Compulsive use of dopaminergic drug therapy in Parkinson's disease: reward and anti-reward

Mov Disord. 2010 May 15;25(7):867-76. doi: 10.1002/mds.22898.


A few Parkinson patients develop a disabling pattern of compulsive dopaminergic drug use ("dopamine dysregulation syndrome"-DDS). DDS patients commonly identify aversive dysphoric "OFF" mood-states as a primary motivation to compulsively use their drugs. We compared motoric, affective, non-motor symptoms and incentive arousal after overnight medication withdrawal and after levodopa in DDS and control PD patients. Twenty DDS patients were matched to 20 control PD patients for age, gender, and disease duration and underwent a standard levodopa challenge. Somatic symptomatology, positive and negative affective states, drug effects, reward responsivity, motor disability, and dyskinesias were tested in the "OFF"-state after overnight withdrawal of medications, and then after a challenge with a standard dose of levodopa, after a full "ON"-state was achieved. In the "OFF"-state, DDS patients reported lower positive affect, and more motor and non-motor disability. In the "ON"-state, DDS patients had higher expressions of drug "wanting," reward responsivity, and dyskinesias. Positive and negative affect, non-motor symptomatology, and motor disability were comparable. These findings suggest that affective, motivational, and motoric disturbances in PD are associated with the transition to compulsive drug use in individuals who inappropriately overuse their dopaminergic medication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affect / drug effects
  • Compulsive Behavior*
  • Dopamine Agonists / adverse effects
  • Dopamine Agonists / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Levodopa / adverse effects
  • Levodopa / therapeutic use*
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*
  • Severity of Illness Index
  • Substance Withdrawal Syndrome / diagnosis
  • Substance Withdrawal Syndrome / epidemiology
  • Substance Withdrawal Syndrome / etiology
  • Surveys and Questionnaires
  • Treatment Outcome


  • Dopamine Agonists
  • Levodopa