Scientific Studies of Mirapex and Dopamine Agonists
I have now caught up to the present in my story.I will not have to use italics for writing about events as they are happening to distinguish them from my back story, but I will keep the convention of starting each entry with a date. In this and following chapters I will reserve italics for quotes from documents or other people.
The way we feel, how we think, what makes us human is made possible by neurons; cells of the nervous system.Neurons transmit the signals that move our muscles, signals that make us cry and signals that can turn us into serial killers.Neurons can transmit signals between other neurons by electrical and chemical signals.Electrical signals jumping between neurons are primarily how we move our muscles.Chemical transmission is how we feel.
Neurotransmitters are the chemicals that are released by a neuron and are then taken up by the adjoining neuron in locations called receptors.Science has identified over 100 neurotransmitters.Two of the most well known of these are endorphins and dopamine.The body releases endorphins in response to fear or trauma.Endorphins act as the body’s pain killers.Dopamine is associated with thought and pleasurable feelings.Drugs or disease can interfere with the receptors and neurotransmitters with both beneficial and catastrophic results.
Most people have had firsthand experience with receptors in the brain and drugs; specifically caffeine.My first cup of coffee had an enormous effect on how I felt.As I kept drinking coffee, that effect lessened.Soon I needed more coffee to get the same effect.My brain was working to return to “normal” by adjusting the receptors to account for the increased levels of caffeine.Thankfully coffee is easily obtained and is not illegal so most of us do not have to go through caffeine withdrawal where the brain has to re-adjust to no caffeine.
Dopamine agonists are drugs that can activate dopamine receptors in the brain without needing the body’s produced dopamine.Diseases that are associated with a natural lack of dopamine such as Parkinson’s are treated with dopamine agonists.Restless leg syndrome is also treated with dopamine agonists.Mirapex (Pramipexole) is a dopamine agonist.Requip (Ropinirole) is another.
Several unbiased published scientific studies have investigated the link between dopamine agonists and compulsive behaviors.One such study was presented at the 12th International Congress of Parkinson’s Disease and Movement Disorders held in Chicago in June 2008.It was subsequently published in the Archives of Neurology in the May 2010 issue titled “Impulse Control Disorders in Parkinson’s disease: a Cross-sectional Study of 3090 Patients” by Weintraub et al.A total of 3090 Parkinson patients were surveyed in the study.It was found that impulse control disorders (compulsive behaviors) were common in patients taking dopamine agonists.Only 6.9% of the patients not taking a dopamine agonist had an impulsive control disorder.However, it was found that 17.1% of patients that were taking a dopamine agonist had an impulse control behavior.
The Weintraub study only surveyed four compulsive disorders; compulsive gambling, compulsive eating, compulsive sexual behavior and compulsive buying.These specific disorders were picked as they have established criteria for diagnoses.Accordingly, the study does not rule out the presence of other compulsive behaviors associated with dopamine agonists.
The article “Impulsive Smoking in a Patient with Parkinson’s Disease Treated with DopamineAgonists” by Bienfeit et al., published in the Journal of Clinical Neuroscience in April of 2010, details the compulsive behavior of a patient taking a dopamine agonist.They describe a patient with Parkinson’s disease who developed an unusual manifestation of impulsive behaviors, including cigarette smoking, associated with an increase in dopamine agonist medication. They attributed this behavior to an overstimulation of mesolimbic dopamine receptors responsible for reward-seeking behaviors.There are several dopamine systems in the brain, but the mesolimbic is associated with motivation and addictions.
Yet another more recent article published in the July 2011 journal Physiology and Behavior is worthy of having the whole abstract repeated here.The article is titled “Pathological Behaviors Provoked by Dopamine Agonist Therapy of Parkinson’s Disease” by J. E. Ahlskog .Here is the complete unaltered abstract.
“The dopamine agonist medications, pramipexole and ropinirole, are commonly used to treat Parkinson’s disease. These two drugs have a highly specific affinity for cerebral D3 receptors, known to be localized to the mesolimbic system. Herein is described a common side effect of these drugs, encountered in our routine clinical practice: pathological behaviors. This includes excessive gambling, hypersexuality, shopping, hyperphagia or obsessive hobbying, which may develop in up to 30% of people taking higher agonist doses. In contrast, treatment with the dopamine precursor, levodopa, in the absence of D3 agonist therapy very rarely provokes such behavioral syndromes. Although these agonist-induced behaviors have been called “impulse control disorders”, the problem is not simply loss of impulse control, but rather a novel obsessive-compulsion directed at one or a few behaviors, often taking on pathological proportions. This experience points to the dopamine D3 receptor as a potential therapeutic target for gambling, sex or other addictions occurring spontaneously in the general population.”
