Longitudinal analysis of impulse control disorders in Parkinson disease

doi:10.1212/WNL.0000000000005816

Multicenter Study

. 2018 Jul 17;91(3):e189-e201.

doi: 10.1212/WNL.0000000000005816. Epub 2018 Jun 20.

Longitudinal analysis of impulse control disorders in Parkinson disease

Jean-Christophe Corvol¹, Fanny Artaud², Florence Cormier-Dequaire², Olivier Rascol², Franck Durif², Pascal Derkinderen², Ana-Raquel Marques², Frédéric Bourdain², Jean-Philippe Brandel², Fernando Pico², Lucette Lacomblez², Cecilia Bonnet², Christine Brefel-Courbon², Fabienne Ory-Magne², David Grabli², Stephan Klebe², Graziella Mangone², Hana You², Valérie Mesnage², Pei-Chen Lee², Alexis Brice², Marie Vidailhet², Alexis Elbaz²; DIGPD Study Group

Collaborators, Affiliations

Collaborators

DIGPD Study Group:
Jean-Christophe Corvol, Alexis Elbaz, Marie Vidailhet, Alexis Brice, Alexis Elbaz, Fanny Artaud, Frédéric Bourdain, Jean-Philippe Brandel, Jean-Christophe Corvol, Pascal Derkinderen, Franck Durif, Richard Levy, Fernando Pico, Olivier Rascol, Anne-Marie Bonnet, Cecilia Bonnet, Christine Brefel-Courbon, Florence Cormier-Dequaire, Bertrand Degos, Bérangère Debilly, Alexis Elbaz, Monique Galitsky, David Grabli, Andreas Hartmann, Stephan Klebe, Julia Kraemmer, Lucette Lacomblez, Sara Leder, Graziella Mangone, Louise-Laure Mariani, Ana-Raquel Marques, Valérie Mesnage, Julia Muellner, Fabienne Ory-Magne, Violaine Planté-Bordeneuve, Emmanuel Roze, Melissa Tir, Marie Vidailhet, Hana You, Eve Benchetrit, Julie Socha, Fanny Pineau, Tiphaine Vidal, Elsa Pomies, Virginie Bayet, Alexis Brice, Suzanne Lesage, Khadija Tahiri, Hélène Bertrand, Graziella Mangone, Alain Mallet, Coralie Villeret, Merry Mazmanian, Hakima Manseur, Mostafa Hajji, Benjamin Le Toullec, Vanessa Brochard, Monica Roy, Isabelle Rieu, Stéphane Bernard, Antoine Faurie-Grepon

Affiliations

¹ From the Assistance Publique Hôpitaux de Paris (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); Sorbonne Université (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); INSERM (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.), Institut du cerveau et de la Moelle, Centre d'Investigation Clinique Neurosciences, NS-PARK/FCRIN Network; CNRS (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); Departments of Neurology and Genetics (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.), Hôpital Pitié-Salpêtrière, Paris; CESP (F.A., A.E.), Faculte de médecine, Université Paris-Sud; Faculte de médecine (F.A., A.E.), UVSQ, Institut National de la Santé et de la Recherche Médicale, Université Paris-Saclay, Villejuif; University of Toulouse 3 (O.R., C.B.-C., F.O.-M), Centre Hospitalo-Universitaire de Toulouse and INSERM; Centre d'Investigation Clinique CIC1436 (O.R., C.B.-C., F.O.-M), NS-PARK/FCRIN Network, Départements de Neurosciences et de Pharmacologie Clinique, NeuroToul COEN Center, Toulouse; Department of Neurology (F.D., A.-R.M.), NS-PARK/FCRIN Network, Centre Hospitalo-Universitaire de Clermont-Ferrand; Department of Neurology (P.D.), NS-PARK/FCRIN Network, Centre Hospitalo-Universitaire de Nantes; Department of Neurology (F.B.), Hôpital Foch, Suresnes; Department of Neurology (J.-P.B.), Fondation Rothschild, Paris; Department of Neurology (F.P.), Centre Hospitalier de Versailles; Université Versailles Saint Quentin en Yvelines et Paris Saclay (F.P.), Versailles; Department of Neurology (V.M.), Centre Hospitalo-Universitaire Saint-Antoine, Paris, France; and Department of Health Care Management (P.-C.L.), College of Health Technology, National Taipei University of Nursing and Health Sciences, Taiwan. jean-christophe.corvol@aphp.fr.
² From the Assistance Publique Hôpitaux de Paris (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); Sorbonne Université (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); INSERM (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.), Institut du cerveau et de la Moelle, Centre d'Investigation Clinique Neurosciences, NS-PARK/FCRIN Network; CNRS (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); Departments of Neurology and Genetics (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.), Hôpital Pitié-Salpêtrière, Paris; CESP (F.A., A.E.), Faculte de médecine, Université Paris-Sud; Faculte de médecine (F.A., A.E.), UVSQ, Institut National de la Santé et de la Recherche Médicale, Université Paris-Saclay, Villejuif; University of Toulouse 3 (O.R., C.B.-C., F.O.-M), Centre Hospitalo-Universitaire de Toulouse and INSERM; Centre d'Investigation Clinique CIC1436 (O.R., C.B.-C., F.O.-M), NS-PARK/FCRIN Network, Départements de Neurosciences et de Pharmacologie Clinique, NeuroToul COEN Center, Toulouse; Department of Neurology (F.D., A.-R.M.), NS-PARK/FCRIN Network, Centre Hospitalo-Universitaire de Clermont-Ferrand; Department of Neurology (P.D.), NS-PARK/FCRIN Network, Centre Hospitalo-Universitaire de Nantes; Department of Neurology (F.B.), Hôpital Foch, Suresnes; Department of Neurology (J.-P.B.), Fondation Rothschild, Paris; Department of Neurology (F.P.), Centre Hospitalier de Versailles; Université Versailles Saint Quentin en Yvelines et Paris Saclay (F.P.), Versailles; Department of Neurology (V.M.), Centre Hospitalo-Universitaire Saint-Antoine, Paris, France; and Department of Health Care Management (P.-C.L.), College of Health Technology, National Taipei University of Nursing and Health Sciences, Taiwan.

