Dopamine dysregulation syndrome in Parkinson's disease: from clinical and neuropsychological characterisation to management and long-term outcome

Abstract

Objective Dopamine dysregulation syndrome (DDS) refers to a compulsive pattern of dopaminergic drug misuse complicating Parkinson's disease (PD). To date, few data are available on DDS risk factors, cognitive profile and long-term outcome. Methods In this retrospective case-control study, consecutive PD outpatients fulfilling criteria for DDS were assessed over a 6-year period (2005)(2006)(2007)(2008)(2009)(2010)(2011). They were compared with 70 PD cases matched for age at onset, gender and disease duration, and with 1281 subjects with motor fluctuations and dyskinesias. DDS patients and matched controls underwent extensive neuropsychological assessment. Strategies for DDS patients management and the outcome at the last follow-up visit were recorded. Results Thirty-five patients with DDS were identified, reporting history of depression, family history of PD and drug abuse, greater difference between 'Off' versus 'On' motor symptoms compared to age-matched controls. They had younger age at onset (but not any gender difference) compared to general PD population. Cognitive profile of DDS did not show major abnormalities, including executive functions. DDS patients have been followed up for 3.2±2.1 years and remission was recorded in 40% of cases. Negative DDS outcome was significantly associated with poor caregiver supervision. Sustained remission occurred more commonly on clozapine and on duodenal levodopa infusion and subthalamic nucleus deep brain stimulation (STN-DBS) than on apomorphine pump treatment. Conclusions Clinicians should be aware of risk factors predisposing to DDS. Duodenal levodopa infusion and, less consistently, STN-DBS were more commonly associated with DDS remission. Effective caregiving plays a key role in long-term behavioural outcome.

Dyskinesias and impulse control disorders in Parkinson's disease: From pathogenesis to potential therapeutic approaches

“…A number of studies of drugs that act on serotonergic receptors have been undertaken in PD patients with ICD, with heterogeneous results having been obtained. Although several authors have reported beneficial effects of quetiapine or clozapine in ICD and DDS in PD patients (Cilia et al, 2014;Raja and Bentivoglio, 2012;Rotondo et al, 2010), others showed no improvement in a reduced number of patients with PG and punding (Kurlan, 2004). It is not clear if this heterogeneity is related to the small samples sizes, the type of ICD or other ICB or to other factors, but this topic warrants further investigation in order to better understand the mechanisms and treatment outcomes for each type of ICD and other ICB.…”

“…Controversial results (Baron and Dalton, 2003;Katzenschlager et al, 2004;Leey et al, 2009) Controversial results (Kurlan, 2004;Raja and Bentivoglio, 2012) Clozapine D4R and 5-HT 2A antagonist in a doble-blind placebo-controled trial (Durif et al, 2004) PG in a case report (Rotondo et al, 2010) DDS in a retrospective case-control study (Cilia et al, 2014) repetitive behavior in a case report (Kurlan, 2004) ICD reported in authors' experience (Raja and Bentivoglio, 2012) Citalopram SSRI binge eating, hypersexuality and compulsive shopping in pilot studies (Koran et al, 2003;McElroy et al, 2003;Wainberg et al, 2006) Fluoxetine SSRI in a open-label study (Durif et al, 1995) binge Controversial results (Mestre et al, 2013;Thomas et al, 2010) PG in a case report (Pettorruso et al, 2012) (Manson et al, 2001;Rascol et al, 1994) recurrent PG in a case report (Bosco et al, 2012) impulsivity in a phase III clinical trial (Papay et al, 2014) substance addiction in several studies (Adi et al, 2007;King et al, 2013;Morgenstern et al, 2012;Tiihonen et al, 2012) PG (Grant et al, 2008) and hypersexuality (Bostwick and Bucci, 2008;Raymond et al, 2010) Nalmefene…”

“…On the other hand, male gender, history of substance abuse, novelty seeking or compulsive/impulsive personality, and a familial history of addition or psychiatric disease, such as bipolar disorder or mania, have been associated with the development of ICD in PD Joutsa et al, 2012a;Voon et al, 2011;Weintraub et al, 2010b). DDS is mainly related to the use of levodopa or apomorphine (Cilia et al, 2014;Weintraub et al, 2015) and to a greater motor benefit in response to antiparkinsonian drugs (Cilia et al, 2014). Apart from this, DDS and ICD share some risk factors such as novelty-seeking or sensation-seeking traits (O'Sullivan et al, 2009) and premorbid depression.…”

“…Apart from this, DDS and ICD share some risk factors such as novelty-seeking or sensation-seeking traits (O'Sullivan et al, 2009) and premorbid depression. As for LID, youth is a risk factor for ICD (Wolters et al, 2008) and DDS (Cilia et al, 2014).…”

“…No data are available regarding punding and other ICB and the type of dopaminergic treatment. Moreover, DDS has a prevalence of about 3-4% (Cilia et al, 2014), while conflicting or no information is available regarding other ICB (Weintraub et al, 2015).…”