Levodopa is commonly used in the treatment of Parkinson’s disease, but it is not a dopamine agonist.Cerebral D3 receptors are dopamine receptors in the brain that play an important role in reinforcement and reward.Mirapex and other dopamine agonists have unique and selective affinity for dopamine D3 receptors. This abstract clearly describes Mary’s behavior in “clinical” terms as well as the behavior of the other victims who have e-mailed me in response to my video on YouTube.
All of these more recent articles give tremendous weight to the original ground breaking Mayo clinic study involving 267 patients treated between 2004 and 2006 in a seven-county area around the Mayo Clinic. The study was published in April 2009 issue of the Mayo Clinic Proceedings.The article “Frequency of New-Onset Pathologic Compulsive Gambling or Hypersexuality After Drug Treatment of Idiopathic Parkinson Disease “is by Bostwick et al.Of the 267 patients 38 were using doses of a dopamine agonist in the therapeutic range (greater or equal to 2 mg/day).
Seven of the patients taking dopamine agonists at the therapeutic range developed a new gambling and or hyper sexuality compulsive behaviors (an occurrence rate of 18.4 percent for this group).In five of these patients the compulsive behaviors were pathologic and disabling.Other compulsive behaviors were noted as well in those seven patients. They were compulsive lawn care, compulsive food and alcohol consumption and compulsive hobby work. The Mayo Clinic researchers found that the compulsive behaviors abated when the patients stopped dopamine agonist therapy.
None of these behaviors were seen in the patients not taking a dopamine agonist, or those taking less than a therapeutic dose of a dopamine agonist, or patients receiving treatment with carbidopa/levodopa alone, the researchers said.Importantly the researchers noted that because this is a retrospective study, cases may have been missed, and hence this study may reflect an underestimation of the true frequency of compulsive behaviors.
Even scarier results from this 2004-2006 study documented that two of the patients had severe enough problems to require extensive treatment for what were at first considered a primary psychiatric problems.Only later was the dopamine agonist cause recognized.My daughter Mary’s experience was the same.Mary’s psychiatrist felt that Mary also had primary psychiatric problems and at the time did not realize the cause was the dopamine agonist Mirapex.Another of Mary’s doctors also erroneously diagnosed her with bi-polar syndrome, a disorder she had never shown any symptoms for prior to or after taking Mirapex.
Thanks to the responses I have gotten from the video I posted on YouTube I was able to also tabulate the frequency and type of compulsive behaviors.The percentages I show will certainly change as the number of responses increases.However, my purpose is not to calculate exact percentages, but to bring to light the varied compulsive behaviors caused by taking a dopamine agonist, specifically Mirapex.The compulsive behaviors reported to me, in order of the highest percentage were:compulsive gambling, 31%; compulsive shopping, 17%; compulsive eating, 14%; compulsive sewing, 6%; compulsive sexuality, 4%; compulsive dumpster diving, 4%; compulsive chocolate craving,4%; compulsive smoking, 4%; compulsion to finish tasks, 4%; compulsion to start multiple new businesses, 4%; compulsive lying, 4% , and compulsive tinkering 4%.These percentages are in line with the gross observations of other researchers in that the most highly reported compulsive behavior is compulsive gambling.Most responders had more than one of these compulsive behaviors.
All of these varied behaviors were extremely disabling to the victims that took Mirapex.The conclusion from my study is that Mirapex (dopamine agonist) caused compulsive behaviors are as varied as the people that fall victim to dopamine agonists and most likely reflect behaviors specific to the individual’s likes and dislikes.
These studies I have so far described have thoughtfully and carefully correlated the use of dopamine agonists to the onset of compulsive behaviors.These studies have surmised how the dopamine agonists can stimulate the “pleasure centers” of the brain driving the victims into unwanted and uncontrolled destructive behavior.Importantly a newly published study establishes a direct link to dopamine agonists and changes in the brain. This study,”Dopamine Agonists and Risk: Impulse Control Disorders in Parkinson’s Disease” by Voon et. al. (May 2011, Oxford journal Brain) now has positively shown that dopamine agonists physically alter the brain’s reaction to risk.The study uses functional magnetic resonance imaging to “see” the responses in the brain as the subjects underwent risk taking choices.
