The last two decades have observed a strong push to initiate dopamine agonist therapy for many Parkinson’s disease patients. However, recently there has been a move away from this approach. The hesitation about agonist therapy has mainly concerned the worrisome impulse control-related side effects, though there are other potential adverse effects reported from agonist use. Compulsive shopping, gambling, hypersexuality, personality change and binge eating can all inadvertently lead to financial ruin, marital distress or other life-altering circumstances in many patients on agonist therapy. In this month’s What’s Hot in PD? column, I will address the issue of whether doctors should be warning their patients about agonist-related side effects.
Pedro Garcia-Ruiz and colleagues conducted a study using 2.7 million serious domestic and foreign adverse drug events reported to the FDA between 2003 and 2012. There were 710 events reported for dopamine receptor agonist drugs and 870 for other dopamine receptor drugs. The agonist drugs were strongly associated with impulse control disorders. Two of the most common drugs used in Parkinson’s disease, Pramipexole and Ropinerole, had the strongest associations (Garcia-Ruiz, 2014, Okun MS, 2015).
It was clear that the dopamine agonists were strongly associated with the occurrence of impulse control disorders. The Parkinson's Foundation Parkinson’s Outcomes Project, the largest clinical study of Parkinson’s in the world, has more than 8,500 people with Parkinson’s enrolled and contains a wealth of data. Parkinson's Foundation Chief Mission Officer, Peter Schmidt, PhD, decided to examine this data to see what it included that could shed light on this issue and ultimately inform better Parkinson’s care.
By using a composite of six important research measures collected across the Parkinson's Foundation Centers of Excellence network, Dr. Schmidt was able to attain results informing us that a more prudent use of dopamine agonists was associated with better outcomes, but only to a certain point. Interestingly, one finding indicated that the centers that achieved the best outcomes were actually heavy users of dopamine agonists. Some of the worst outcomes were seen in centers using the agonists the least, so experience may have been an important factor (Okun MS, 2010, and personal communication with Dr. Peter Schmidt).
It is now confirmed that dopamine agonists are associated with impulse control disorders. Data from the FDA and many other sources support this association. One important piece of information missing from recent studies is the notion that the dopamine agonist patch, Rotigotine, may have a lower incidence of impulse control issues. This is something that we should all keep in mind. Two large, recent studies have shown this diminished incidence, and though it is unclear why, it may have something to do with the continuous delivery system. Pramipexole and Ropinerole have both answered with their own extended release formulations, but large-scale direct comparisons have not been performed and we do not know if these formulations decrease the incidence of dopamine agonist induced impulse control issues (Okun MS, 2015).
The bottom-line for patients is that dopamine agonists may be helpful for some, but not all patients. The large incidence (1:6) of impulse control disorders has been strongly associated with their use should prompt practitioners to warn patients and family members about these issues. Remember, an impulse control disorder may be pleasurable, and therefore patients may hide the issue from friends and family. A prospective monitoring plan should be initiated along with the dopamine agonist therapy. The safest plans involve spouses, caregivers and friends who can feedback any behavior directly to the prescribing physician. Patient consent to a prospective monitoring plan is necessary before implementation.
Garcia-Ruiz PJ, Martinez Castrillo JC, Alonso-Canovas A, et al. Impulse control disorder in patients with Parkinson's disease under dopamine agonist therapy: a multicentre study. Journal of neurology, neurosurgery, and psychiatry 2014;85:840-4.
Okun MS, Siderowf A, Nutt JG, et al. Piloting the NPF data-driven quality improvement initiative. Parkinsonism & related disorders 2010;16:517-21.
Samuel M, Rodriguez-Oroz M, Antonini A, et al. Management of impulse control disorders in Parkinson's disease: Controversies and future approaches. Movement disorders : official journal of the Movement Disorder Society 2015;30:150-9.
Okun MS. 10 Breakthrough Therapies for Parkinson’s Disease. Books4Patients, 2015.
You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease. You can read more from Dr. Okun in the What's Hot in PD? archives.