Skip to main content
SpringerLink
Log in

Improvement of impulse control disorders associated with levodopa–carbidopa intestinal gel treatment in advanced Parkinson’s disease

Journal of Neurology Aims and scope Submit manuscript

Cite this article

Abstract

Impulse control behaviors are a frequent comorbidity for patients with Parkinson’s disease (PD). The objective of the present study was to evaluate the effectiveness levodopa–carbidopa intestinal gel (LCIG) therapy on impulse control disorders (ICDs) in patients with advanced PD. We conducted a multicenter, observational, and prospective (6 months follow-up) study that included consecutive PD patients assigned to LCIG through routine medical practice. Patients completed visits at baseline, 1, 3, and 6 months after percutaneous endoscopic gastrostomy procedure. The following outcomes were evaluated: presence and severity of ICDs and other neuropsychiatric disorders, sleep disturbances, patients’ quality of life, and caregivers’ burden. Sixty-two patients were included at baseline: mean age 72.2 years (SD ± 7.0), 42% women. Median duration of PD symptoms was 13.5 years (IQR 5.5–21.5) and median time with motor fluctuations was 5.0 years (IQR 1.0–9.0). Treatment with LCIG infusion was associated with progressive and significant improvements in ICDs symptoms over the study period (64.4% reduction in the Questionnaire for Impulsive–Compulsive Disorders in Parkinson’s disease—Rating Scale score). Psychotic and other neuropsychiatric symptoms were also significantly reduced, and patients’ sleep quality and psychosocial function improved. Caregivers’ burden remained unchanged. There was a significant improvement in the daily “Off” time [7.4 h (SD ± 4.0) vs 1.5 h (SD ± 1.8); p < 0.0001] at the end of follow-up, whereas duration of dyskinesias was not affected. ICDs significantly improved after 6-month LCIG treatment in a group of PD patients with mild-to-moderate neuropsychiatric disturbances.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55:259–272

    Article  PubMed  CAS  Google Scholar 

  2. Takahashi H, Wakabayashi K (2001) The cellular pathology of Parkinson’s disease. Neuropathology 21:315–322

    Article  PubMed  CAS  Google Scholar 

  3. Obeso JA, Olanow CW, Nutt JG (2000) Levodopa motor complications in Parkinson’s disease. Trends Neurosci 23:S2–S7

    Article  PubMed  CAS  Google Scholar 

  4. Barone P, Amboni M, Vitale C, Bonavita V (2004) Treatment of nocturnal disturbances and excessive daytime sleepiness in Parkinson’s disease. Neurology 63:S35–S38

    Article  PubMed  Google Scholar 

  5. Weintraub D, Koester J, Potenza MN et al (2010) Impulse control disorders in parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol 67:589–595. https://doi.org/10.1001/archneurol.2010.65

    Article  PubMed  Google Scholar 

  6. Weintraub D, Hoops S, Shea JA, Lyons KE, Pahwa R, Driver-Dunckley ED, Adler CH, Potenza MN, Miyasaki J, Siderowf AD, Duda JE, Hurtig HI, Colcher A, Horn SS, Stern MB, Voon V (2009) Validation of the questionnaire for impulsive-compulsive disorders in Parkinson’s disease. Mov Disord 24:1461–1467. https://doi.org/10.1002/mds.22571

    Article  PubMed  PubMed Central  Google Scholar 

  7. Nyholm D (2006) Enteral levodopa/carbidopa gel infusion for the treatment of motor fluctuations and dyskinesias in advanced Parkinson’s disease. Expert Rev Neurother 6:1403–1411. https://doi.org/10.1586/14737175.6.10.1403

    Article  PubMed  CAS  Google Scholar 

  8. Honig H, Antonini A, Martinez-Martin P, Forgacs I, Faye GC, Fox T, Fox K, Mancini F, Canesi M, Odin P, Chaudhuri KR (2009) Intrajejunal levodopa infusion in Parkinson’s disease: a pilot multicenter study of effects on nonmotor symptoms and quality of life. Mov Disord 24:1468–1474. https://doi.org/10.1002/mds.22596

    Article  PubMed  Google Scholar 

  9. Puente V, De Fabregues O, Oliveras C, Ribera G, Pont-Sunyer C, Vivanco R, Cucurella G, Giralt E, Delgado T, Garcia C, Seoane A, Campo R (2010) Eighteen month study of continuous intraduodenal levodopa infusion in patients with advanced Parkinson’s disease: impact on control of fluctuations and quality of life. Parkinsonism Relat Disord 16:218–221. https://doi.org/10.1016/j.parkreldis.2009.07.015

    Article  PubMed  CAS  Google Scholar 

  10. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Lobo A, Saz P, Marcos G, Dia JL, de la Camara C, Ventura T, Morales Asin F, Fernando Pascual L, Montanes JA, Aznar S (1999) Revalidation and standardization of the cognition mini-exam (first Spanish version of the Mini-Mental Status Examination) in the general geriatric population. Med Clin 112:767–774

    CAS  Google Scholar 

  12. Fahn S, Elton R (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden C, Calne D, Goldstein M (eds) Recent development in Parkinson’s disease Macmillan Healthcare. Florham Park, NJ, pp 153–163

