Pramipexole and Compulsive Gambling: What Are the Odds?

Joanna M. Pangilinan, PharmD

Disclosures

March 03, 2011

Question

If I'm prescribing pramipexole, what do I need to know about a patient's risk of developing an impulse control disorder?

Response from Joanna M. Pangilinan, PharmD
Pharmacist, Department of Pharmacy, University of Michigan, Ann Arbor

A 60-year-old woman with restless legs syndrome (RLS) lost about $6000 per month due to an "uncontrollable urge" to play slot machines.[1] A 70-year-old woman with Parkinson disease (PD) bought rabbits every day "like an addiction."[2] A wealthy 79-year-old man with RLS spent more than $50,000 on cars for 2 young girlfriends and $1.25 million on a penthouse for a third girlfriend.[1]

What do these people have in common? All had been taking a dopamine agonist.

Impulse control disorders (ICDs) are characterized by the failure to resist pursuing an activity, leading to excessiveness and ultimately harming the patient or others. Such disorders are underreported and include pathological gambling, compulsive sexual behavior, and compulsive buying. Binge or compulsive eating also share features of ICDs.[3]These conditions can have devastating personal and financial consequences to the patient and others.

PD and RLS are thought to be disorders of dopamine pathways in the basal ganglia.[4]Studies in both PD[5,6] and RLS[1] show that ICDs may occur more frequently in patients receiving dopamine agonists.

Weintraub and colleagues[5] performed a cross-sectional study of more than 3000 patients with PD receiving routine clinical care. They found that 13.6% of those patients had an ICD, and the use of a dopamine agonist was associated with a 2- to 3.5-fold increased likelihood of having an ICD.

Cornelius and colleagues[1] studied the frequency of ICDs in patients with RLS being treated with dopamine agonists. Two control groups were used: patients with obstructive sleep apnea, and patients with RLS who had never taken dopamine agonists. On the basis of results from a questionnaire and phone interviews, the frequency of ICDs in the treatment group was determined to be 17%. ICDs began after a mean treatment duration of 9.5 months.

In a separate study, Weintraub and colleagues reported that dopamine agonist use had the strongest association with active ICDs in PD; a history of ICD symptoms before onset of PD was also a significant predictor.[6] Other risk factors may include higher doses of dopamine agonist, younger age or younger age at onset of PD, unmarried status, self-reported history of ICD, personal or family history of substance abuse or bipolar disorder, impulsive personality style, and male sex.[3,7]New research suggests that patients with PD who are predisposed to ICDs also may be more functionally impaired.[8]

More research is needed to identify risk factors that may predispose patients with RLS to ICDs.[1] Patients with mood and stress states had an increased risk for ICDs while taking usual doses of dopamine agonists.[9]Cornelius and colleagues found that patients with ICDs were more likely to have depression as well.[1]

The dopamine agonist pramipexole is indicated to manage symptoms of PD and RLS,[10] and pramipexole is the most widely prescribed dopamine agonist in the United States.[8] Studies have not found significant differences between the available dopamine agonists in terms of their association with ICDs.[5,8]In addition, the association between the dopaminergic agent levodopa and ICDs is unclear.[3]

Recommendations

The manufacturer of pramipexole has provided guidance for the use of this drug,[10]and additional recommendations regarding dopamine agonist use in PD have been published by Weintraub[3]:

  1. Obtain a careful patient history before initiation of therapy; ask patients about any personal or family history of ICD or related behaviors.[3]

  2. Educate patients and caregivers about ICDs.[3]

  3. Use the lowest effective dosages of dopaminergic agents.[3]

  4. Ask patients and caregivers about the development of any new or increased urges during therapy (these behaviors may not seem abnormal to the patient).[10]

  5. Monitor patients and screen regularly for multiple ICD behaviors (eg, the Minnesota Impulsive Disorders Interview helps determine compulsive gambling, sexual, and buying behaviors).[3]

  6. Clinically significant ICDs warrant consideration of immediate reduction or tapered discontinuation of dopamine agonist therapy.[3,7,10] Urges were reported to resolve when the dosage was decreased or stopped;[10]the risk/benefit of further therapy depends on the severity of PD/RLS symptoms, the severity of ICD symptoms, and available treatment alternatives.[3]Case reports suggest that switching to a different dopamine agonist or undergoing counseling may provide some benefit.[3]

  7. Alternative pharmacologic agents should be considered on a case-by-case basis, and their use depends on patient- and disease-specific factors. Other agents for PD include monoamine oxidase B inhibitors, catechol-O-methyltransferase inhibitors, anticholinergics, and amantadine.[11] For RLS, off-label alternatives include benzodiazepines, opioids, gabapentin, and pregabalin.[4]

  8. If an ICD is suspected and the clinician needs assistance with assessment and treatment, the patient should be referred to a psychiatrist for evaluation and management.[3]

Rapid recognition and management of impulsive behavior are imperative in patients receiving dopamine agonists. Clinicians should monitor all patients receiving these medications and instruct patients and caregivers to report new or increased impulsive behavior. Early detection may help minimize the consequences of these potentially devastating behaviors.

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