To our knowledge this is the first case series examining in the context of routine care the long-term clinical outcomes of PD patients with ICDs. We found that on average patients had a significant change in their specific dopamine replacement therapies once their ICD was identified, and that all patients who discontinued or significantly decreased DA treatment experienced full remission or a clinically significant reduction in ICD symptomatology. This was consistent with our hypothesis that decreases in exposure to DA therapy would be associated with improvement in ICD symptoms.
There are several limitations to this study. First, we were unable to contact all eligible subjects, although over 80% of the original ICD sample did participate in the follow-up interview. Second, the sample size was relatively small, only identified ICD patients on a DA, and involved patients at two movement disorders centers with a research focus on the psychiatric complications of PD, limiting the generalizability of the findings. Third, the data were obtained primarily via telephone interview. In-person interviews may have yielded more accurate and complete information. Finally, this study was not controlled, limiting conclusions that could be drawn. For example, it is possible that the overall decrease in DA exposure was unrelated to improvement in ICD symptoms, as the natural histories of ICDs in PD and non-PD individuals are not well understood.
The results of this study results provide further evidence of the association between DA treatment and ICD behaviors in PD. Because of the long lag-time reported in many cases between DA initiation and development of ICD behaviors, it is not practical to conduct a randomized trial to definitively determine the association between DA treatment and ICDs. Additionally, given the existing evidence in support of the association between ICDs and DA treatment, it does not seem ethical to conduct a randomized DA discontinuation study in PD patients with an ICD. Thus, the best available evidence regarding the impact of DA treatment on ICD behaviors is likely to come from cross-sectional studies and careful long-term follow-up of clinical populations.
Our results are consistent with previous case reporting that discontinuation or reduction in DA treatment leads to a reduction or resolution of ICD symptoms. They are also similar to the outcomes of the small group of ICD patients who underwent STN DBS surgery, all of whom experienced resolution of ICD symptomatology post-DBS surgery and in the context of treatment with significantly lower total LEDD.15
We found that patients overall were being treated with similar total LEDDs at the two time periods, but that there was an overall shift in the balance between l
-dopa and DA treatment. At Time 1, patients were on essentially the same daily l
-dopa and DA LEDD dosage, but at Time 2 the balance shifted in favor of l
-dopa treatment, with the daily l
-dopa dosage being nearly four times as high as the DA LEDD dosage. The lack of change in UPDRS motor score over time suggests that overall it is possible to adequately manage motor symptoms in ICD patients by shifting the balance away from DA treatment to l
-dopa treatment. Though there may be long-term adverse effects (e.g., dyskinesias or motor fluctuations) from chronic, higher-dose l
our results in conjunction with those of patients undergoing surgery suggest that two possible management strategies for ICD symptoms in PD are shifting the l
-dopa:DA balance in favor of l
-dopa and STN DBS surgery, the latter leading to a decrease in overall dopaminergic treatment. However, it is important to note a recent case report of a patient on long-term DA treatment who developed pathological gambling only after post-bilateral STN DBS and in the context of cognitive decline.21
The urge to gamble resolved after switching off the neurostimulation. Upon restimulation with different parameters, ICD symptoms reoccurred, and only with discontinuation of DA treatment was the patient able to continue with STN stimulation. Thus, the relationship between ICD symptomatology and PD treatments, particularly within the context of individual patient characteristics, requires additional investigation.
It is also important to determine if other treatment strategies may be effective for ICDs in PD that arise in the context of DA use. One of the patients in this study experienced partial remission of ICD symptomatology in spite of continuing the same DA at the same dosage, suggesting that other factors may contribute to changes in ICD symptoms over time. In addition, many PD patients are reluctant to discontinue DA treatment because of the motor benefits associated with their use. Thus, randomized treatment studies using psychiatric medications that have been reported to be helpful in the treatment of ICDs in PD, such as atypical antipsychotics and antidepressants, are needed. Finally, the role for psychosocial interventions, such as participation in Gamblers’ Anonymous, has yet to be studied. However, while waiting for other treatment strategies to be tested, one relatively simple and apparently effective way to manage ICDs that occur during DA treatment is to decrease DA exposure and consider a concomitant increase in l-dopa treatment.