Nonmotor fluctuations are frequent and debilitating in PD.

BackgroundThe treatment of levodopa‐induced dyskinesia in Parkinson's disease (PD) is an unmet need with no approved drug therapy.ObjectiveThe purpose of this study was to investigate the efficacy and safety of 274 mg ADS‐5102 (amantadine) extended‐release capsules (equivalent to 340‐mg amantadine HCl) for levodopa‐induced dyskinesia in a randomized controlled trial.MethodsPD patients with ≥1 hour of troublesome dyskinesia and at least mild functional impact were randomized to placebo or ADS‐5102 once daily at bedtime for 13 weeks. The primary efficacy analysis was based on change from baseline to week 12 on the Unified Dyskinesia Rating Scale total score in the modified intent‐to‐treat population. OFF time was a key secondary measure.ResultsAt week 12, least‐squares mean change in the Unified Dyskinesia Rating Scale was −20.7 (standard error 2.2) for ADS‐5102 (n = 37) and –6.3 (standard error 2.1) for placebo (n = 38; treatment difference −14.4, 95% confidence interval −20.4 to −8.3, P < .0001), indicating improvement in levodopa‐induced dyskinesia. OFF time decreased 0.5 hours (standard error 0.3) for ADS‐5102 from a baseline mean of 2.6 hours and increased 0.6 hours (standard error 0.3) for placebo from a baseline mean of 2.0 hours (treatment difference −1.1 hours, 95% confidence interval −2.0 to −0.2, P = .0199). The most common adverse events (ADS‐5102 versus placebo) included dry mouth (13.5% versus 2.6%), nausea (13.5% versus 2.6%), decreased appetite (10.8% versus 0%), insomnia (10.8% versus 0%), orthostatic hypotension (10.8% versus 0%), constipation (8.1% versus 0%), falls (8.1% versus 5.3%), and visual hallucinations (8.1% versus 5.3%). Adverse events led to treatment discontinuation in 19% versus 8%, respectively.ConclusionADS‐5102 274 mg is an oral pharmacotherapy demonstrating a significant decrease in levodopa‐induced dyskinesia and improving OFF time. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

In Parkinson's disease, dopamine dysregulation syndrome (DDS) is characterized by severe dopamine addiction and behavioral disorders such as manic psychosis, hypersexuality, pathological gambling, and mood swings. Here, we describe the case of 2 young parkinsonian patients suffering from disabling motor fluctuations and dyskinesia associated with severe DDS. In addition to alleviating the motor disability in both patients, subthalamic nucleus (STN) deep brain stimulation greatly reduced the behavioral disorders as well as completely abolished the addiction to dopaminergic treatment. Dopaminergic addiction in patients with Parkinson's disease, therefore, does not constitute an obstacle to high-frequency STN stimulation, and this treatment may even cure the addiction.

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