Amantadine and cognitive flexibility: decision making in Parkinson's patients with severe pathological gambling and other impulse control disorders

Introduction: Dopamine replacement therapy for Parkinson's disease (PD) was recently linked to the development of impulse control disorders such as pathological gambling (PG), hypersexuality, compulsive shopping, and binge or compulsive eating. Antiglutamatergic agents including amantadine (Ama) reduce these behaviors in PD and non-PD patients. The aim of our study is to evaluate the changes in executive functions, emotions, and reward/loss processing during Ama treatment in PD patients. Methods: Thirty-three patients affected by idiopathic PD were selected from a cohort of 1,096 PD patients and categorized in three different groups: ten affected by PG (PD-PG); nine PD patients with other impulse control disorder (PD-ICD); and 14 PD patient without any psychiatric disorder (PD-CTR-controls). For the neuropsychological evaluation, the following behavioral tasks where administered: the Stroop, the emotional Stroop, and the monetary reward/loss risk-taking tasks. Results: During Ama treatment, PD-PGs showed a decrease in risky choices and an increase in non-risky choices (t(9)=-2.40, P,0.05 and t(9)=2,67, P,0.05 uncorrected, respectively). Between-group comparison showed a significant decrease in risky choices for PD-PG with respect to PD-CTR (t(22)=-4.16, P,0.01), and a decreased accuracy for positive words in comparison between PD-PG and PD-ICD (t(17)=-7,49, P,0.01) and PD-PG and PD-CTR (t(22)=-4.29, P,0.01). No within- and between-group differences were observed for Stroop task. Discussion: Our data showed that Ama add-on therapy reduces hypersensitivity to reward and sustains activation toward uncertainty in PD-PG patients. These finding might explain the behavioral mechanism underlying the effect of antiglutamatergic drugs.