They found that in patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk taking along with decreased activity in the ventral striatal (one of the central areas of the brain’s reward system). Apparently dopamine agonists change sensitivity to risk in patients with impulse control disorder by impairing risk evaluation in the striatum. Their results provide an explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals. This helps explain why Mary was so complacent about losing her well paying business and anxious to embark on a new, but very risky venture of starting a flower business.
Another severe problem that users of Mirapex and other dopamine agonists may experience is DAWS or Dopamine Agonist Withdrawal Syndrome.Patients tapering off of dopamine agonists because of unwanted compulsive behavior, can experience anxiety, panic attacks, agoraphobia (anxiety in situations where it is perceived to be difficult or embarrassing to escape), depression, dysphoria (sudden feelings of sadness, sorrow and anguish), diaphoresis (excessive sweating), fatigue, pain, orthostatic hypotension (lightheadedness from standing up) , and drug cravings.A study “Dopamine Agonist Withdrawal Syndrome in Parkinson Disease” by Rabinak and Nirenberg, published in the Archives of Neurology in 2010, documents these effects.
In this study of 40 subjects that were treated with a dopamine agonist, 26 patients subsequently tapered off of the drugs.Of those 26 patients a total of 19% experienced DAWS.All the patients that experienced DAWS had compulsive behaviors from taking the dopamine agonist.A quote by one of the authors of this study, Dr. Nirenberg is very telling: “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 [dopamine agonists] judiciously, and exercise caution when they are tapered”.
Dopamine withdrawal syndrome is problematic in that it is often unrecognized and is attributed to a mental health condition such as depression and anxiety.This false diagnoses leads to ineffective treatments of the symptoms.The symptoms readily disappear when the patient is put back on the dopamine agonist, but this leads to the resumption of compulsive behaviors.Unfortunately, two of the patients in their study were unable to tolerate the withdrawal process and had to return to their compulsive behaviors.
Most of these studies that I have described have involved Parkinson’s patients.That is understandable since Parkinson patients are most likely to have received therapeutic doses of dopamine agonists.It is very important to note that Parkinson’s disease is not the cause of compulsive behaviors, but that the well documented cause is the treatment of Parkinson’s with dopamine agonists.
All drugs have side effects associated with them, although the percent of serious side effects that cause devastation in a patient’s life are normally very, very low.If this were not true then a drug would be too dangerous to take except in the most necessary cases.It is appalling that Mirapex is in a class of drugs that in the latest research are estimated to cause pathological behaviors (excessive compulsive behaviors) in over 30% of the users.I can only imagine the uproar that would be caused if the word “death” was substituted for “compulsive behaviors”.If over 30% of the users of Mirapex had “died”, the use of Mirapex would have been stopped cold.
The total financial and emotional devastation that Mirapex has caused on the victims that have e-mailed me their stories and the ones documented in these scientific studies are in some ways worse than outright death.At least outright death does not carry the extreme weight of shame and guilt unjustifiably felt by Mirapex victims and the victim is mourned instead of having to suffer a living hell.
May 3, 2012: We are now in the throes of trying to figure out what to do about the rotted and leaking roof on Mary and Joe’s home.We hate to waste the money, money we do not have anyway, to replace the roof if a settlement makes it possible to rebuild a larger structure on top of the new foundation and basement.However mold is forming on the ceiling of the bathroom and in and behind the kitchen cupboards.Something has to be done, but what?
Mary had just confided to me yesterday on the drive into work at the flower shop that during the first year after having stopped taking Mirapex she continually fantasized about the end of the world happening.I admitted I was doing the same thing.I suppose that way we could relieve our anguish without leaving loved ones to mourn us. That period is behind us.
The defendants have all the time and money on their side.I try to put myself into the mindset of the defendants to understand what they are thinking.To do that, I have to rid my mind of any shred of humanity, fairness, justice and empathetic feeling and focus on a goal of getting the smallest settlement possible regardless of the merits of the lawsuit.In that state of mind it is easy to understand why they are acting as they have.By parsing out ridiculously small offers they are trying to reset how we are viewing a fair settlement.We have all experienced this “reset” in expectations.An extreme example is of someone that loses a limb.At first they are depressed over the loss and focus on how their life has changed for the worse.However, within a year or two most will report being as happy as they were before they lost a limb. The defendants have honed their techniques over many lawsuits.They are in no hurry to settle.Time is on their side.
I fear they will squash all of us like bugs as the pressure becomes too much to bear.