Elsevier

The Lancet Neurology

Volume 2, Issue 10, October 2003, Pages 595-604
The Lancet Neurology

Review
Compulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry?

https://doi.org/10.1016/S1474-4422(03)00529-5Get rights and content

Summary

Dopamine replacement therapy (DRT) is the most effective treatment for Parkinson's disease (PD); it provides substantial benefit for most patients, extends independence, and increases survival. A few patients with PD, however, take increasing quantities of medication far beyond those required to treat their motor disabilities. These patients demand rapid drug escalation and continue to request more DRT despite the emergence of increasingly severe drug-induced motor complications and harmful behavioural consequences. In this article we detail the features of compulsive DRT-seeking and intake in PD, in relation to theories of compulsive drug use.

Section snippets

Is this syndrome a substance dependence disorder or an addiction?

It can be difficult to diagnose a DSM-IV “substance dependence disorder”44 in a patient with a progressive incurable neurological disease. Development of tolerance is difficult to detect when a symptomatic treatment relieves the incapacitating physical symptoms. DRT requirements increase as motor disability progresses. Pharmacological tolerance to the motor effects of DRT has been described, but is not a major management problem.45, 46 Patients also experience adverse effects if withdrawn from

Do models of psychostimulant addiction help to understand compulsive DRT use in PD?

Current theories of addiction incorporate the idea that drugs activate and, via neuroadaptive processes, change dopaminergic neurotransmission in the nucleus accumbens and related circuitry, altering important reward-related processes (although different theories posit different processes).49

Implications for management

Ideally, the risk of developing compulsive DRT use should be minimised, because once patients have developed the disorder, long term management becomes difficult. Differences between patients, and pharmacological and environmental factors should be taken into account when using DRT to treat patients with PD. The potential influence of factors that might lead to an increased susceptibility to both locomotor and incentive sensitisation can be minimised by accounting for sex-related,

Summary and conclusions

Compulsive use of DRT by patients with PD, although rare, is of both clinical and theoretical importance. The major theories of psychostimulant addiction may help explain some of the phenomena seen in the dopamine dysregulation syndrome. All of the major theories can partly explain the syndrome, but it is unlikely that any one theory can explain all the features. The theories are not necessarily mutually exclusive, and dopamine dysregulation syndrome may not represent a unitary phenomenon with

Search strategy and selection criteria

Data for this review were identified by searches of MEDLINE, Psychlnfo, PubMed, and Web of Science databases, together with references from relevant articles. We used the search terms “abuse”, “addiction”, “agonist”, “apomorphine”, “approach”, “bromocriptine”, “cabergoline”, “dependence”, “dopamine”, “dyskinesias”, “euphoria”, “habit”, “hedonic”, “hoarding”, “levodopa”, “mood”, “nucleus accumbens”, “Parkinson's”, “pergolide”, “place preference”, “pleasure”, “pramipexole”, “psychiatric”,

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