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 will address the central assertion, that DAs cause PG, in the context of identifying a causal relationship. In Part Two, I will address the significance of prevalence in that endeavor. And in Part Three, I will address several other questions that come up when one actually reads the study rather than the press coverage it received.
I am probably not telling you anything new when I say that researchers, or responsible ones, at least, can’t just declare that X causes Y, they have to – or are supposed to - prove it, or at least put forth compelling supporting evidence.
Nor can they themselves willy-nilly decide what is compelling and what isn’t – while there is some leeway, there are certain gauges that are accepted as valid, and the degree to which their evidence measures up on those gauges determines its persuasiveness.
One such gauge is Naranjo’s algorithm, which consists of a series of questions to which each possible answer (yes/no/unknown) is assigned a different number of points, thereby weighting the each answer according to its significance. In the end, the total number of points indicates how compelling the evidence is. Below is how this particular study fares using Naranjo’s algorithm:
As you can see, the evidence provided in this study is not compelling enough to indicate even a probable association, never mind definite, or causal, association.
Another set of guidelines can be found on the World Health Organization’s web site – following each bullet point below are my comments on how compellingly the evidence presented in this study fulfills these criteria:
Clearly, the evidence presented In this study, as evaluated by two widely respected and utilized measures, is not nearly compelling enough to support the conclusion that there is a causal relationship between DAs and PG. But if that doesn’t convince you, read on to Part Two. ****** * 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:
Building on the seminal work on determining causality of the Surgeon General’s Advisory Committee on Smoking and Health (1964),3 the generally established criteria underpinning vaccine [or, in this case, drug] adverse event causality assessment that the GACVS uses may be summarized as follows:
- Consistency. The association of a purported adverse event with the administration of a [drug] should be consistent, i.e. the findings should be replicable in different localities, by different investigators not unduly influencing one another, and by different methods of investigation, all leading to the same conclusion(s).
This study was preceded by a single other study which claimed to have found the same association. Even if that single study had adequately supported its conclusion (which it did not), it would obviously fail to provide what could be called consistency of any sort.
- Strength of the association. The association should be strong in the magnitude of the association (in an epidemiological sense), and in the dose-response relationship of the [drug] with the adverse effect.
The authors do not provide the information necessary to evaluate the magnitude of the association, i.e. prevalence – see Part Two.
- Specificity. The association should be distinctive ñ the adverse event should be linked uniquely or specifically with the [drug] concerned, rather than its occurring frequently, spontaneously or commonly in association with other external stimuli or conditions.
PG occurs frequently, spontaneously, and commonly in association with other external stimuli or conditions, like depression and disability.
- Temporal relation. There should be a clear temporal relationship between the [drug] and the adverse event, in that receipt of the [drug] should precede the earliest manifestation of the event or a clear exacerbation of an ongoing condition. For example, an anaphylactic reaction seconds or minutes following immunization would be strongly suggestive of causality; such a reaction several weeks after vaccination would be less plausible evidence of a causal relation.
The authors neglect to define any parameters for identifying a temporal association, and indeed inclusion of three of the eleven on that basis stretches the bounds of plausibility past the breaking point.
- Biological plausibility. The association should be coherent; that is, plausible and explicable biologically according to known facts in the natural history and biology of the disease.
There are those who point to the role of dopamine in addiction, but there are serious questions that remain not only unanswered, but unasked. For example, if one’s medication is maintaining an appropriate level of dopamine in the brain, why would one be any more vulnerable to addiction than anyone else?
- 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)
- needs to gamble with increasing amounts of money in order to achieve the desired excitement
- has repeated unsuccessful efforts to control, cut back, or stop gambling
- is restless or irritable when attempting to cut down or stop gambling
- gambles as a way of escaping from problems or of relieving a dysphoric mood (e.g., feelings of helplessness, guilt, anxiety, depression)
- after losing money gambling, often returns another day to get even ("chasing" one's losses)
- lies to family members, therapist, or others to conceal the extent of involvement with gambling
- has committed illegal acts such as forgery, fraud, theft, or embezzlement to finance gambling
- has jeopardized or lost a significant relationship, job, or educational or career opportunity because of gambling
- 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