By Steven DiJoseph
As previously reported by newsinferno.com, the medical evidence has been mounting with respect to the rather odd connection between certain drugs used to treat ParkinsonÃ¢â‚¬â„¢s disease (PD), especially Mirapex, and the development of compulsive behavior including pathological gambling.
Last July, a Mayo Clinic study published in the Archives of Neurology that identified 11 ParkinsonÃ¢â‚¬â„¢s patients who developed a gambling habit while taking Mirapex or similar drugs between 2002 and 2004. After the study was released, 14 additional Mayo patients were diagnosed with the problem according to lead author Dr. M Leann Dodd, a psychiatrist at the Clinic.
Previously, in August 2003 in the journal Neurology, Drs. E. Driver-Dunckley, J. Samanta, and M. Stacey published an article entitled Ã¢â‚¬Å“Pathological gambling associated with dopamine agonist therapy in ParkinsonÃ¢â‚¬â„¢s disease.Ã¢â‚¬Â
That study found extreme cases of compulsive gambling in nine (of 1,884) patients using pramipexole (8 or 1.5%)) and pergolide (1 or 0.3%). Both results were well above the overall incidence rate of all PD patients of 0.05%. Both drugs that showed an increased risk were dopamine agonists (DA).
The Mayo Clinic study also analyzed the findings in five prior studies (including the 2003 Driver-Dunckley study) and confirmed that: Ã¢â‚¬Å“All of the commonly prescribed dopamine agonists have been associated with pathological gamblingÃ¢â‚¬Â with pramipexole being Ã¢â‚¬Å“disproportionately represented in both our series (82% of our patients) and in prior reports (59%).Ã¢â‚¬Â
Mirapex (pramipexole dihydrochloride) is in the dopamine agonist class of drugs and is believed to work by mimicking the action of dopamine in the brain to help control the symptoms of ParkinsonÃ¢â‚¬â„¢s disease.
Dopamine also affects brain processes that control emotional responses and a person’s ability to experience pleasure and pain. It is thought to play a role in addictive behavior.
Unfortunately, this is another drug whose benefits come with a very high price tag for some patients. The ones who become addicted to gambling often wind up losing their life savings, fall deeply into debt, and even jeopardize or destroy their marriages or other personal or family relationships.
In the past, the victims of this harsh side-effect had no idea what had come over them. Their brain was literally taken over and their gambling became constant and compulsive. Simply stated, they were out of control and had no idea why. For these people, the situation was frightening and inexplicable.
As a result of this completely bizarre and damaging side-effect, many Mirapex users suffered long periods of debilitating and destructive behavior during which they were unaware that the drug was causing the problem and that it would cease if they discontinued taking it.
Mirapex is manufactured by German-based Boehringer Ingelheim Pharmaceuticals, the world’s biggest family-owned drug company, in cooperation with New York-based Pfizer, the world’s largest drugmaker. Its sales for 2004 topped $200 million in the U.S. alone.
.Boehringer Ingelheim lists “compulsive behaviors (including sexual and pathological gambling)” as a possible side effect associated with taking Mirapex. That seven-word phrase on page 17 of a 21-page highly technical document is all the warning that is given concerning the potentially detrimental side-effect.
While Boehringer-Ingelheim has repeatedly claimed there is no scientific evidence upon which to base the conclusion that Mirapex causes addictive or compulsive behavior, the multiple reputable studies on the subject would seem to indicate otherwise. In addition, the company revised its package insert to include the warning with respect to Ã¢â‚¬Å“compulsive behaviorÃ¢â‚¬Â despite its denial of the connection.
Now, additional evidence of the association between Mirapex and other dopamine agonists and impulsive behavior has appeared in the form of an analysis of adverse drug reports in the FDAÃ¢â‚¬â„¢s database. Of the reports specifically dealing with compulsive gambling, 39 (58%) involved Mirapex.
The report, which analyzes these adverse events, appears in the February issue of Archives of Neurology. The authors include a psychiatrist, P. Murali Doraiswamy (Duke University), and three FDA scientists.
According to Dr. Doraiswamy: “When you combine this with other pieces of evidence, it seems highly suggestive that there is a causal relationship.”
While the evidence is consistent with other findings linking dopamine agonists with an increased risk of impulsive behavior, the researchers claim to have found no similar reports involving antipsychotic drugs, which inhibit dopamine.
Boehringer Ingelheim has now backed off its hard line denial of a link just a bit by stating that it is working with ParkinsonÃ¢â‚¬â„¢s experts to Ã¢â‚¬Å“investigate the relationship if any.Ã¢â‚¬Â
The behavioral changes witnessed in some ParkinsonÃ¢â‚¬â„¢s patients whose therapy includes dopamine agonists can be wide-ranging indeed. On the mild side, some start buying lottery tickets and nothing more. Others, however, have been known to develop serious OCD (obsessive compulsive disorders) as well as aggressive sexual impulses, overeating, medication abuse, or pathological gambling.
Since these personality changes are dramatic and involve conduct that the patient has usually not exhibited in the past, relatives and associates should be aware of the potential problem and remain watchful for marked behavioral changes.
PD causes sufferers to gradually lose dopamine. Thus, they actually develop an aversion to the type of impulsive behavior associated with excess dopamine. When Mirapex, Requip, or another dopamine agonist is introduced, the behavioral changes in those adversely affected can be both quick and dramatic.
Currently, two major lawsuits against Boehringer Ingelheim and Pfizer have been commenced in federal court in California and in Superior Court in Ontario, Canada. They allege a number of addictive behaviors associated with Mirapex including gambling, shopping, having sex, eating, and engaging in other compulsive conduct.
It is likely that additional lawsuits will be commenced in the near future since the problem is as widespread as the locations of people who took Mirapex.
Jerrold Parker, managing partner of Parker & Waichman, a law firm with considerable experience in pharmaceutical and medical malpractice litigation nationwide, told us after the release of the Mayo Clinic study that: Ã¢â‚¬Å“It is difficult to imagine how the manufacturers of Mirapex can maintain there is no scientific evidence to support the addiction link when several studies leave little doubt of the connection. In addition, it is rather amazing that when the manufacturers finally decided to add a warning regarding compulsive conduct to the product insert they chose to hide it in the middle of 21 pages of technical data.Ã¢â‚¬Â
When asked to comment on the most recent research report, Mr. Parker stated: Ã¢â‚¬Å“The evidence is only growing stronger. The link between Mirapex, and the dopamine agonist class of drugs, and an increased risk of dangerous compulsive behavior is really undeniable. Only a radically conservative scientist and the drugÃ¢â‚¬â„¢s manufacturer would still need more proof that a serious problem exists.Ã¢â‚¬Â