PMID: 29925549
PMCID: PMC6059034
DOI: 10.1212/WNL.0000000000005816

Multicenter Study

Longitudinal analysis of impulse control disorders in Parkinson disease

Jean-Christophe Corvol et al. Neurology. 2018.

. 2018 Jul 17;91(3):e189-e201.

doi: 10.1212/WNL.0000000000005816. Epub 2018 Jun 20.

Authors

Collaborators

DIGPD Study Group:
Jean-Christophe Corvol, Alexis Elbaz, Marie Vidailhet, Alexis Brice, Alexis Elbaz, Fanny Artaud, Frédéric Bourdain, Jean-Philippe Brandel, Jean-Christophe Corvol, Pascal Derkinderen, Franck Durif, Richard Levy, Fernando Pico, Olivier Rascol, Anne-Marie Bonnet, Cecilia Bonnet, Christine Brefel-Courbon, Florence Cormier-Dequaire, Bertrand Degos, Bérangère Debilly, Alexis Elbaz, Monique Galitsky, David Grabli, Andreas Hartmann, Stephan Klebe, Julia Kraemmer, Lucette Lacomblez, Sara Leder, Graziella Mangone, Louise-Laure Mariani, Ana-Raquel Marques, Valérie Mesnage, Julia Muellner, Fabienne Ory-Magne, Violaine Planté-Bordeneuve, Emmanuel Roze, Melissa Tir, Marie Vidailhet, Hana You, Eve Benchetrit, Julie Socha, Fanny Pineau, Tiphaine Vidal, Elsa Pomies, Virginie Bayet, Alexis Brice, Suzanne Lesage, Khadija Tahiri, Hélène Bertrand, Graziella Mangone, Alain Mallet, Coralie Villeret, Merry Mazmanian, Hakima Manseur, Mostafa Hajji, Benjamin Le Toullec, Vanessa Brochard, Monica Roy, Isabelle Rieu, Stéphane Bernard, Antoine Faurie-Grepon

Affiliations

¹ From the Assistance Publique Hôpitaux de Paris (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); Sorbonne Université (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); INSERM (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.), Institut du cerveau et de la Moelle, Centre d'Investigation Clinique Neurosciences, NS-PARK/FCRIN Network; CNRS (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); Departments of Neurology and Genetics (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.), Hôpital Pitié-Salpêtrière, Paris; CESP (F.A., A.E.), Faculte de médecine, Université Paris-Sud; Faculte de médecine (F.A., A.E.), UVSQ, Institut National de la Santé et de la Recherche Médicale, Université Paris-Saclay, Villejuif; University of Toulouse 3 (O.R., C.B.-C., F.O.-M), Centre Hospitalo-Universitaire de Toulouse and INSERM; Centre d'Investigation Clinique CIC1436 (O.R., C.B.-C., F.O.-M), NS-PARK/FCRIN Network, Départements de Neurosciences et de Pharmacologie Clinique, NeuroToul COEN Center, Toulouse; Department of Neurology (F.D., A.-R.M.), NS-PARK/FCRIN Network, Centre Hospitalo-Universitaire de Clermont-Ferrand; Department of Neurology (P.D.), NS-PARK/FCRIN Network, Centre Hospitalo-Universitaire de Nantes; Department of Neurology (F.B.), Hôpital Foch, Suresnes; Department of Neurology (J.-P.B.), Fondation Rothschild, Paris; Department of Neurology (F.P.), Centre Hospitalier de Versailles; Université Versailles Saint Quentin en Yvelines et Paris Saclay (F.P.), Versailles; Department of Neurology (V.M.), Centre Hospitalo-Universitaire Saint-Antoine, Paris, France; and Department of Health Care Management (P.-C.L.), College of Health Technology, National Taipei University of Nursing and Health Sciences, Taiwan. jean-christophe.corvol@aphp.fr.
² From the Assistance Publique Hôpitaux de Paris (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); Sorbonne Université (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); INSERM (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.), Institut du cerveau et de la Moelle, Centre d'Investigation Clinique Neurosciences, NS-PARK/FCRIN Network; CNRS (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); Departments of Neurology and Genetics (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.), Hôpital Pitié-Salpêtrière, Paris; CESP (F.A., A.E.), Faculte de médecine, Université Paris-Sud; Faculte de médecine (F.A., A.E.), UVSQ, Institut National de la Santé et de la Recherche Médicale, Université Paris-Saclay, Villejuif; University of Toulouse 3 (O.R., C.B.-C., F.O.-M), Centre Hospitalo-Universitaire de Toulouse and INSERM; Centre d'Investigation Clinique CIC1436 (O.R., C.B.-C., F.O.-M), NS-PARK/FCRIN Network, Départements de Neurosciences et de Pharmacologie Clinique, NeuroToul COEN Center, Toulouse; Department of Neurology (F.D., A.-R.M.), NS-PARK/FCRIN Network, Centre Hospitalo-Universitaire de Clermont-Ferrand; Department of Neurology (P.D.), NS-PARK/FCRIN Network, Centre Hospitalo-Universitaire de Nantes; Department of Neurology (F.B.), Hôpital Foch, Suresnes; Department of Neurology (J.-P.B.), Fondation Rothschild, Paris; Department of Neurology (F.P.), Centre Hospitalier de Versailles; Université Versailles Saint Quentin en Yvelines et Paris Saclay (F.P.), Versailles; Department of Neurology (V.M.), Centre Hospitalo-Universitaire Saint-Antoine, Paris, France; and Department of Health Care Management (P.-C.L.), College of Health Technology, National Taipei University of Nursing and Health Sciences, Taiwan.

