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Reduction of Dopamine Agonists May Lead to Withdrawal Symptoms

Reducing the dosage of dopamine agonists in people with Parkinson’s disease (PD) may produce withdrawal symptoms, such as dizziness, anxiety and panic attacks, according to a report in the January issue of Archives of Neurology.

Melissa J. Nirenberg, M.D., Ph.D., and her colleague Christina A. Rabinak, of New York-Presbyterian Hospital/Weill Cornell Medical Center, studied the effects of dopamine agonists, a class of PD medications that includes pramipexole (Mirapex®) and ropinirole (Requip®).

Dr. Nirenberg performed a retrospective study examining the medical records of 93 people living with PD, 40 of whom had received dopamine agonists and 53 of whom had been treated with other medications.  The participants were similar with regard to age, disease duration, gender and age of Parkinson’s diagnosis.

She and her colleague found that during routine Parkinson’s care, the dopamine agonist dosages of 26 people within the group had been reduced by their doctors.  This “tapering-off” was often performed because the person was experiencing an impulse control disorder, such as pathological gambling, compulsive eating and compulsive shopping — which can be side effects of the medications.

Following the reduction in medication dosage, five people developed persistent anxiety, panic attacks, depression, orthostatic hypotension (low blood pressure), fatigue, pain and drug cravings.  Dr. Nirenberg has named this phenomenon as dopamine agonist withdrawal syndrome, or DAWS.  The syndrome tended to develop immediately following drug tapering, which resembles the course of withdrawal symptoms in most situations of drug dependence or addiction.  In addition, the individuals who experienced DAWS had all previously experienced an impulse control disorder, such as a gambling addiction, hypersexuality or excessive spending.  Individuals with DAWS requested to resume their prior high dose of dopamine agonists, even though their PD motor symptoms were well controlled.

The reward and pleasure systems of the brain use the neurotransmitter dopamine.  Impulsive, addictive behaviors have been associated with the dopamine drugs used in Parkinson’s.  Some people with PD take excessive amounts of dopamine agonists in order to alleviate anxiety and unpleasant sensations that occur when their medications wear off.

This study reveals another consequence of dopamine agonist dependence in people with PD: a prolonged unpleasant withdrawal state that is not easily relieved.  The study involved a small number of people, and more research is required to learn about incidence, risk factors, time course and pharmacological aspects of DAWS, as well as strategies to avoid or treat the syndrome.  For people with PD and physicians who plan to reduce dopamine agonists, it is important to be aware that symptoms of withdrawal can occur, especially in individuals with a history of anxiety and addictive behaviors.

This study was conducted with funding from PDF through its Center Grant to Weill Cornell Medical Center.

To learn more about currently available medications for Parkinson's, visit http://www.pdf.org/en/meds_treatments.

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A Genetic Mutation Provides Clues for the Expression of PD

For some of the people who experience Parkinson’s disease (PD) before the age of 50 and who carry a genetic mutation in a gene named LRRK2, it appears that gait and balance difficulties are more common than tremor.  These findings were reported in the December 2009 issue of Archives of Neurology.  Although genetic mutations like LRRK2 account for only a small percentage of cases of Parkinson’s, scientists hope that these few cases will open a window into the cause(s) of the disease.  It is speculated that understanding the roles of genes in PD will help predict its symptoms and progression. 

The authors, led by Roy N. Alcalay, M.D., and Karen Marder, M.D., M.P.H., of Columbia University, gathered data on 925 people living with early-onset Parkinson’s (those who developed PD before the age of 51) — all of whom were recruited from 13 movement disorder centers that constitute the Consortium on Risk for Early-Onset Parkinson’s Disease (CORE-PD).  Studying early-onset PD is especially useful in research because these individuals are more likely to have a familial form of PD.

Using a neurological examination to rate each person’s PD symptoms, according to the standardized Unified Parkinson’s Disease Rating Scale (UPDRS), the investigators classified people into two groups: individuals with mainly a tremor of the arm or leg and individuals with a predominance of gait and balance problems.  On average, the clinical assessments were done at the ten-year point in the development of PD.  All of the people involved in the study had donated blood for genetic testing, and the researchers detected the most common known mutation — the G2019S mutation in the LRRK2 gene — in 34 of the 925 people (or 3.7 percent).

It turned out that nearly all of the 34 carriers of the G2019S mutation experienced balance and gait problems as the main signs of their PD.  The researchers further noted that these problems were not the result of longer disease duration in the people with PD with the genetic mutation, even though in previous studies, scientists had linked balance and gait problems to more severe disease progression.

In the long run, careful studies of genetic mutations that examine the way in which the disease presents itself may help researchers understand what type of PD a person has and how best to treat it. 

This study was supported by PDF’s Center grant to Columbia University.

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For the latest Parkinson’s science news, visit www.pdf.org/en/science_news.