Impulse Control and Related Disorders in Parkinson’s Disease

Abstract

Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual behavior, and eating, are a serious and increasingly recognized complication of dopamine replacement therapy in Parkinson’s disease (PD). Other impulsive-compulsive behaviors have been linked to dopaminergic medications; these include punding (stereotyped, repetitive, purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive medication overuse). ICDs have been most closely related to the use of dopamine agonists (DAs), particularly at higher dosages; in contrast, DDS is primarily associated with shorter-acting, higher-potency dopaminergic medications, such as apomorphine and levodopa. Risk factors for ICDs may include male sex; younger age; younger age at PD onset; a pre-PD history of ICD(s); personal or family history of substance abuse; bipolar disorder; gambling problems; and impulsive personality traits. The primary treatment of ICDs in PD is discontinuation of DA therapy. Not all patients can tolerate this, however, due to worsening motor symptoms and/or DA withdrawal syndrome (a severe, stereotyped drug withdrawal syndrome similar to that of other psychostimulants). While psychiatric medications are frequently used to treat ICDs in the general population, there is no empirical evidence to suggest that they are effective in PD. Given the paucity of treatment options and potentially serious consequences of ICDs in PD, it is critical for patients to be monitored closely for their development. As empirically validated treatments for ICDs emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.

Dopamine-dependent corticostriatal synaptic filtering regulates sensorimotor behavior

“…Lesion of striatal DA in PD results in a loss of ability to engage in appropriate motor response to environmental cues. While substitution of DA by l -DOPA or D2-R agonists provides effective therapy, they also trigger undesired excessive behaviors in patients (Weintraub and Nirenberg, 2013). Here, we find parallel phenomena in DA hemilesioned mice, in that l -DOPA elicited an overactive sensorimotor response on the side corresponding to the DA lesion: differences between the two sides would in principle identify DA-regulated corticostriatal synaptic properties that mediate DA-dependent behavioral responses to environmental stimuli.…”

“…DA replacement therapies can however trigger excessive behavioral responses to environmental stimuli (Weintraub and Nirenberg, 2013) including dyskinesias (Fahn, 2005) and impulse control disorders (Voon et al, 2011). These responses increase in incidence and severity of these responses during prolonged therapy (Fahn, 2000), but sensitized responses to DA agonists occur immediately after the first administration of the drug to DA lesioned animals (Cenci et al, 1998; Morelli et al, 1989; Nadjar et al, 2009), and dyskinesias can be elicited from the first dose of l -DOPA in patients with inherited defects in DA synthesis (Pons et al, 2013).…”

Delay Discounting of Reward and Caudate Nucleus Volume in Individuals with α-Synuclein Gene Duplication before and after the Development of Parkinson’s Disease

“…A possible explanation is that both abnormally increased and decreased volume of the striatum may cause dysfunctional impulse control, which exhibits a considerable amount of variability in different forms of neuropsychiatric disorders. However, it cannot be excluded that impulsivity was the consequence of l -DOPA medication [21,26]. …”

“…None of the patients showed ‘on-off’ motor fluctuations at the time of testing. Impulsive-compulsive spectrum behavior was evaluated according to previously published criteria and definitions (gambling, hypersexuality, compulsive shopping, eating, or medication use, and punding) [20,21]. We assessed cognitive decline with the Mini-Mental State Examination (MMSE) [22] (table 1).…”

The prominent role of serotonergic degeneration in apathy, anxiety and depression inde novoParkinson’s disease

“…Beyond the well-known role of nigrostriatal dopaminergic dysfunction in the pathophysiology of Parkinson's disease motor symptoms (Brooks et al, 1990;Boileau et al, 2009), dopaminergic disruption of the mesolimbic and mesostriatal pathways is involved in the occurrence of several non-motor manifestations, such as apathy, depression, anxiety, fatigue, or impulse control disorders (Remy et al, 2005;Weintraub et al, 2005Weintraub et al, , 2015aAarsland et al, 2009;Boileau et al, 2009;Chaudhuri et al, 2009;Pavese et al, 2010;Thobois et al, 2010;Pagonabarraga et al, 2015;Castrioto et al, 2016). In addition, increasing lines of evidence support a specific causal role of serotonergic dysfunction in the pathogenesis of several parkinsonian signs, such as tremor and dyskinesia, but also depression, fatigue, cognitive decline and hallucinations, at moderate-toadvanced stages of the disease (Doder et al, 2003;Boileau et al, 2008;Pavese et al, 2010;Politis et al, 2010b;Ballanger et al, 2012).…”