Levodopa-Induced Euphoria May Drive Addictions, Behavior in Parkinson's
ON-drug euphoria is related to the psychostimulant effects of dopaminergic treatments.
The effects of dopamine during ON-drug euphoria, characterized by hyperactivity and impulsivity in patients with advanced Parkinson's disease receiving levodopa, is associated with medication abuse and behavioral addictions, according to findings from a prospective analysis published in Movement Disorders.1
Patients with Parkinson's disease who receive levodopa therapy may experience nonmotor fluctuations based on their disease duration and severity, their age, and the presence of motor fluctuations.2 In this study, the researchers focused on neuropsychiatric fluctuations, which can be characterized by changes in mood, motivation, and anxiety while in ON and OFF states of drug therapy.3 The researchers prospectively evaluated data from a cohort of 102 patients with Parkinson's disease with levodopa-related motor complications to determine potential correlations between neuropsychiatric fluctuations and behavioral and dopamine addictions.
Patients with (n=51) and without (n=51) neuropsychiatric fluctuations were included in the analysis. The investigators observed a trend toward more severe motor OFF states according to the United Parkinson's Disease Rating Scale (P =.07), as well as for the size of the levodopa response (P =.07).
Compared with the group without neuropsychiatric fluctuations, patients with neuropsychiatric fluctuations had higher dopamine addiction rates (5.9% vs 21.6%; P =.02), a correlation that also existed in the multivariate analysis (odds ratio [OR], 8.9; 95% CI, 1.4-56.2; P =.02). Patients in the neuropsychiatric fluctuation group were also more likely to have behavioral addictions than patients without fluctuations (31.4% vs 19.6%), a finding considered significant in the multivariate model (OR, 3.76; 95% CI, 1.11-12.75; P =.033).
Dopamine and behavioral addictions occurred more frequently in the presence of ON-drug euphoria compared with its absence (27% vs 6.2% [P =.003] and 46% vs 13.9%; P <.001). No association was demonstrated between behavioral or dopamine addictions in the presence of OFF-drug dysphoria. In addition, there were more past occurrences of anxiety in the neuropsychiatric fluctuation group (37.3% vs 15.7%; P =.014).
On the basis of these findings, the investigators noted that "[t]he presence of neuropsychiatric fluctuations, and particularly ON-euphoria, should raise vigilance of the neurologist and call for active screening of behavioral and dopamine addictions."
- Delpont B, Lhommée E, Klinger H, et al. Psychostimulant effect of dopaminergic treatment and addictions in Parkinson's disease [published online July 24, 2017]. Mov Disord. doi: 10.1002/mds.27101
- Mart_ınez-Fern_andez R, Schmitt E, Martinez-Martin P, et al. The hidden sister of motor fluctuations in Parkinson's disease: a review on nonmotor fluctuations. Mov Disord. 2016;31:1080-1094.
- Maricle RA, Nutt JG, Valentine R, et al. Dose-response relation-ship of levodopa with mood and anxiety in fluctuating Parkinson's disease: a double-blind, placebo-controlled study.  Neurology. 1995;45:1757-1760.