Is There a Link Between Drugs for Parkinson Disease and Gambling Disorders?

Pathological gambling was recently identified as a complication of it’s the pharmacological treatment of Parkinson disease.¹ In fact, pathological gambling is an issue for 2.2% to 7% of patients with Parkinson disease on medication — higher than the general population.^1,2 Several studies have been conducted in an attempt to define the particular link with mixed results. Researchers do agree, however, that physicians who prescribe these drugs should warn their patients about this risk.

Risk Factors for Gambling Disorders

There are several risk factors for gambling disorders, including:^1,2

· Male gender

· Previous history of gambling behavior

· Duration of dopaminergic agonist use

· Family history of gambling

· Biological factors, such as changes in serotonin neurotransmission

The cause of drug-related gambling disorder isn’t fully understood, but it has been linked to an impaired function in the mesolimbic system, which is involved in risk and reward assessments.² In addition, it has been described as an adverse reaction associated with the use of drugs for Parkinson disease, mainly dopaminergic agonists at high doses.² However, while it’s widely recognized that dopamine agonists may induce behavioral disorders, it’s important to note that Parkinson disease itself is associated with pathological gambling as well as compulsive shopping and eating.¹

Recent Research on Gambling Disorders

The Italian Medicine Agency released a public statement warning of the increased risk for impulse control disorders, including pathological gambling, increased libido, and compulsive buying and eating, for patients taking dopamine agonists for Parkinson disease, restless leg syndrome, and endocrine disorders.¹ Now, summaries of product characteristics for apomorphine, bromocriptine, cabergoline, alpha-dihydroergocryptine, lisuride, pergolide, piribedil, pramipexole, quinagolide, ropinirole, levodopa and derivatives in association with entacapone/benserazide and carbidopa include language about their risk of causing impulse control disorders.¹

Subsequently, Italian researchers reviewed 94 suspected cases of gambling disorders from 2002 to 2018 that were associated with apomorphine, aripiprazole, cabergoline, levodopa, levodopa and derivatives in association with entacapone/benserazide and carbidopa, pergolide, pramipexole, ropinirole, and rotigotine.¹ More than 80% of gambling disorders in this group were related to pramipexole, ropinirole, and levodopa in association with entacapone/benserazide and carbidopa, while zero cases were reported for patients taking bromocriptine, alfa-dihydroergocryptine, lisuride, piribedil, quinagolide, modafinil, sertraline, citalopram, or lamotrigine.¹ The drug most commonly related to gambling disorder was pramipexole, the suspected medication in 56% of the cases reviewed.¹

A cross-sectional study of 3090 patients who were diagnosed with Parkinson disease and treated with either levodopa or a dopamine agonist found that those drugs were associated with a 2- to 3.5-fold increase in risk for impulse control disorder.¹

The Italian researchers stated that their efforts could not clarify the correlation between Parkinson disease, its pharmacological treatment, and pathological gambling.¹

Another group of researchers looked at the reports of drug-induced gambling disorders received by the Spanish Pharmacovigilance System. Between 1983 and 2016, 15 patients presented with gambling disorder.² Most had Parkinson disease and were being treated with pramipexole, ropinirole, rasagiline, or rotigotine (alone or in combination with other dopaminergic agents).² Specifically:²

· All patients were men between 46 and 84 years.

· The gambling disorders were classified as “serious.”

· The most frequently reported medicine was pramipexole (10 patients) followed by different fixed-dose combinations of levodopa (4 patients) or ropinirole (3 patients).

Almost half of the study sample showed complete recovery after the withdrawal of the suspected medicine.² The researchers of this study concluded that gambling disorders are an uncommon but serious adverse reaction to dopaminergic agents in the treatment of Parkinson disease.²

Implications for Clinical Practice

While further study is needed, the Italian researchers said that reducing the dose or discontinuing the use of dopamine agonists may lessen the occurrence of pathological gambling.¹ They recommended that clinicians closely monitor patients who are taking dopamine agonists for signs of pathological gambling.¹ They suggested providers look for patients who feel the need to bet ever larger sums of money to attempt to satisfy their desire for reward and make unsuccessful attempts to control their gambling habit.² These patients may present with other impulse-control disorders, such as hypersexuality, compulsive eating or shopping, and even suicidal ideation.²

References

1. Scavone C, Stelitano B, Rafaniello C, Rossi F, Sportiello L, Capuano A. Drugs-induced pathological gambling: an analysis of italian spontaneous reporting system [published online January 23, 2019]. J Gambl Stud. doi:10.1007/s10899-019-09828-1

2. Lanteri PF, Leguia A, Doladé NG, García GC, Figueras A. Drug-induced gambling disorder: a not so rare but underreported condition. Psychiatry Res. 2018;269:593-595.