Medication Change May Improve Impulse-Control Disorder in Parkinson's

November 22, 2018

By Will Boggs MD

NEW YORK (Reuters Health) - Impulse-control disorder (ICD) behaviors in patients with Parkinson's disease (PD) appear to improve after switching from dopamine agonist to levodopa/carbidopa slow-release formulations, researchers from South Korea report.

About 15% of patients with PD develop ICD, with a higher risk in patients using immediate-release or oral formulations of dopamine agonists. The first option for management is to reduce the doses of dopamine agonist or switch to levodopa, but evidence supporting improvement of a particular trait is lacking.

Dr. Jinwhan Cho from Sungkyunkwan University School of Medicine, in Seoul, and colleagues in the REIN-PD trial tested whether aberrant behaviors and personality traits in PD patients with ICD are influenced by replacing dopamine agonists with levodopa/carbidopa slow-release formulations in 50 PD patients with ICD, 60 PD patients without ICD and 40 drug-naive patients newly diagnosed with PD.

At baseline, PD patients with ICD had higher modified Minnesota Impulsive Disorders Interview (mMIDI) scores, higher Neuropsychiatric Inventory total and distress scores, and higher frequency of neuropsychiatric ailments, compared with the other two groups of PD patients.

After 12 weeks of intervention with levodopa substitution, mMIDI scores improved significantly, by an average 5.27 points, in the PD-ICD group, the researchers report in the Journal of Neurology, Neurosurgery and Psychiatry, online October 26.

Improvement in mMIDI scores was greatest in hypersexual behaviors, followed by compulsive eating, compulsive repetitive behaviors, gambling and shopping.

The modified regimen also improved patients' activities of daily living when it was successfully implemented, the researchers note.

Despite overall group improvements in mMIDI scores, four patients showed paradoxical worsening of mMIDI scores after 12 weeks of intervention.

Two (5.3%) of the 38 patients in whom dopamine agonists were completely replaced with levodopa/carbidopa developed dopamine-agonist withdrawal syndrome (DAWS), and another two showed aggravation of parkinsonism. All four patients dropped out of the study.

"The results provide class IV evidence suggesting that a successful substitution of dopamine agonists by levodopa controlled ICD behaviors and improved patients' activities of daily living but without affecting individual neuropsychiatric traits," the researchers conclude.

"A long-term follow-up study is needed to demonstrate the long-term prognosis following a switch from dopamine agonists to levodopa in PD patients with ICD and to define a safe strategy to prevent DAWS in patients undergoing replacement therapy or reducing their dose of dopamine agonists," they add.

Dr. Juan Carlos Martinez-Castrillo from Hospital Ramon y Cajal, in Madrid, Spain, who wrote a accompanying editorial, told Reuters Health by email, "This study confirms something we already anticipated: the difficulty in treating ICD once it has been established. The main strategy is slow tapering of dopamine agonists to prevent apathy, an unusual but severe dopamine-agonist withdrawal syndrome. ICD may take months to disappear, and if still severe, a personalized approach should be done."

"The essential idea would be prevention," he said. "Treatment with dopamine agonists should be avoided whenever possible, and certainly in case of prescribing them, maintain a high index of suspicion always at each follow-up visit."

Dr. Gregory Pontone, director of Parkinson's Neuropsychiatry Clinical Programs at Johns Hopkins School of Medicine, in Baltimore, Maryland, told Reuters Health by email, "Although these disorders are collectively called 'impulse control' disorders, it is likely that they are mechanistically different. For example, maybe some are disorders of 'reward weighting' such that behaviors, like compulsive sexual behavior, become overvalued. Behaviors like compulsive gambling may be more an issue of addiction and are likely to be more self-sustaining even after the agonists are removed."

"I think one of the clinical messages is that impulse-control disorders may need different treatment approaches," he said. "For example, compulsive sexual behaviors may be more likely to remit by simply stopping dopamine agonists, while compulsive gambling may require additional measures, such as 12-step groups."

Dr. Cho did not respond to a request for comments.


J Neurol Neurosurg Psychiatry 2018.

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