Effects of dopamine agonist dose and gender on the prognosis of impulse control disorders in Parkinson's disease

https://doi.org/10.1016/j.parkreldis.2012.06.005Get rights and content

Abstract

Introduction

Cross-sectional studies have demonstrated that Parkinson's disease patients have an increased risk of impulse control disorders, and that the disorders frequently co-exist with depressive symptoms. There have been no previous large-scale prospective studies investigating predictive and prognostic factors of these disorders.

Methods

A population of 290 Parkinson's disease patients was studied at baseline and approximately 15 months later. The same screening methodology was used at both time-points (demographic and medication data together with the Questionnaire for Impulsive-compulsive Disorders in Parkinson's disease and the Beck Depression Inventory). The data was analyzed separating patients with and without impulse control disorders at baseline to obtain clinically useful prognostic factors.

Results

In patients who had impulse control disorders at baseline (n = 119), high dopamine agonist dose was associated with the presence of disorders at follow-up. Dopamine agonist levodopa equivalent daily dose over 160 mg was significantly associated with impulse control disorders with a positive predictive value of 92.5% (95% confidence interval 79.6%–98.4%). In addition, females had a better prognosis of impulse control disorders compared to males. The development of novel impulse control disorders (no disorder at baseline, disorder at follow-up) was associated with a concurrent increase in depression scores.

Conclusions

The results suggest that dopamine agonist dose and gender are associated with the prognosis of impulse control disorders. Symptoms of depression emerge together with novel impulse control disorders in Parkinson's disease.

Introduction

Cross-sectional studies have revealed clear associations between impulse control disorders (ICDs) and antiparkinsonian medications. In particular, these associations have been seen with dopamine agonists, also in the context of non-Parkinsonian disorders, such as the restless legs syndrome [1], [2]. There are additional anecdotal reports of resolved ICDs after discontinuation of dopamine agonists in Parkinson’ disease (PD) patients [3], [4], [5], [6], [7]. However, ICDs also occur in the absence of dopamine agonists, and they have been linked to other dopaminergic medication types apart from dopamine agonists [8], [9]. There is mixed evidence concerning the possible dose-dependent effects of these medications on ICDs [10]. In the largest cross-sectional epidemiological study so far [9], although an association of dopamine agonists and ICDs was seen, there was no clear evidence of a dose-dependent effect. Also in our previous cross-sectional study with 575 PD patients, no significant relationship between dopamine agonist dose and ICD prevalence was seen [11]. However, cross-sectional studies lack the power to detect possible delayed and dose-dependent effects due to considerable inter-individual variation in both the optimal agonist dose for treating motor symptoms of PD, and in the severity and characteristics of ICDs. The excess variation can be partially controlled for in within-subject longitudinal studies. To date, only a few prospective follow-up studies with small numbers of PD patients with ICDs have been published. For a clinical practitioner, the knowledge of possible dose-related effects of dopamine agonists on ICDs would be useful since the complete discontinuation of dopamine agonists due to an ICD can be difficult because of worsening motor symptoms and the possibility of dopamine agonist withdrawal syndrome [12].

In this study, we investigated the stability and prognostic factors of ICDs in PD patients at baseline and after a follow-up of approximately 15 months. Our aim was to explore dose-dependence of medications and other factors that could be useful for clinicians treating PD. There were two focuses in the study: 1) factors that could predict the resolving of an ICD (ICD at baseline, but no ICD at follow-up) and 2) factors that could predict the appearance of an ICD (no ICD at baseline, but ICD at follow-up). In addition, special attention was addressed to temporal relationships between depression and ICDs in PD.

Section snippets

Participants

The first survey was sent to 1000 patients and 575 responders were included in the published cross-sectional study as described previously [11]. The second survey was sent to all 376 subjects who had indicated in the first study that they were willing to participate. Two hundred ninety-six patients out of 376 (78.7%) participated, six subjects were excluded because of inadequate data, and thus the final data set consisted of 290 patients investigated at baseline and follow-up. However, only 270

Patients and surveys

Of the 290 patients, 62.4% (n = 181) were males. The median (IQR) follow-up time was 449 (440–456) days. In the follow-up examination, mean (95% CI) levodopa dose (and subsequently total LEDD) had significantly increased by 46.4 mg (15.5–77.4) and there were more patients using levodopa (n = 220 at baseline, n = 236 at follow-up, P < 0.001) reflecting treatment interventions for PD symptom progression. There were no differences in the doses or in the number of patients using dopamine agonists,

Discussion

This is the first large-scale prospective study with two time-points investigating ICDs in PD. The results suggest a dose-dependent effect of dopamine agonists on ICDs. The results also suggest that the male sex is associated with more persistent ICDs, and indicate that depression is associated with the development of ICDs.

The first focus of the present study was to detect factors associated with resolving ICDs. Two independent factors were found: low dopamine agonist dose at baseline and the

Conclusions

In summary, the results of this study suggest that dopamine agonist dose and gender are associated with the outcome of ICDs in patients with Parkinson's disease. Depressive symptoms increase in parallel with the development of new ICDs.

Funding

This work was supported by the Finnish Alcohol Research Foundation, the Finnish Medical Foundation, the Turku University Hospital (EVO-funds), the Turku University Foundation, the Paulo Foundation, and the Finnish Parkinson Foundation.

Conflict of interest

Juho Joutsa has received lecturer honoraria from Boehringer-Ingelheim. Kirsti Martikainen has received lecture and/or consultant fees from Boehringer-Ingelheim, GlaxoSmithKline, UCB Pharma, and Orion Pharma. Tero Vahlberg discloses no financial interests. Valtteri Kaasinen has received speaker honoraria and/or travel grants from Boehringer-Ingelheim, Orion-Pharma, Abbott, UCB Pharma and Lundbeck; and serves as a member of the advisory board of UCB Pharma and as a consultant for Orion-Pharma and

Acknowledgments

The authors thank Hannele Hyppönen from the Finnish Parkinson Foundation for her skillfull assistance during the study.

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