Behavioural adverse effects of dopaminergic treatments in Parkinson's disease: incidence, neurobiological basis, management and prevention

Abstract

Treatment of Parkinson's disease has traditionally focused on the management of motor disability while behavioural disturbances have received less attention. Recently, impulse control disorders and aberrant repetitive behaviours have surged to clinical relevance as they occur during dopamine replacement treatment (mainly with dopamine agonists) and worsen patient and caregiver quality of life. Patients are unable to adequately estimate the negative consequences of their actions and are prone to entertain compulsive reward-seeking activities. This review aims to summarize current evidence on the epidemiology of behavioural disturbances in Parkinson's disease, recent insights into their neurobiological basis and to discuss strategies for management and prevention. Studies from 1990 through to December 2008 were retrieved via searches of the Cochrane Database of Systematic Reviews and PubMed. The mechanisms underlying the development of behavioural disturbances in Parkinson's disease are debated but current evidence points to specific risk factors: male sex, young age at onset, underlying personality traits characterized by high impulsivity and novelty seeking, and personal or family history of addictive disorders. Specifically, in predisposed individuals dopamine replacement therapy leads to overstimulation of dopamine receptors within the mesocorticolimbic pathways and in turn to the development of addictive behaviours, such as impulse control disorders and compulsive medication intake. Since these disturbances affect individuals who have often unremarkable psychiatric history and no cognitive impairment, their identification and management is complex. Compulsive medication intake (described as 'hedonistic homeostatic dysregulation' or 'dopamine dysregulation syndrome') is commonly associated with fluctuations in advanced disease, while impulse control disorders frequently occur in early Parkinson's disease and within normal-range medication dosages. Management primarily requires reduction of dopaminergic therapy but psychosocial support is often required. Use of selective serotonin reuptake inhibitors in the dose used for obsessive compulsive disorders may help, while benefit from atypical antipsychotics is limited in most cases. Deep brain stimulation should be considered with caution in these subjects. Prevention is based on the identification of at-risk individuals and active monitoring. Given the social and potentially medical-legal consequences of these behaviours, we encourage treating physicians to discuss risks with patients before treatment is initiated.