I'm reaching out specifically to those who have lived with Parkinson's disease for over 10 years and have decided to discontinue dopamine agonists (Mirapex, Requip, Neupro) due to severe side effects. I'm a 56-year-old male, diagnosed with PD 11 years ago, and have been on agonists combined with carbidopa/levodopa (C/L) since 2018.
With my neurologist's assistance, I am currently tapering off the Neupro patch (10mg) due to severe impulse control disorders (ICD) over the past year. I'm particularly interested in hearing from those who have experienced dopamine agonist withdrawal syndrome (DAWS), as documented in scientific literature. This syndrome, which can cause anxiety, panic attacks, and phobia, typically resolves within 6-12 months or less, although about 15% of patients find it intolerable and resume dopamine agonists.
I am presently dealing with DAWS. Since May, I have been reducing Neupro by 2mg every 10 days and am now down to 2mg. Although my C/L dosage has been adjusted to compensate, it hasn't significantly alleviated the DAWS symptoms.
I know it's still early, and I need to be patient. My doctor assures me that things will improve. My current neurologist is experienced in tapering off medications, unlike my previous neurologist, who was opposed to the idea and recommended DBS (which I will never consider).
Has anyone successfully discontinued these drugs and managed their condition with monotherapy or a combination of an MAO inhibitor and levodopa? Any suggestions or advice would be greatly appreciated. Despite maintaining good physical shape through regular exercise since my diagnosis, it doesn't seem to be enough.
Thank you
Written by
WittyPD
To view profiles and participate in discussions please or .
"Although my C/L dosage has been adjusted to compensate, it hasn't significantly alleviated the DAWS symptoms".
At a poor level of compensation the levodopa equivalent daily dose should be similar for the two regimen. Better, the timing of the LED should be similar.
Better still, would be to take account of the dopamine receptors that are affected.
" Dopamine functions by acting on DAergic receptors, which are classified as D1-like receptors (D1 and D5) and D2-like receptors (D2, D3 [sic], and D4). 8, 9 Currently, DA receptor agonists are the first choice of treatment for patients with PD, which delays the onset of l -DOPA therapy."
"Rotigotine is a novel non-ergolinic D3/D2/D1 dopamine receptor agonist developed for patch application. Analysis of the receptor profile of rotigotine showed agonistic activity at all dopamine receptor subtypes, with a pronounced preference towards the D3 receptor. The affinity to the D3 receptor is approxiametly 10 – 20 – fold higher than to the D2 receptor and about 100 – fold higher than the D1 receptor. "
To take account of the dopamine receptors that are affected we would have to take account of the difference between the effect of rotigotine versus dopamine:
" In newly developed reporter-gene assays for determination of functional activity, rotigotine behaved as a full agonist at dopamine receptors (rank order: D3 > D2L > D1 = D5 > D4.4) with potencies 2,600 and 53 times higher than dopamine at dopamine D3 and D2L receptors, respectively"
So levodopa therapy is just not going to stimulate the D3 or D2L receptors anywhere near as much as rotigotine. How to deal with that other than by a gradual taper of rotigotine is not apparent.
Just what does the D3 receptor do anyway? From here:
" D3 receptor blockade appears to enhance while D3 receptor agonism [what dopamine agonists do] seems to impair cognitive function, including memory, attention, learning, processing speed, social recognition and executive function independent of age...These findings suggest that D3 receptor blockade may enhance cognitive performance in healthy individuals and treat cognitive dysfunction in individuals with a neuropsychiatric disorder. "
This worries me,Park Bear. I've taken 4mg rotigatine patch for one year now,and tried to come back down to 2mg, because it makes me feel a bit "weird" , though it helps with wear off. I've found it very difficult to cut back due to the effects....not sleeping, pain in back,arms and leg muscles, and some nights RLS . Any suggestions would be welcome, though I'm trying to keep meds level due to finding the B1 sweet spot .
