Another reason to avoid them as long as possible...

Nic 57/16

2010/1/12 mschild <[log in to unmask]>

> Reducing Dosage of Parkinson's Drugs Can Cause Symptoms Similar to Those of
> Cocaine Withdrawal
> ScienceDaily (Jan. 11, 2010) — New research has shown that reducing the
> dosage
> of dopamine agonist (DA) drugs, a mainstay treatment for Parkinson's
> disease
> (PD), sometimes causes acute withdrawal symptoms similar to those reported
> by
> cocaine addicts -- including anxiety, panic attacks, depression, sweating,
> nausea, generalized pain, fatigue, dizziness and drug cravings. These
> symptoms
> can be severe, and are not alleviated by other PD medications.
> For the first time, researchers have defined this phenomenon, which they
> call
> dopamine agonist withdrawal syndrome, or DAWS. Led by a physician-scientist
> at
> NewYork-Presbyterian Hospital/Weill Cornell Medical Center, the study is
> reported in the Jan. 11 Archives of Neurology.
> "Like cocaine and methamphetamines, dopamine agonists work by stimulating
> the
> reward pathways in the brain. For this reason, it makes sense that they
> would
> engender similar withdrawal symptoms, particularly in those with high
> cumulative drug exposure," says senior author Dr. Melissa J. Nirenberg,
> associate director of the Parkinson's Disease and Movement Disorders
> Institute
> at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and assistant
> professor of neurology and neuroscience at Weill Cornell Medical College.
> Dopamine agonists are highly effective drugs that are prescribed to many
> Parkinson's patients to avoid side effects of the "gold standard" drug
> L-DOPA,
> particularly abnormal involuntary movements referred to as dyskinesias. (L-
> DOPA was perfected by Dr. George C. Cotzias of Cornell University Medical
> College in the late 1960s; dopamine agonists have been available since the
> 1990s.) DAs are also FDA-approved for treatment of restless legs syndrome,
> and
> used off-label for other conditions such as depression and fibromyalgia. In
> the
> United States, there are currently two DAs on the market -- pramipexole
> (Mirapex®) and ropinirole (Requip®, Requip XL®).
> In recent years, there have been increasing concerns about DA side effects,
> and
> particularly the fact that they can cause uncontrolled, compulsive
> behaviors
> known as impulse control disorders (ICDs). ICDs are reported to occur in
> about
> 14 percent to 17 percent of PD patients who use these drugs, and also occur
> in
> people who use DAs to treat other medical conditions. In 2006, Dr.
> Nirenberg
> published research linking the use of DAs to compulsive eating; others have
> linked the drugs to behaviors such as compulsive gambling, buying,
> hypersexuality and Internet addiction. Patients are often unaware of these
> addictive behaviors, or may not discuss them with physicians because they
> are
> in denial, embarrassed by their symptoms, or unaware that they are a
> medication side effect.
> "Impulse control disorders stemming from use of dopamine agonists can be
> detrimental to a patient's financial, social and physical well-being. Our
> research identifies another concern -- namely that some patients experience
> severe, even intolerable, withdrawal syndromes when their dosage is
> reduced.
> In this context, it's very important that physicians and their patients use
> DAs judiciously, and exercise caution when they are tapered," says Dr.
> Nirenberg.
> Study Design and Findings
> In the current study, Dr. Nirenberg and first author Christina A. Rabinak,
> a
> third-year medical student at Weill Cornell Medical College, performed a
> retrospective analysis of a cohort of 93 people with Parkinson's disease,
> of
> whom 40 received DAs, and 26 tapered a DA for any of a variety of reasons
> --
> most commonly because of ICDs. Among those who tapered a DA, five patients
> (19
> percent) experienced DAWS. Two of the subjects with DAWS recovered fully,
> but
> three of the five were unable to successfully discontinue the drug because
> of
> severe withdrawal symptoms. These three study participants are currently
> living with their ICDs.
> The NewYork-Presbyterian/Weill Cornell researchers made several
> observations
> about DAWS:
> DAWS only occurred in patients with ICDs, and not in those who tapered DAs
> for
> other reasons. However, only one-third of patients with ICDs experienced
> DAWS.
> Withdrawal symptoms were only alleviated by increasing the DA dosage. Other
> treatments, including high doses of L-DOPA, antidepressants, tranquilizers
> and
> psychotherapy, were ineffective.
> DAWS correlated with cumulative exposure to DAs, with the most severe
> symptoms
> occurring in patients with the greatest DA exposure.
> Subjects with DAWS had milder physical disability than those without.
> The Message for Patients & Physicians
> "DAWS has been difficult to identify because its symptoms are 'invisible'
> --
> mainly psychological in nature," says Dr. Nirenberg. In fact, both patients
> and physicians have mistaken DAWS for a mental health condition such as
> anxiety or depression. DAWS has also been misinterpreted as a manifestation
> of
> PD itself, or of wearing off between doses of medication -- something
> disproven
> by the fact that the symptoms are not alleviated by even very high doses of
> L-
> DOPA.
> Dr. Nirenberg recommends that patients "educate themselves about DA side
> effects, involve family members and friends in monitoring their behavior
> for
> possible ICDs, and promptly inform their physicians if they experience ICDs
> or
> DAWS." The authors also provide specific advice for clinicians who use DAs:
> (1)
> avoid prescribing high doses of DAs, (2) closely monitor DA-treated
> patients
> for signs of ICDs, (3) warn patients of the risks of DAWS, (4) taper DAs at
> the first sign of ICDs, and (5) closely monitor patients when tapering DAs,
> particularly those with ICDs. As for future directions, Dr. Nirenberg
> stated
> "the most important unanswered questions are how to reduce the risk of
> DAWS,
> and how to treat DAWS once it occurs."
> The current study was supported by the Parkinson's Disease Foundation.
>
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