Longitudinal analysis of impulse control disorders in Parkinson disease

Abstract

Objective: To investigate the longitudinal dose-effect relationship between dopamine replacement therapy and impulse control disorders (ICDs) in Parkinson disease (PD).

Methods: We used data from a multicenter longitudinal cohort of consecutive patients with PD with ≤5 years' disease duration at baseline followed up annually up to 5 years. ICDs were evaluated during face-to-face semistructured interviews with movement disorder specialists. Generalized estimating equations and Poisson models with robust variance were used to study the association between several time-dependent definitions of dopamine agonist (DA) use, taking dose and duration of treatment into account, and ICDs at each visit. Other antiparkinsonian drugs were also examined.

Results: Among 411 patients (40.6% women, mean age 62.3 years, average follow-up 3.3 years, SD 1.7 years), 356 (86.6%) took a DA at least once since disease onset. In 306 patients without ICDs at baseline, the 5-year cumulative incidence of ICDs was 46.1% (95% confidence interval [CI] 37.4-55.7, DA ever users 51.5% [95% CI 41.8-62.1], DA never users 12.4% [95% CI 4.8-30.0]). ICD prevalence increased from 19.7% at baseline to 32.8% after 5 years. ICDs were associated with ever DA use (prevalence ratio 4.23, 95% CI 1.78-10.09). Lifetime average daily dose and duration of treatment were independently associated with ICDs with significant dose-effect relationships. Similar analyses for levodopa were not in favor of a strong association. ICDs progressively resolved after DA discontinuation.

Conclusion: In this longitudinal study of patients with PD characterized by a high prevalence of DA treatment, the 5-year cumulative incidence of ICDs was ≈46%. ICDs were strongly associated with DA use with a dose-effect relationship; both increasing duration and dose were associated with ICDs. ICDs progressively resolved after DA discontinuation.

Clinicaltrialsgov identifier: NCT01564992.

© 2018 American Academy of Neurology.

Figures

Figure 1. Cumulative incidence (95% confidence interval) of ICDs at each visit according to ever use of dopamine agonists

ICD = impulse control disorder.

Figure 2. Dose-effect relationship between different measures of DA use and prevalence of ICDs (A) overall and (B) in DA users

Graphs show the prevalence of impulse control disorder (ICDs) after 3 years of follow-up in women with average age (62 years) and disease duration (2.6 years) at baseline who were married, had a low level education level, and never used levodopa. DA = dopamine agonist; LED = levodopa equivalent dose.

Figure 3. Probability of staying with ICDs over the follow-up in patients who discontinued DAs

Note that t = 0 corresponds to the date of discontinuation of dopamine agonists (DAs). ICD = impulse control disorder.