The doctor increased my levodopa to 900mg and added selegiline to achieve total dopamine compensation, but the mechanisms of levodopa and dopamine agonists (DA) are different. Additionally, DAWS symptoms are not motor-related. The motor symptoms are a consequence. And it's true; I experience it myself. When I am calm, levodopa works perfectly; I still have great days and days when I am extremely agitated and practically always OFF with very high anxiety.
Here’s what my neurologist explained to me: What happens when, having Parkinson's, I take dopamine or dopamine agonists? These substances not only go to the region of the substantia nigra, where the substance is deficient, but also to the frontal lobe, where there was no deficiency. And what happens then? The brain is a plastic organ, meaning it can change over time: the increase in dopamine present in the frontal lobe leads to a progressive increase in the number of receptors for dopamine. Unfortunately, the ventral tegmental area does not increase its production; therefore, over the years, the gap between the dopamine produced and the receptors that MUST be saturated in the frontal lobe increases. And the more the drug dose is increased, the more this gap widens. The patient then starts to feel the end of the dose (wearing off) as a sensation of tension and rigidity, a feeling of anxiety. In these cases, the drug dose is generally increased, worsening the situation! After yet another dose increase, it shifts from wearing off to blockages. In fact, when the brain's tolerance limit is exceeded, the patient increasingly feels the end-of-dose effect more quickly, keeps checking the clock, sees that there are 2 hours left until the next dose, gets agitated, and freezes. They freeze because the automatic walking mechanism is altered. 99% of patients do not know about this detrimental effect of the drugs, and the consequent agitation exacerbates the automatic disturbance to the point where the patient is totally unable to find the correct motor sequences to move.
The only solution is the slow and progressive reduction of the drug dose until finding the dose that allows the patient to no longer experience these side effects. This process requires 6 months to 1 year, complete cooperation from the patient, and, above all, the family members. It takes about 6-12 months for the receptors to normalize and for the signs of DAWS to decrease until they disappear.
It's not me saying this; my doctor supports it, and science backs it up. According to a study published in Movement Disorders (movementdisorders.onlinelib..., similar analyses were performed regarding wearing-off and any motor complication (motor blocks, dyskinesias, freezing during the "on" phase, wearing-off, severe behavioral disturbances, hallucinations).
The symptoms of Parkinson's disease include bradykinesia, rigidity, tremor, and impairment (not loss) of proper execution of automatic movements (turning in bed, maintaining posture, and walking). Everything else is medications side effects. Medications are essential and indispensable, but the indiscriminate use/dose by many neurologists is the problem. It's a huge issue that unfortunately will never be effectively addressed.
That study is about dyskinesia and does not mention freezing of gait. Here is a study of freezing of gait: researchgate.net/profile/Sa...
Patients were not taking Parkinson's medication except that some of the study patients were given selegiline: "Fifty-seven patients (7.1%) had freezing of gait at study entry and 193 (26%) of the remaining patients experienced the symptom by the end of the follow-up period. Those with freezing of gait at baseline had significantly more advanced disease than those without the symptom, as measured by total UPDRS and Hoehn and Yahr stage. High baseline risk factors for developing freezing of gait during the follow-up period were the onset of PD with a gait disorder; higher scores of rigidity, postural instability, bradykinesia and speech; and longer disease duration. In contrast, tremor was strongly associated with a decreased risk for freezing of gait. At the end of follow-up, the signs most strongly associated with the freezing phenomenon were gait, balance, and speech disorders, not rigidity or bradykinesia. Deprenyl [selegiline] treatment was strongly associated with a decreased risk for developing freezing of gait; tocopherol had no effect."
I agree with you that over-prescription of dopaminergic medications by neurologists is a problem, and many patients suffer adverse effects as a result. More on that subject by me here:
What do you think of Dr. Sackler Bernstein 's suggestion that CL is causing harm? Are you able to move after cutting your CL dose? Has you CL dose needed increased over time?
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Ropinirole (requip) shortage and discontinuation by GlaxoSmithKline
Withdrawal when trying to reduce Levodopa 
Hypersexuality and impulse control disorders (ICD)
L-Dopa side effects - psychosis
Entacapone causes diarrhea?
