title: Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs.
abstract: OBJECTIVE
  Severe impulse control disorders involving pathological gambling, hypersexuality, and compulsive shopping have been reported in association with the use of dopamine receptor agonist drugs in case series and retrospective patient surveys. These agents are used to treat Parkinson disease, restless leg syndrome, and hyperprolactinemia.
  
  
  OBJECTIVE
  To analyze serious adverse drug event reports about these impulse control disorders received by the US Food and Drug Administration (FDA) and to assess the relationship of these case reports with the 6 FDA-approved dopamine receptor agonist drugs.
  
  
  METHODS
  We conducted a retrospective disproportionality analysis based on the 2.7 million serious domestic and foreign adverse drug event reports from 2003 to 2012 extracted from the FDA Adverse Event Reporting System.
  
  
  METHODS
  Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs.
  
  
  RESULTS
  We identified 1580 events indicating impulse control disorders from the United States and 21 other countries:710 fordopamine receptor agonist drugs and 870 for other drugs. The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders (n = 710; PRR = 277.6, P < .001). The association was strongest for the dopamine agonists pramipexole (n = 410; PRR = 455.9, P < .001) and ropinirole (n = 188; PRR = 152.5, P < .001), with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D3 receptor (n = 37; PRR = 8.6, P < .001).
  
  
  CONCLUSIONS
  Our findings confirm and extend the evidence that dopamine receptor agonist drugs are associated with these specific impulse control disorders. At present, none of the dopamine receptor agonist drugs approved by the FDA have boxed warnings as part of their prescribing information. Our data, and data from prior studies, show the need for more prominent warnings.
authors.affiliation: Institute for Safe Medication Practices, Alexandria, Virginia2Department of Epidemiology and Biostatistics, The George Washington University Milken Institute School of Public Health, Washington, DC.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Moore
authors.affiliation: Department of Psychiatry, Cambridge Hospital, Harvard Medical School, Cambridge, Massachusetts.
authors.forename: Joseph
authors.initials: J
authors.lastname: Glenmullen
authors.affiliation: McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, and Risk Sciences International, Ottawa, Ontario, Canada.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Mattison
mesh_terms: D000328:Adult; D000368:Aged; D000068180:Aripiprazole; D052160:Benzothiazoles / Q000009:adverse effects; D003192:Compulsive Behavior / Q000139:chemically induced*; D003258:Consumer Behavior; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D004348:Drug Labeling; D005260:Female; D005715:Gambling / Q000139:chemically induced*; D006801:Humans; D006966:Hyperprolactinemia / Q000188:drug therapy; D007175:Impulsive Behavior / Q000187:drug effects; D007211:Indoles / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy; D010879:Piperazines / Q000009:adverse effects; D000077487:Pramipexole; D015363:Quinolones / Q000009:adverse effects; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D012148:Restless Legs Syndrome / Q000188:drug therapy; D012189:Retrospective Studies; D012725:Sexual Behavior / Q000187:drug effects*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D007211:Indoles; D010879:Piperazines; D015363:Quinolones; D050637:Receptors, Dopamine D3; C046649:ropinirole; D000068180:Aripiprazole; D000077487:Pramipexole