Estimated frequencies of compulsive gambling in PD range from 0.5%(1
) to 4.9%(2
). Our frequency estimate for compulsive gambling (2.2% for active cases and 2.6% for anytime during PD) fell in the intermediate range of those previously reported. We may have underestimated the frequency of ICDs in our population, as patients may have been either hesitant to acknowledge symptoms or less likely to be present in the clinic and therefore unavailable for screening.
There is no published literature on the estimated prevalence of other ICDs in PD. We found that compulsive sexual behavior was as common as compulsive gambling, though may have been due to the predominance of males in our sample. Regardless, our findings are consistent with recent reports(7
) suggesting an association between dopamine agonist treatment and compulsive sexual behavior in PD.
Of the six potential risk factors for ICDs identified in preliminary analyses, only dopamine agonist treatment and a history of ICD symptomatology prior to PD predicted presence of an active ICD in the multivariate model. Previous reporting of younger PD patients being disproportionately affected with ICDs may reflect prescribing patterns (e.g., older patients are less likely to be treated with a dopamine agonist). Our data suggest that a history of ICD symptomatology prior to PD is the main demographic or clinical variable that predicts an increased risk for the development of an ICD in the setting of dopamine agonist treatment.
The risk associated with ICDs was specific to the dopamine agonist medication class. Although there was a suggestion on univariate analysis of an association between the total LEDD and ICDs, this relationship was no longer observed after controlling for dopamine agonist use. These results suggest a distinct mechanism of action, as opposed to an additive effect, for dopamine agonists in the development of ICDs.
Our findings did not support a differential association between specific dopamine agonists and ICDs, suggesting a class effect. Two case series(2
) implicated pramipexole as the agent most likely to cause an ICD, but neither accounted for the relative frequency of pramipexole use in comparison with other dopamine agonists.
There is great variability in the dosing of dopamine agonists in PD. Using LEDDs to examine the three dopamine agonists as a class, ICD cases were treated with higher dopamine agonist doses. These findings are consistent with two case series(2
) suggesting that the greatest risk for ICDs may involve dopamine agonist doses at the high end of the therapeutic range. If true, that may help explain why the highest frequency of ICD cases, even though not statistically significant, was in pergolide-treated patients, as this group was more likely to receive doses at the upper end of the therapeutic range.
Limitations of our study include the following: (1
) Our study population was not randomly chosen; (2
) Subjects came from two centers (including one veterans’ hospital) in one region of the country, limiting the generalizability of our findings; (3
) The follow-up phone interview to verify the history of ICD behaviors was conducted up to 15 months after the screening process, which may have affected the validity of the data; (4
) No measures of PD severity, other than duration of illness, were available for analysis; (5
) ICD status was determined through the use of the MIDI rather than formal diagnostic interviews, and determination of ICD symptomatology prior to PD onset was based on the unstructured screening interview only; and (6
) Only 11 ICD cases were identified, limiting the conclusions that can be reached about the nature of the associations between dopamine agonist treatment and ICDs in PD. Multi-site studies involving larger, random samples of patients are needed to definitively determine the prevalence and clinical correlates of ICDs in PD.
Our findings highlight the importance of screening for a variety of ICDs in PD patients treated with a dopamine agonist, particularly since only one-quarter of active ICD cases in this study had been identified clinically. It is not known whether the risk for ICDs with exposure to this medication class is specific to PD patients. As dopamine agonists are increasingly prescribed for other indications (e.g., recent FDA approval of ropinirole for the treatment of restless legs syndrome), it will be important to assess the prevalence and risk for ICDs in other dopamine agonist-treated populations.