Prescribing pramipexole? This patient case may have you rethinking your treatment approach
Industry Buzz
There have been many malpractice suits due to the ruinous effects of the dopamine compulsive issues.
—Mark J. Buchfuhrer, MD
Risk appears to be dose‑dependent and increases with longer treatment duration, with symptoms often improving or resolving after dose reduction or discontinuation of the offending agent.
—Katie Henn, PharmD, BCACP, CSP
If you’re still writing pramipexole for restless legs syndrome (RLS), a recent first-person account may prompt a pause before your next refill: A man in Los Angeles claims the drug pramipexole ruined his life by causing a compulsive gambling addiction.[]
Dopamine agonists are well documented to cause impulse control disorders (ICDs), including pathologic gambling, hypersexuality, compulsive shopping, and binge eating. Reported rates range from 6% to 17% overall, and they're even higher in some Parkinson’s disease cohorts.[]
At the same time, major guidelines have moved away from dopamine agonists as standard first-line therapy for RLS, citing risks of augmentation and behavioral complications.
Yet many clinicians continue to prescribe them, often because they work quickly and effectively... at least initially. Ahead: We break down what this latest case highlights, the key clinical considerations to revisit before initiating or continuing prescriptions, and alternatives to consider.
Here's what happened
The patient, J. Aaron Sanders, was prescribed the drug following a new diagnosis. “I barely slept for two weeks. A doctor diagnosed me with RLS and prescribed [pramipexole]. It worked. I slept. And for the first time in days, I felt like myself again. I would stay on that medication for nearly 20 years,” he wrote in an opinion piece for STAT News.[] “What I didn’t know at the time—and what no doctor told me—is that pramipexole carries a significant risk of impulse control disorders."
A few years after he started taking pramipexole, Sanders said entire paychecks were devoted to his gambling habit. He eventually became bankrupt, suicidal, and was admitted to the hospital twice.
Only after 20 years, when he was advised to stop taking the medication, did his gambling addiction resolve. “Within a week, the compulsions disappeared. It felt like an evil spirit had been exorcised. Two months later, I’d lost 30 pounds, was eating and sleeping normally, and for the first time in years, I felt clear headed,” Sanders said.
Dopamine agonists and impulse control disorders
Research suggests that long-term use of dopamine agonists cause ICDs in 6% to 17% of cases.[]
“The dopamine drugs, which include pramipexole (Mirapex), ropinirole (Requip), and transdermal rotigotine (Neupro patch), are all very well known to cause impulse control disorders,” Mark J. Buchfuhrer, MD, Clinical Associate Professor of Psychiatry and Behavioral Sciences at Stanford, tells MDLinx. “The behavior typically disappears within a few days to a few weeks after stopping the dopamine drug. I have seen many patients who have gambled away hundreds of thousands of dollars, and for some even over a million dollars, due to their drug-driven compulsive behaviors.”
There have been many malpractice suits due to the ruinous effects of the dopamine compulsive issues.
—Mark J. Buchfuhrer, MD
Dopamine agonists are also prescribed for Parkinson’s disease. Patients in this group may similarly experience ICDs as a side effect of the medication.
“ICDs associated with dopamine agonists occur more frequently in Parkinson’s disease than in restless legs syndrome,” says Katie Henn, PharmD, BCACP, CSP, Neurology Clinical Pharmacist at the Comprehensive Epilepsy Center and Movement Disorders Clinic at The University of Kansas Health System.
Reported prevalence ranges from 2.6% to 34.8% in Parkinson’s disease and 7.1% to 11.4% in restless legs syndrome.[] “Risk appears to be dose‑dependent,” Dr. Henn says, “and increases with longer treatment duration, with symptoms often improving or resolving after dose reduction or discontinuation of the offending agent.”
What's not recommended
Dopamine drugs are no longer recommended as a standard therapy for restless legs syndrome. But Dr. Buchfuhrer says the drugs are still being prescribed due to lack of awareness among physicians.
“The drugs work remarkably well initially to control RLS symptoms. But with time, they worsen (augment) the RLS symptoms in the majority of RLS patients, making the disease much harder to treat,” he explains. “However, most physicians are currently not aware of these issues, and dopamine drugs are still the most commonly prescribed medications for RLS patients. This is despite [the fact] that different published guideline articles have recommended against the standard use of dopamine drugs.”
Takeaways for the Clinic
Screening
Ask about prior gambling, compulsive spending, binge eating, hypersexuality, substance use, or bipolar disorder. Baseline risk matters.[][]
Monitoring
Symptoms may emerge months to years after initiation—and often resolve after dose reduction or discontinuation. Earlier symptom onset or dose escalation may signal augmentation, which can compound long-term risk.
Evaluate iron status in all patients; consider IV iron (eg, ferric carboxymaltose) or oral ferrous sulfate when indicated.[]
Address exacerbating factors first, including alcohol, caffeine, certain antidepressants or antihistamines, and untreated obstructive sleep apnea.
Alternative treatment options
Updated RLS guidelines favor alpha-2-delta ligands (eg, gabapentin enacarbil, pregabalin) over routine dopamine agonist use for chronic persistent RLS.[]
Extended-release oxycodone and other low-dose opioids may be considered for refractory RLS, with careful monitoring for misuse and adverse effects.