Hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies

Abstract

Hedonistic homeostatic dysregulation is a neuropsychological behavioural disorder associated with substance misuse and addiction. The disorder has been recognised as a consequence of dopamine replacement therapy (DRT) in 15 patients with Parkinson's disease. The syndrome typically develops in male patients with early onset Parkinson's disease, and can occur with orally and subcutaneously administered DRT. These patients take increasing quantities of their DRT, despite increasingly severe drug induced dyskinesias, and may develop a cyclical mood disorder with hypomania or manic psychosis. There is impairment of social and occupational functioning. Tolerance develops to mood elevating eVects of DRT and a negative aVective withdrawal state occurs if the drugs are withdrawn or doses decreased. The clinical features and guidelines for managing this syndrome are discussed. A set of diagnostic criteria for further investigating this condition is proposed. (J Neurol Neurosurg Psychiatry 2000;68:423-428) Keywords: Parkinson's disease; levodopa; apomorphine; addiction; drug misuse Parkinson's disease is defined clinically as an extrapyramidal motor disorder with signs of bradykinesia, rest tremor, rigidity, and postural instability. Pathologically, the disease is characterised by the presence of Lewy bodies and selective neuronal degeneration, particularly involving dopaminergic neurons in the substantia nigra pars compacta.1 The resulting dopamine depletion in nigrostriatal projections is thought to be responsible for the motor symptoms. Cell loss in dopaminergic neuronal populations giving rise to mesolimbic and mesocortical projections has been demonstrated in Parkinson's disease albeit it to lesser degrees than the nigrostriatal pathway.2 The deficiency of dopamine in these pathways may contribute to the bradyphrenia and mood disturbances which commonly accompany the motor manifestations of Parkinson's disease.Correcting the dopamine deficiency state in Parkinson's disease with levodopa or dopamine agonists attenuates the motor symptoms, and may also exert a beneficial eVect on the mood disorder and bradyphrenia. However, dopaminergic replacement therapy (DRT) in Parkinson's disease may also stimulate central dopaminergic pathways, which are intricately linked to the brain's reward system and are implicated in various states of addiction. 3 The stimulation of these pathways in some patients may initiate hedonistic homeostatic dysregulation, which ultimately leads to a behavioural disorder not too dissimilar from that associated with stimulant addiction. Although uncommon, this syndrome provides many challenges for the patient, their carers, and the treating physician. In this paper we describe the clinical features, propose a working definition, formulate a set of diagnostic criteria, and discuss management guidelines for this underrecognised phenomenon. Clinical syndrome CASE STUDYA 41 year old man presented with mild dystonic posturing of the left arm and hand, associated with mild rigidity and bradykines...

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