Impulse control and related disorders in Parkinson’s disease

Abstract

Neuropsychiatric disorders are common among patients with Parkinson's disease and may appear in any stage of the disease. However, these disorders often go undiagnosed and receive insufficient treatment. Observations in recent years have revealed that dopamine replacement therapy may lead to the development or worsening of conditions, such as gambling disorder, compulsive sexual behavior, compulsive buying and binge eating, in addition to punding and dopamine dysregulation syndrome. The pathophysiology of these disorders seems to be related to abnormal dopaminergic stimulation of the basal regions of the basal ganglia, especially via nigro-mesolimbic pathways. The aim of the present study was to perform a literature review on impulsivity, impulse control disorders and related conditions among patients with Parkinson's disease, with emphasis on their epidemiology, clinical characteristics and treatment.

Impulse Control Disorders in Parkinson's Disease. A Brief and Comprehensive Review

“…Pathological Gambling (PG) characterized by an excessive and uncontrollable “preoccupation with gambling and the excitement that gambling with increasing risk provides” despite financial loss and social problems (3, 7, 22, 25–27). PG was one of the earliest recognized ICDs in PD (3).…”

“…+ Treatment related: although ICDs have been reported to be associated to different drugs, such as L-dopa, amantadine and rasagiline, DA intake appears as the major risk factor for ICDs (1–5, 7, 8, 13–15, 17–22, 27, 29, 59, 60).…”

Effects of dopamine agonist treatment on resting-state network connectivity in Parkinson’s disease

“…Incidences of addictive behaviours and impulse control disorders, such as compulsive gambling and hypersexuality, are reported with increasing regularity in PD patients, having been observed in up to 10% of those treated with DA drugs (Dagher and Robbins, 2009;Weintraub et al 2010;Cilia and van Eimeren, 2011;Gao and Wu, 2016;Vargas and Cardoso, 2018). It is thus conceivable that cortico-subcortical networks subserving cognitive and motivational processes relevant for these behaviours would be altered differentially in PD On conditions, relative to PD Off and HCs (i.e., non-normalised).…”

“…Growing evidence suggests that, in a notable minority of PD patients, such non-motor, higher-order symptoms may be related to the same dopamine agonist (DA) medications used to treat primary motor problems (Cools, 2006;Dagher and Robbins, 2009;Cilia and van Eimeren, 2011;Antonelli et al, 2014). In particular, higherorder cognitive side effects of DA treatment often present as increased impulsive and compulsive behaviours and, in severe cases, neuropsychiatric syndromes, such as addictions and impulse control disorders (Dagher and Robbins, 2009;Weintraub et al 2010;Vargas and Cardoso, 2018).…”

“…Such regions comprise large-scale, cortico-striato-thalamic circuitry implicated in higher-order cognitive processes supported by dopamine, relevant for impulsivity and disturbed in PD (Honey et al 2003;Everitt and Robbins, 2005;Dagher and Robbins, 2009;Hacker et al 2012;Agosta et al 2014;Ruitenberg et al 2018). However, susceptibility to non-normalising DA effects varies across individuals, ostensibly in line with neurochemical and cognitive phenotypes (e.g., Dagher and Robbins, 2009;Buckholtz et al 2010;Housden et al 2010;O'Sullivan et al 2011;Vargas and Cardoso, 2018). Importantly, this cognitive-neuropsychiatric variability could reflect individual differences in baseline dopaminergic functioning, leading to differential sensitivity of neuronal systems to subsequent drug modulation: particularly within distinct striatal and other subcortical regions (Cools, 2006), but also in higher-level cortical areas (Cools and D'Esposito, 2011;Voon et al 2011;Ye et al 2011).…”