Reduction in Parkinson’s Medications Tied to Withdrawal Syndrome

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 agonist 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 the Center Grant to Weill Cornell Medical Center.