PMID: 29925549
PMCID: PMC6059034
DOI: 10.1212/WNL.0000000000005816

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.

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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.

See this image and copyright information in PMC

Comment in

Don't ask, don't tell: Impulse control disorders in PD.
Boylan LS, Kostić VS. Boylan LS, et al. Neurology. 2018 Jul 17;91(3):107-108. doi: 10.1212/WNL.0000000000005806. Epub 2018 Jun 20. Neurology. 2018. PMID: 29925552 No abstract available.

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References

1. Evans AH, Strafella AP, Weintraub D, Stacy M. Impulsive and compulsive behaviors in Parkinson's disease. Mov Disord 2009;24:1561–1570. - PubMed
1. Callesen MB, Weintraub D, Damholdt MF, Moller A. Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: prevalence, depression, and personality. Parkinsonism Relat Disord 2014;20:22–26. - PubMed
1. Smith KM, Xie SX, Weintraub D. Incident impulse control disorder symptoms and dopamine transporter imaging in Parkinson disease. J Neurol Neurosurg Psychiatry 2016;87:864–870. - PMC - PubMed
1. Weintraub D, Koester J, Potenza MN, et al. . Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol 2010;67:589–595. - PubMed
1. Voon V, Fox SH. Medication-related impulse control and repetitive behaviors in Parkinson disease. Arch Neurol 2007;64:1089–1096. - PubMed

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[1] Evans AH, Strafella AP, Weintraub D, Stacy M. Impulsive and compulsive behaviors in Parkinson's disease. Mov Disord 2009;24:1561–1570. - PubMed

[2] Evans AH, Strafella AP, Weintraub D, Stacy M. Impulsive and compulsive behaviors in Parkinson's disease. Mov Disord 2009;24:1561–1570. - PubMed

[3] Callesen MB, Weintraub D, Damholdt MF, Moller A. Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: prevalence, depression, and personality. Parkinsonism Relat Disord 2014;20:22–26. - PubMed

[4] Callesen MB, Weintraub D, Damholdt MF, Moller A. Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: prevalence, depression, and personality. Parkinsonism Relat Disord 2014;20:22–26. - PubMed

[5] Smith KM, Xie SX, Weintraub D. Incident impulse control disorder symptoms and dopamine transporter imaging in Parkinson disease. J Neurol Neurosurg Psychiatry 2016;87:864–870. - PMC - PubMed

[6] Smith KM, Xie SX, Weintraub D. Incident impulse control disorder symptoms and dopamine transporter imaging in Parkinson disease. J Neurol Neurosurg Psychiatry 2016;87:864–870. - PMC - PubMed

[7] Weintraub D, Koester J, Potenza MN, et al. . Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol 2010;67:589–595. - PubMed

[8] Weintraub D, Koester J, Potenza MN, et al. . Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol 2010;67:589–595. - PubMed

[9] Voon V, Fox SH. Medication-related impulse control and repetitive behaviors in Parkinson disease. Arch Neurol 2007;64:1089–1096. - PubMed

[10] Voon V, Fox SH. Medication-related impulse control and repetitive behaviors in Parkinson disease. Arch Neurol 2007;64:1089–1096. - PubMed

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Longitudinal analysis of impulse control disorders in Parkinson disease

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Longitudinal analysis of impulse control disorders in Parkinson disease

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