Reports of Pathological Gambling, Hypersexuality, and Compulsive Shopping Associated With Dopamine Receptor Agonist Drugs

Abstract

IMPORTANCE 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. OBJECTIVES 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. DESIGN, SETTING, AND PARTICIPANTS 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. MAIN OUTCOMES AND MEASURES 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 for dopamine 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 D 3 receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D 3 receptor (n = 37; PRR = 8.6, P < .001). CONCLUSIONS AND RELEVANCE 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.

Partial mGlu5 Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects

“…Comorbidity with other psychiatric conditions, including depression and anxiety disorders, is commonly seen in substance use disorders, including cocaine abuse (Volkow, 2004;Vorspan et al, 2015). Pharmacotherapies developed for treating cocaine abuse have been largely unsuccessful (Shorter et al, 2015) and some purported treatment mechanisms elicit or exacerbate unwanted symptoms (eg, depression, anxiety, increased impulsivity, cognitive impairments, or psychosis) (Homayoun et al, 2004;Kishi et al, 2013;Moore et al, 2014). Developing pharmacotherapies targeting cocaine addiction and associated comorbidities while lacking adverse effects may provide greater therapeutic efficacy as well as medication compliance, increased abstinence rates and improved overall treatment success.…”

The factors associated with impulse control behaviors in Parkinson's disease: A 2‐year longitudinal retrospective cohort study

“…DAs with preferential affinity for the D3 receptor have strong association with ICB (Moore, Glenmullen, & Mattison, 2014). Pergolide has D3 receptor affinity (Kvernmo, Hartter, & Burger, 2006), and its use has been reported to be risk factors for the development of ICB (Weintraub et al., 2006).…”

“…In addition, patients with moderate‐to‐severe dyskinesia had ICB more frequently than patients with only mild dyskinesia (Biundo et al., 2017). DA use and high doses of DA have previously been shown to increase the risk of ICB development (Moore, Glenmullen, et al., 2014; Weintraub, Koester, et al., 2010). …”

Gambling Disorder in the Context of Parkinson’s Disease

“…This has been attributed to selective D3 receptor stimulation. [31][32][33] Pramipexole and ropinirole, as well as the rotigotine transdermal patch have a high affinity for dopamine D3 receptors, an affinity that has been closely associated -although this remains disputed -with the emergence of impulse control disorders. 28 Some experts are of the opinion that continuous, rather than pulsatile, drug delivery might result in superior impulse control.…”