Recognition of a dopamine replacement therapy dependence syndrome in Parkinson's disease: a pilot study☆☆Supplementary

Evans, Andrew; Kelleher, Michael J.; Turner, Kirsten; Lees, Andrew J.

doi:10.1016/j.drugalcdep.2004.06.005

Cited by 48 publications

(43 citation statements)

References 18 publications

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“…These patients demand rapid drug escalation and continue to request more levodopa despite the eventual emergence of increasingly severe drug-induced motor complications and harmful behavioural consequences [32]. Using a semi-structured questionnaire, these patients were found to suffer maladaptive therapeutic dependence on dopamine replacement therapy, fulfilling operational criteria of substance dependence [5]. Indeed, this syndrome closely resembles addiction to psychostimulants, with psychomotor agitation and euphoria, strong resistance to dose reduction, and withdrawal symptoms characterized by depression, dysphoria, irritability, anxiety, and impairment in occupational and social functioning [20,32].…”

Section: Dopamine Dependency Syndrome (Dds-2)mentioning

confidence: 99%

Parkinson’s disease-related disorders in the impulsive-compulsive spectrum

2008

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In Parkinson's disease (PD), there is increasing evidence for disorders in the impulsive-compulsive spectrum, related to the disease itself, to the pharmacological management of this disease or to both. These disorders comprise dopamine deficiency syndrome (with immediate reward seeking behaviour), dopamine dependency syndrome (with addictive behaviour), dopamine dysregulation syndrome (with both addictive behaviour and stereotyped behaviour) and impulse control disorders (such as pathological gambling, compulsive shopping, binge eating and hypersexuality). These disorders are especially seen in PD patients with young age of onset, higher doses of antiparkinsonian drugs, pre-existent or current depression, pre-existing recreational drug or alcohol use, and high novelty seeking personality traits.Dopamine is not only implicated in voluntary movement control but also plays a significant role in the brain's reward system and the modulation of behaviours. Therefore, most if not all drugnaïve PD patients will suffer dysphoria, leading to mild immediate reward seeking behaviour as a consequence of the striatal dopaminergic denervation. In some of these patients, during treatment, this may even lead to the intake of increasing quantities of levodopa, above those required to adequately treat motor parkinsonism, with all characteristics of a dopamine dependence syndrome. These patients may develop plastic changes in the striatal matrix leading to hyperkinesia, caused by extracellular striatal dopaminergic fluctuations due to pulsatile dopamine replacement therapy. As soon as these changes are also seen in the striatal striosomes, in the framework of a dopamine dysregulation syndrome, stereotyped behaviours (punding) may occur (supposedly due to dorsal versus ventral striatal overactivity). Finally, impulse control disorders are suggested as being pure adverse side-effects of dopamine replacement therapy. Obsessive-compulsive behaviour (caused by ventral to dorsal overactivity) so far has not been described in PD patients.Treatment of impulse control disorders is related to the underlying pathology. In the case of an intrinsic dopamine deficiency syndrome, treatment with dopamine replacement therapy, especially levodopa, will help. In the multifactorial (intrinsic and extrinsic) dopamine dependency and dysregulation syndromes, addictive behaviour might best be helped by psychosocial strategies, and punding by continuous dopaminergic receptor stimulation (or amantadine), hypothesized to reduce the plastic changes-induced hypersensitization. The extrinsic impulse control disorders might be best treated by reducing or replacing dopamine receptor agonists.

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Section: Dopamine Dependency Syndrome (Dds-2)mentioning

confidence: 99%

Parkinson’s disease-related disorders in the impulsive-compulsive spectrum

2008

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“…[2][3][4] These individuals typically request extra drugs and complain of developing tolerance to the effects of the drugs despite the external appearance of being well medicated and displaying disabling drug-induced abnormal involuntary movements (dyskinesias). 2,3 This syndrome is called "dopamine dysregulation" 4 (DDS), and many of these individuals fulfil core Diagnostic and Statistical Manual (of Mental Disorders) Fourth Edition diagnostic criteria for substance dependence due to the negative effects that their compulsive pattern of dopaminergic drug use has on social, psychological, and physical functioning 5 (eg, marital breakdown, among others). In animal models, L-dopa and dopamine agonists appear to share some of the psychomotor activating properties of commonly abused drugs.…”

