.

Results: Twenty-seven patients were identified (23 males, mean age of onset: 49 ± 8.8 years). Average levodopa equivalent daily dose was 1916.7 ± 804 mg and a history of impulse control disorders, psychiatric illness, and substance abuse was present in 89%, 70% and 3.7% of the patients, respectively. Overall 81.5% of patients had symptom resolution at follow up, on average 4.8 ± 3.5 years after management, with medication only (7/9), levodopa-carbidopa intestinal gel (1/3), deep brain stimulation of subthalamic nucleus (10/13), or globus pallidus pars interna (2/2). Reduction of medications occurred with deep brain stimulation of subthalamic nucleus (P = 0.01) but was associated with a relapse in two patients.

Conclusion: Although the small sample size of some subgroups limits our ability to draw meaningful conclusions, our results did not suggest superiority of a single treatment option. Advanced therapies including deep brain stimulation can be considered in patients with DDS refractory to conservative measures, but outcome is variable and relapse is possible.

Keywords: Parkinson's disease; addiction; dopamine dysregulation syndrome; therapy.

FIG. 1

A: Levodopa equivalent daily doses before and after treatment. LEDD reduction was seen in all groups, except LCIG. The only significant dose reduction was appreciated with STN DBS (*: P = 0.01) B: Dyskinesia before and after treatment according to item 4.1 (time spent with dyskinesias) of MDS‐UPDRS‐IV. A significant reduction in dyskinesia was obtained with LEDD reduction (*: P = 0.04) and STN DBS (**: P = 0.01). Abbreviations: GPi, globus pallidus pars interna; LCIG, levodopa‐carbidopa intestinal gel; LEDD, levodopa‐equivalent daily dose; MDS‐UPDRS‐IV, Movement Disorders Society‐sponsored revision of the Unified Parkinson's Disease Rating Scale; STN, Subthalamic nucleus.