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Dopamine Dysregulation Syndrome: An Overview of its Epidemiology, Mechanisms and Management
Abstract
Dopamine dysregulation syndrome (DDS) is a relatively recently described iatrogenic disturbance that may complicate long-term symptomatic therapy of Parkinson's disease. Patients with DDS develop an addictive pattern of dopamine replacement therapy (DRT) use, administering doses in excess of those required to control their motor symptoms. The prevalence of DDS in patients attending specialist Parkinson's disease centres is 3-4%. Amongst the behavioural disturbances associated with DDS are punding, which is a complex stereotyped behaviour, and impulse control disorders (ICDs), such as pathological gambling, hypersexuality, compulsive shopping and compulsive eating. We review the risk factors and potential mechanisms for the development of DDS, including personality traits, potential genetic influences and Parkinson's disease-related cognitive deficits. Impulsive personality traits are prominent in patients developing DDS, and have been previously associated with the development of substance dependence. Candidate genes affecting the dopamine 'D(2)-like' receptor family have been associated with impulsive personality traits in addition to drug and nondrug addictions. Impaired decision making is implicated in addictive behaviours, and decision-making abilities can be influenced by dopaminergic medications. In Parkinson's disease, disruption of the reciprocal loops between the striatum and structures in the prefrontal cortex following dopamine depletion may predispose to DDS. The role of DRT in DDS is discussed, with particular reference to models of addiction, suggesting that compulsive drug use is due to progressive neuroadaptations in dopamine projections to the accumbens-related circuitry. Evidence for neuroadaptations and sensitization occurring in DDS include enhanced levodopa-induced ventral striatal dopamine release. Levodopa is still considered the most potent trigger for DDS in Parkinson's disease, but subcutaneous apomorphine and oral dopamine agonists may also be responsible. In the management of DDS, further research is needed to identify at-risk groups, thereby facilitating more effective early intervention. Therefore, an increased awareness of the syndrome amongst treating physicians is vital. Medication reduction strategies are employed, particularly with regard to avoiding rapidly acting 'booster' DRT formulations. Psychosocial treatments, including cognitive-behavioural therapy, have been beneficial in treating substance use disorders and ICDs in non-Parkinson's disease patients, but there are currently no published trials of psychological interventions in DDS. Further studies are also required to identify factors that can predict those patients with DDS or ICDs who will derive benefit from surgical interventions such as deep brain stimulation.
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“These drugs act as artificial dopamine on those receptors, skipping over the need for natural dopamine (older L-Dopa medication promoted natural dopamine synthesis, but did not directly stimulate receptors) (O’Sullivan et al., 2009).”
From Evolving Concepts of Emotion and Motivation (2018) · cites this paper as O’Sullivan et al., 2009
In the citing paper
“This is called ‘dopamine dysregulation syndrome’ or DDS, and happens in 15% or more of Parkinson’s patients who are given newer ‘direct agonist’ medications that directly stimulate their brain dopamine D2/D3 receptors, especially at high doses.”
From Evolving Concepts of Emotion and Motivation (2018) · cites this paper as O’Sullivan et al., 2009
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Metadata
- Authors
- OʼSullivan, S. S., Evans, A. H., & Lees, A. J.
- Affiliations
- The Royal Melbourne Hospital (AU)
- University College London (GB)
- Venue
- CNS Drugs
- Published
- 2009
- Volume
- 23
- Issue
- 2
- Pages
- 157-170
- ISSN
- 1172-7047 (ISSN-L)
- OpenAlex
- W2130441789
- Cited by
- 265
- References
- 171
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 18 · 2023: 10 · 2022: 8 · 2021: 12 · 2020: 13 · 2019: 9 · 2018: 13 · 2017: 17 · 2016: 17 · 2015: 19 · 2014: 14 · 2013: 22 · 2012: 20
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS Drugs (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- dopamine dysregulation syndrome, Parkinson's disease, dopamine replacement therapy, impulse control disorders, punding, gambling addiction, hypersexuality, compulsive buying, compulsive eating, trait impulsivity, D2-like receptors, decision-making, ventral striatum, levodopa, apomorphine, dopamine agonists, cognitive behavioral therapy, deep brain stimulation, addiction models
- MeSH terms
- Clinical Trials as Topic, Cognition, Dopamine, Humans, Iatrogenic Disease, Parkinson Disease, Reward, Risk Factors, Syndrome, Dopamine Agonists, Substance-Related Disorders
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