Parkinson's disease and behavioral addictions during a dopamine replacement therapy: psychopathological, neurological and pharmacokinetic profiles. – PARKADD

Traditionally considered as a motor disease, Parkinson's disease (PD) also affects cognitive and behavioral functions, via the impairment of the meso-cortico-limbic dopaminergic pathways. The abnormal activation of this "reward system" is considered to be the neurobiological substrate of addiction, explaining the links between MP and addictions, and especially between dopaminergic replacement therapy (DRT) and behavioral addictions (BA), such as pathological gambling, hypersexuality, compulsive buying, or binge eating. The BA have first been described as adverse effects of PD. Another hypothesis is a compulsive use of dopaminergic drugs, as part of the dopamine dysregulation syndrome (DDS). If the literature on the subject is rich, no study has ever attempted to differentiate, within the same population of Parkinson's patients with a BA, those for which there was a DDS from those for which there was an adverse effect of DRT. No study has never attempted to clarify the possible relationship between dose and pharmacodynamics of treatment on the one hand, and the development of BA on the other hand.
We propose to fill up these gaps by exploring the psychopathological, neurological and pharmacokinetic predictors of the development of a BA in patients with PD, as they have or not a DDS. Three patient profiles are then characterized: "BA-", "BA+/DDS-" and "BA+/DDS+".
In terms of psychopathology, we assume that the "BA+/DDS-" and "BA+/DDS+" groups differ on the presence of a misuse of DRT, the personal and family history of addiction and punding, the level of impulsivity (especially sensation seeking), and history of attention deficit disorder / hyperactivity.
On the neurological factors, we assume that some forms of PD are more likely to lead to cases of BA. Through the examination of patients and specific clinical evaluations, we hope to show a difference between the neurological profiles of the three groups, especially on the UPDRS III score in ON with the axial score.
For both the two clinical levels above-mentioned, the inclusion of 250 patients with PD will be required (150 "BA-", 75 "BA+/DDS-" and 25 "BA+/DDS+").
At last, on the pharmacological factors, we assume that the BA caused by DRT are associated with an overdose of the active ingredient, either because of misuse of the treatment, either because of an individual pharmacokinetic variability. We will define whether the pharmacokinetic parameters (distribution volume, clearance, absorption rate constant, elimination half-life) and exposure (area under the curve between 2 doses, residual concentration) of pramipexole significantly differ between the three patient profiles to establish a possible relationship of pramipexole plasma concentrations and pharmacodynamic effects. The pharmacokinetic part will be restricted to the study of a single molecule, pramipexole, in order to avoid methodological biases. For this part, 70 patients under Sifrol© will be included.
Three research teamsfrom the Nantes University Hospital (Federative institute of behavioral addictions / CIC 04 neurology / toxicology laboratory) will be involved. The fourth is a labeled team (EA4275) in the University of Nantes, specialized in statistics, and who works frequently with those above-mentioned.
The prospects of this study are to limit the development of BA in patients with PD treated by DRT, by identifying early those who are most at risk.