Compulsive use of dopamine replacement therapy

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By Douglas J Lanska MD MS MSPH

In 2000, Giovannoni and colleagues defined "hedonistic homeostatic dysregulation" as a "neuropsychological behavioural disorder associated with substance misuse and addiction [and] recognized as a consequence of dopamine replacement therapy" (Giovannoni et al 2000). Such patients were noted to take increasing amounts of dopamine replacement therapy despite increasingly severe drug-induced dyskinesias and/or development of a cyclical mood disorder with hypomania or manic psychosis.

In 2009, Evans and colleagues defined "dopamine dysregulation syndrome" as the "compulsive use of dopaminergic medications well beyond the dose needed to optimally control motor disability and in the face of a mounting number of harmful physical, psychiatric, and social sequelae" (Evans et al 2009).

Many such patients have a maladaptive pattern of dopamine replacement therapy use and fulfill ICD-10 criteria for "addiction" (Lawrence et al 2003; Bearn et al 2004). This syndrome further implicates dopaminergic pathways in the development of substance abuse and addiction behavior (Lawrence et al 2003; Bearn et al 2004).


  • Compulsive use of dopamine replacement therapy
  • Dopamine dysregulation syndrome
  • Dopamine replacement therapy dependence syndrome
  • Hedonistic homeostatic dysregulation

Diagnostic criteria (adapted from Giovannoni et al 2000):

  • Parkinson disease responsive to levodopa
  • Use of increasing doses of dopamine replacement therapy in excess of those normally required to relieve parkinsonian signs and symptoms (eg, more than 2000 mg levodopa)
  • Pattern of pathological use of dopamine replacement therapy with any of the following:
    • Overdosing/binging with self-escalation of doses in excess of that required to alleviate motor impairment
    • Desire for increased dopamine replacement therapy in presence of significant/excessive/severe dyskinesias and despite being “on” motorically
    • Drug hoarding or drug-seeking behavior
    • Unwillingness to reduce dopamine replacement therapy
  • Self-induced features of intoxication in relation to dopamine replacement therapy with features of any of the following:
    • Hypomania
    • Mania
    • Cyclothymic affective syndrome
    • Self injury ideation/behavior
  • Development of a withdrawal state on reducing level of dopamine replacement therapy with dysphoric symptoms/features in the “off” state of any of the following:
    • Dysphoria/depression
    • Irritability
    • Anxiety
  • Impairment of social or occupational functioning (not in keeping with prior behavior), such as:
    • Arguments or difficulties with friends/family
    • Aggression/violence
    • Unexcused absence from work, loss of job, or legal difficulties
  • Duration of disturbed behavior at least 6 months 

Other commonly associated features:

  • Punding (repetitive, stereotyped, purposeless motor activity, such as incessant handling, sorting, or arranging of objects)
  • Hypersexuality
  • “Walkabout” (restlessness/akathisia with urge to walk especially during the “on” or “high” phase)
  • Pathological gambling or shopping
  • Alterations in appetite
  • Drug hoarding
  • Social independence or isolation in relation to drug-taking behavior (unlike common patterns of illicit drug abuse)