Saturday, October 25, 2008

Pathological Gambling Caused by Drugs Used to Treat Parkinson’s Disease: Yet Another Closer Look, Part Three(a)

Welcome to Part Three(a) of a three part series.

To recap the background provided in Part One, in the 2005 study entitled “Pathological Gambling Caused by Drugs Used to Treat Parkinson’s Disease,” the authors mine records of Parkinson’s patients seen at the Mayo Clinic in Rochester, MN (MCR), between 2002 and 2004, and find 11 people who had developed pathological gambling (PG) - they conclude that the PG was caused by Parkinson's drugs. The authors so completely fail to provide evidence compelling enough to support this conclusion that the fact that this study was published in a peer-reviewed journal boggles the mind. It is available online for free at the Archives of Neurology, if you are interested. It may actually be necessary to read the study for what I am about to say to make sense – I don’t know.

According to the authors of this study, the 11 people who gambled fit the DSM-IV-TR criteria for PG.* They also say that the PG was temporally associated with the commencement, increase, and/or cessation of dopamine agonist (DA) therapy, a type of drug used to treat Parkinson’s disease (PD), and, for a disproportionate percentage of these people, the culprit was a DA called pramipexole.

Finally, the authors provide the results of their survey of the field of literature, and present in a table six studies in support of their conclusion that Parkinson’s drugs cause – not just “are associated with,” but cause PG.

In Part One, I addressed the authors’ failure to adequately support their central assertion, that DAs cause PG, in the context of what criteria must be met to identify a causal relationship. In Part Two, I addressed specifically the authors’ failure to provide any indication of the prevalence of this phenomenon and show how that pretty much single handedly invalidates the study. And in Part Three(a), I will address the authors’ failure to delineate the parameters of what they call a temporal relationship, and question the resultant inclusion of two of the 11 PGers.

I apologize for the enormous gaps between my posts but I write these things at night, and my meds are only carrying me through the work day in terms of typing. So, I may have to finish Dodd in more bite-sized bits.

Dodd et. al. base their assertion that there is a causal association between dopamine agonist (DA) therapy and pathological gambling (PG) on the presence of what they call a temporal relationship. A temporal relationship exists when Outcome Y follows the introduction of Variable X within a period of time that is considered plausible for a connection. Plausibility is determined by the natures of variable and the outcome – for example, if Outcome Y is deemed to be an allergic reaction and Variable X is a bee sting, the plausibility of their being related remains intact for a far shorter period of time than if Outcome Y is lung cancer and Variable X is smoking.

It should come as no surprise at this point that Dodd et. al. fail to delineate the parameters they use to identify the purported temporal relationship between DA therapy and PG. If we are curious, however, we should be able to infer them from the data provided, which is summarized in the table below:

With the help of common sense, it would seem reasonable to me to infer from the above that as long as either the latency of DA therapy initiation to gambling addiction (3rd column) or the latency of the discontinuation of DA therapy to the resolution of gambling (4th column) is less than or equal to 3months, the authors consider the possibility of a temporal relationship to be plausible – well, for most of the patients listed, anyway.

Patients 8 and 10 are different.

For Patient 10, even if we disregard the 2.5 year latency to PG onset, the authors ask us to stretch plausibility a minimum of 3 months in considering a latency to cessation of PG of up to 6 months after discontinuing DA therapy.

And – I am just going to say it – the inclusion of Patient 8, with her year-long latency to onset and the fact that they have no evidence that she ever stopped, is ludicrous.

And that brings the total number of people found to have started PG while taking PD meds down from 11 to 9, for whatever that is worth.

I think I will wrap up with a summary of what the studies Dodd et. al. cite in support of their conclusion really say but that will have to wait for another day.

* Pathological gambling is defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DMS-IV-TR) as follows, and the study does not describe in which five each patient has engaged:

A. Persistent and recurrent maladaptive gambling behavior as indicated by five (or more) of the following:
  1. is preoccupied with gambling (e.g., preoccupied with reliving past gambling experiences, handicapping or planning the next venture, or thinking of ways to get money with which to gamble)
  2. needs to gamble with increasing amounts of money in order to achieve the desired excitement
  3. has repeated unsuccessful efforts to control, cut back, or stop gambling
  4. is restless or irritable when attempting to cut down or stop gambling
  5. gambles as a way of escaping from problems or of relieving a dysphoric mood (e.g., feelings of helplessness, guilt, anxiety, depression)
  6. after losing money gambling, often returns another day to get even ("chasing" one's losses)
  7. lies to family members, therapist, or others to conceal the extent of involvement with gambling
  8. has committed illegal acts such as forgery, fraud, theft, or embezzlement to finance gambling
  9. has jeopardized or lost a significant relationship, job, or educational or career opportunity because of gambling
  10. relies on others to provide money to relieve a desperate financial situation caused by gambling

B. The gambling behavior is not better accounted for by a manic episode

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