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Dopamine Dysregulation Syndrome

An Overview of its Epidemiology, Mechanisms and Management

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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 ‘D2-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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Acknowledgements

The preparation of this paper was supported by the Reta Lila Weston Trust. The funding organization was not involved in the collection, management, analysis and interpretation of the data, and preparation, review or approval of the manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Reta Lila Weston Institute of Neurological Studies, University College London, 1 Wakefield Street, London, WC1N 1PJ, England

    Sean S. O’Sullivan & Andrew J. Lees

  2. Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, Australia

    Andrew H. Evans

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  1. Sean S. O’Sullivan
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  2. Andrew H. Evans
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  3. Andrew J. Lees
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Correspondence to Sean S. O’Sullivan.

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O’Sullivan, S.S., Evans, A.H. & Lees, A.J. Dopamine Dysregulation Syndrome. CNS Drugs 23, 157–170 (2009). https://doi.org/10.2165/00023210-200923020-00005

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