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confidence: 99%

Compulsive drug use linked to sensitized ventral striatal dopamine transmission

Evans

Pavese

Lawrence

et al. 2006

Annals of Neurology

430

270

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“…Though those symptoms may be c o rrelated to mood fluctuation due to an intense off period, it may be considered a real withdrawal state commonly seen in other drugs dependence. Nevertheless, a withdrawal state from levodopa has not yet been confirmed 13 .…”

Section: Discussionmentioning

confidence: 99%

Dopamine dysregulation syndrome in Parkinson's disease: case report

Kümmer¹,

Maia²,

Salgado

et al. 2006

Arq. Neuro-Psiquiatr.

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-We report a 67-year-old man with Parkinson's disease for 9 years who developed compulsive use of levodopa. This phenomenon is the main feature of the dopamine dysregulation syndrome. Other related symptoms presented by our patient were mood fluctuation and increased writing activity suggestive of punding.KEY WORDS: Parkinson's disease, dopamine dysregulation syndrome, punding.Síndrome de desregulação dopaminérgica na doença de Parkinson: relato de caso RESUMO -Relatamos sobre um homem de 67 anos de idade com doença de Parkinson por 9 anos e que desenvolveu uso compulsivo de levodopa. Esse fenômeno é a principal característica da síndrome de desregulação dopaminérgica. Outros sintomas apresentados pelo paciente foram flutuações do humor e atividade de escrita aumentada, comportamento este sugestivo de punding. PALAVRAS-CHAVE: doença de Parkinson, síndrome de desregulação dopaminérgica, punding.Parkinson's disease (PD) is associated with a prog ressive dysfunction of the dopaminergic neuro t r a n smission in the basal ganglia. On pathological examination, the dopaminergic neurons in the pars compacta of the substantia nigra a re markedly re d u c e d , and cytoplasmic proteinaceous aggregates known as Lewy bodies are present in the residual neurons. Dopamine replacement therapy (DRT), with the dopamine precursor levodopa or synthetic dopamine agonists, is considered the mainstem of the pharm a c ological approach for the symptoms of PD 1 , 2 . However long-term DRT is commonly associated with a series of motor complications, such as dyskinesias and the o n -o ff phenomenon. More re c e n t l y, interest has been drawn to non-motor complications of PD and treatm e n t -related psychiatric symptoms, such as depre ssive disorders, fatigue, apathy and cognitive impairment 3 . We describe a man with PD since 58 year-old who developed compulsive use of levodopa. In off periods he presented severe non-motor symptoms, including craving for levodopa, intense feelings of dysphoria, worsening of depressive symptoms, painful tru n k sensations and profuse sweating. During peak dose period, he also became hypomanic and had diff i c u lty in perceiving his severe dyskinesias. This behavior has been recently described in literature as a quite r a renon-motor complication of DRT. This syndro m e of increased use of levodopa beyond that needed to achieve relief of motor symptoms, associated with disabling mood and behavioral features is re f e rre d by some authors as dopamine dysregulation syndrome ( D D S ) 4 , 5 . To the best of our knowledge, this is the first case of this syndrome re p o rted in the Brazilian l i t e r a t u re. The patient gave informed consent for this case report. CASEA 67-year-old man, married, a retired surgeon had PD for 9 years. He had no previous history of alcohol or any

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Recognition of a dopamine replacement therapy dependence syndrome in Parkinson's disease: a pilot study☆☆Supplementary

Cited by 48 publications

References 18 publications

Parkinson’s disease-related disorders in the impulsive-compulsive spectrum

Parkinson’s disease-related disorders in the impulsive-compulsive spectrum

Compulsive drug use linked to sensitized ventral striatal dopamine transmission

Dopamine dysregulation syndrome in Parkinson's disease: case report

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