Article In Brief
In a longitudinal study, researchers found patients who were taking dopamine agonists for Parkinson's disease had a greater risk for developing impulse control behaviors.
About a fifth of patients with early Parkinson's disease (PD) had symptoms of impulse control behaviors, and about a quarter of those with symptoms went on to develop full impulse control disorder by about a year later, according to a longitudinal study published in the July 16 online issue of Neurology.
Independent experts said the findings draw attention to the impulse control problems associated with dopamine agonists, which the study found was the most potent single predictor of impulse control disorder.
The paper is based on data from a study that examined the frequency, severity, and progression of impulse control behaviors in early PD through screening followed up by in-depth interviews. The interview details provide a more nuanced look at the topic compared with many previous studies that relied on screening alone, researchers said.
“The interview element of the study allowed us to accurately diagnose impulse control disorders to validated criteria, characterize the severity of the behavior, and collect qualitative data about each case,” said Fahd Baig, DPhil, a clinical research fellow at the Oxford Parkinson's Disease Centre. “We were interested in not just the cases which fulfilled the criteria for an impulse control disorder but also the less severe cases that still exhibited impulse control behaviors, and to investigate how these evolved over time.”
Participants were from an Oxford cohort enrolled in a prospective study of early PD patients—who had been diagnosed within the previous 3.5 years—and were followed longitudinally. A total of 921 patients were screened, and the 194 who screened positive for impulse control behaviors were eligible for an interview. Due to non-responses to invitations, just 88 participated in interviews.
To account for the non-responders, researchers used multiple imputation, in which plausible imputed sets of data are used in place of the missing data to account for the uncertainty of the data that are missing. Using this approach, the prevalence of patients with impulse control disorders was 19.1 percent.
Researchers also found that 24 percent of those who exhibited behaviors not severe enough for a diagnosis of impulse control disorder in their initial interview were in follow-up interviews (at least 12 months later) diagnosed with the disorder. This progression was seen in five of the 21 patients who did follow-up interviews.
“The most immediately applicable finding is evidence to suggest that patients with mild symptoms are at high risk of developing the more severe form of the disorder,” Dr. Baig said. “It is established clinical practice to inquire about these during a patient encounter anyway, but this reinforces the need to elicit even mild symptoms.”
Use of a dopamine agonist was the most potent single predictor of impulse control behaviors, researchers found (adjusted OR = 4.38; p=.003). Apathy measured on the Movement Disorder Society-sponsored Unified Parkinson Disease Rating Scale (MDS-UPDRS) was also a significant predictor, they found (adjusted OR = 2.71; p=.006).
“The association of apathy with an increased risk of ICD is interesting as it is linked with reward insensitivity, which is modulated by dopaminergic medication,” Dr. Baig said.
Researchers said that patients often reported in interviews that their subsyndromal PD-ICD symptoms were a worsening of behaviors that existed before their medication was started, such as comfort eating or heavy internet use. But those with syndromal impulse control behaviors tended to describe a more sudden development of symptoms.
The cases involving syndrome PD-impulse control disorder often described a relatively rapid onset of a behavioral change which the participants described as ‘new’ or ‘out of character’ (such as a change in sexual orientation or a novel gambling habit) following the initiation of a dopamine agonist, the researchers wrote. They noted that this was just an exploratory finding based on qualitative interviews. They were not able to substantiate the presence of subtypes of ICD, but the area deserves future investigation, Dr. Baig said.
Dr. Baig said he hopes the findings encourage clinicians to look to factors beyond dopamine agonist use to help control ICB symptoms.
“Given the well-known difficulty in withdrawing dopamine agonists in a number of patients, it encourages clinicians to also address any modifiable psychosocial factors and promote the engagement of the patient's protective social networks,” he said.
Stephen Grill, MD, PhD, co-founder of the Parkinson's and Movement Disorders Center of Maryland and assistant professor of neurology at Johns Hopkins, said that he has long shied away from prescribing dopamine agonists largely due to concerns about impulse control disorder.
“I haven't initiated anybody on a dopamine agonist in several years,” he said. “The impulse control disorder is a big part of it. I've had horrible cases.”
Dr. Grill said he once had a patient on a dopamine agonist who had lost hundreds of thousands of dollars in gambling as a result of impulse control disorder.
He said that when dopamine agonists first became available, they were marketed as a way to delay use of levodopa early in the disease course, especially in young people, out of fear of dyskinesias and motor complications.
“Looking back at it, it was all pretty much a mistake,” he said. “And I think at this point, most specialists who really think about it realize that there's no real advantage to dopamine agonists.”
The risk of motor complications hasn't been a significant problem in long-term studies and those on levodopa tend to do better than those on dopamine agonists, he said.
“But it's still entrenched and there are a lot of people using dopamine agonists even though the side effect profile is just not as good as levodopa,” he said.
He said that this study “adds to the caution” because it's a fairly large, prospective study with a 14 percent prevalence of ICD, or 19 percent when statistical methods were used to account for missing interview data.
“Even 14 percent—that means one out of seven patients that I would start on a dopamine agonist would have these problems,” he said. “You know, it's not worth it.”
He said the finding of apathy as a risk factor was particularly interesting, adding that he might lower the threshold of apathy that he uses to refer patients for psychological therapy.
“It makes a lot of sense, that they're filling their time with these addictive behaviors because of their apathy,” he said. “I think I'm going to start paying more attention to that.”
About a quarter of subsyndromal patients went to develop the full disorder points to a window of opportunity, he said.
“If my patients on dopamine agonists are experiencing impulse control disorder, then I slowly taper down off the dopamine agonist,” he said, “and depending upon how it's affecting the family or finances, refer [them] to cognitive behavioral therapy or to a psychologist who has experience with this.”
It is sometimes hard to do this because of a withdrawal syndrome, he said.
Howard D. Weiss, MD, FAAN, director of the Parkinson Disease and Movement Disorder programs at LifeBridge Health Brain & Spine Institute and adjunct associate professor of neurology at Johns Hopkins, said the effects of impulse control disorders can be devastating—[leading to] bankruptcy or the ruin of a marriage—and that a black box warning should be required for dopamine agonists.
Dr. Weiss said he doubts that this study's finding on progression of early symptoms into a full disorder will be very relevant in busy, real-life clinical settings, however, because of the difficulty of picking up on these symptoms when patients hide their behaviors.
“Unless this an area of your intense interest, you're just not likely to have the time or the effort,” he said. “Practically speaking, this is not going to happen.”
Dr. Weiss added: “All of these screening tools for impulse control that have been bandied about I think are really not adequate in dealing with situations where there's going to be active deception on the part of the patient. I think the solution is not to use these drugs frivolously.”
But “a very substantial number of neurologists,” he said, “are still using dopamine agonists without realizing this might not be in the patient's best interest.”
Dr. Baig has received travel expenses from Merz to attend a conference. Drs. Grill and Weiss reported no conflicts.