Dopamine receptor agonists may be associated with impulse control disorders

1. Dopamine agonist drugs are used in the treatment of Parkinson disease, restless leg syndrome, and hyperprolactinemia.

2. Dopamine agonist drugs may be associated with compulsive gambling, hypersexuality, and binge eating or shopping.

Evidence Rating Level: 3 (Average)

Study Rundown: Previous work has suggested that impulse control disorders, such as compulsive gambling, hypersexuality, and binging behaviors are associated with the use of dopamine (DA) receptor agonists. Abnormalities in dopaminergic neurotransmission are implicated in the pathogenesis of Parkinson disease, restless leg syndrome, and hyperprolactinemia, prompting the use of DA agonists for these disorders. This study sought to corroborate the current evidence by conducting a retrospective analysis of adverse events reported by the US Food and Drug Administration (FDA) from 2003-2012.

DA agonists, most notably pramipexole and ropinirole, were directly associated with impulse control behaviors. The authors of this study suggest that more prominent warnings as part of prescribing information are warranted for these medications. Notably, this study is limited by its design. Searching for case reports based on search terms does not provide sufficient evidence of a casual relationship between use of a particular drug and an impulse control disorder. Further, the number of case reports written and subsequently released to the public may not truly reflect the incidence of such disorders. It is possible that not all cases of impulse control disorders are accurately recognized and reported. A further confounding factor is the increased media coverage of such side effects from dopaminergic drugs, which may result in over-reporting. Controlled studies are necessary for further evaluation of such phenomena.

Click to read the study, published today in JAMA Internal Medicine

Click to read an invited commentary published in JAMA Internal Medicine

Relevant Reading: Dopamine Agonists and Pathologic Behaviors

In-Depth [retrospective case series]: Data for this study was obtained from FDA records available to the public. Approximately 2.7 million events of all types were identified. Of these, 1,580 events represented impulse control disorders (i.e., pathological gambling, hypersexuality, compulsive shopping) and were identified by searching for terms related to these disorders. A proportional reporting ratio (PRR) was calculated by comparing the proportion of target events (e.g., impulse control events for a drug/total events for a drug) with the ratio of all other impulse control events to all other drug events. This PRR is analogous to relative risk.

Overall, the case reports of impulse control disorders in patients using DA agonists had a median age of 55 years, and 65% of those patients were male. The PRR for all DA agonists studied (the six currently available in the US) was 277.6 (p<0.001). There was a stronger association with impulse control disorders in drugs that have a particular affinity for the dopamine D3 receptor, notably pramipexole (n=410; PRR=455.9, p<0.001) and ropinirole (n=188; PRR=152.5, p<0.001). A weaker association was found for aripiprazole, an antipsychotic that functions as a partial agonist at the D3 dopamine receptor (n=37; PRR=8.6, p<0.001).

Image: PD

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