    Google Scholar 

  13. Martinez-Martin P, Rodriguez-Blazquez C, Forjaz MJ, de Pedro J (2009) The clinical impression of severity Index for Parkinson’s Disease: international validation study. Mov Disord 24:211–217. https://doi.org/10.1002/mds.22320

    Article  PubMed  Google Scholar 

  14. Martinez-Martin P, Frades-Payo B, Aguera-Ortiz L, Ayuga-Martinez A (2012) A short scale for evaluation of neuropsychiatric disorders in Parkinson’s disease: first psychometric approach. J Neurol 259:2299–2308. https://doi.org/10.1007/s00415-012-6490-x

    Article  PubMed  Google Scholar 

  15. Kaufer DI, Cummings JL, Ketchel P, Smith V, MacMillan A, Shelley T, Lopez OL, DeKosky ST (2000) Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. J Neuropsychiatr Clin Neurosci 12:233–239

    Article  CAS  Google Scholar 

  16. Dubois B, Burn D, Goetz C, Aarsland D, Brown RG, Broe GA, Dickson D, Duyckaerts C, Cummings J, Gauthier S, Korczyn A, Lees A, Levy R, Litvan I, Mizuno Y, McKeith IG, Olanow CW, Poewe W, Sampaio C, Tolosa E, Emre M (2007) Diagnostic procedures for Parkinson’s disease dementia: recommendations from the movement disorder society task force. Mov Disord 22:2314–2324. https://doi.org/10.1002/mds.21844

    Article  PubMed  Google Scholar 

  17. Martinez-Martin P, Visser M, Rodriguez-Blazquez C, Marinus J, Chaudhuri KR, van Hilten JJ (2008) SCOPA-sleep and PDSS: two scales for assessment of sleep disorder in Parkinson’s disease. Mov Disord 23:1681–1688. https://doi.org/10.1002/mds.22110

    Article  PubMed  Google Scholar 

  18. Marinus J, Visser M, Martı́nez-Martı́n P, van Hilten JJ, Stiggelbout AM (2003) A short psychosocial questionnaire for patients with Parkinson’s disease: the SCOPA-PS. J Clin Epidemiol 56:61–67. https://doi.org/10.1016/S0895-4356(02)00569-3

    Article  PubMed  Google Scholar 

  19. Martinez-Martin P, Forjaz MJ, Frades-Payo B, Rusinol AB, Fernandez-Garcia JM, Benito-Leon J, Arillo VC, Barbera MA, Sordo MP, Catalan MJ (2007) Caregiver burden in Parkinson’s disease. Mov Disord 22:924–931. https://doi.org/10.1002/mds.21355

    Article  PubMed  Google Scholar 

  20. Kazis LE, Anderson JJ, Meenan RF (1989) Effect sizes for interpreting changes in health status. Med Care 27:S178–S189

    Article  PubMed  CAS  Google Scholar 

  21. Norman GR, Sloan JA, Wyrwich KW (2003) Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care 41:582–592. https://doi.org/10.1097/01.mlr.0000062554.74615.4c

    Article  PubMed  Google Scholar 

  22. Voon V, Sohr M, Lang AE, Potenza MN, Siderowf AD, Whetteckey J, Weintraub D, Wunderlich GR, Stacy M (2011) Impulse control disorders in Parkinson disease: a multicenter case-control study. Ann Neurol 69:986–996. https://doi.org/10.1002/ana.22356

    Article  PubMed  Google Scholar 

  23. Phu AL, Xu Z, Brakoulias V, Mahant N, Fung VS, Moore GD, Martin A, Starcevic V, Krause M (2014) Effect of impulse control disorders on disability and quality of life in Parkinson’s disease patients. J Clin Neurosci 21:63–66. https://doi.org/10.1016/j.jocn.2013.02.032

    Article  PubMed  Google Scholar 

  24. Leroi I, Harbishettar V, Andrews M, McDonald K, Byrne EJ, Burns A (2012) Carer burden in apathy and impulse control disorders in Parkinson’s disease. Int J Geriatr Psychiatry 27:160–166. https://doi.org/10.1002/gps.2704

    Article  PubMed  Google Scholar 

  25. Callesen MB, Scheel-Kruger J, Kringelbach ML, Moller A (2013) A systematic review of impulse control disorders in Parkinson’s disease. J Parkinsons Dis 3:105–138. https://doi.org/10.3233/jpd-120165

    Article  PubMed  CAS  Google Scholar 

  26. Krishnamoorthy S, Rajan R, Banerjee M, Kumar H, Sarma G, Krishnan S, Sarma S, Kishore A (2016) Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson’s disease patients. Parkinsonism Relat Disord 30:13–17. https://doi.org/10.1016/j.parkreldis.2016.06.005

    Article  PubMed  Google Scholar 

  27. Garcia-Ruiz PJ, Martinez Castrillo JC, Alonso-Canovas A, Herranz Barcenas A, Vela L, Sanchez Alonso P, Mata M, Olmedilla Gonzalez N, Mahillo Fernandez I (2014) Impulse control disorder in patients with Parkinson’s disease under dopamine agonist therapy: a multicentre study. J Neurol Neurosurg Psychiatry 85:840–844. https://doi.org/10.1136/jnnp-2013-306787

    Article  PubMed  Google Scholar 

  28. Baumann-Vogel H, Valko PO, Eisele G, Baumann CR (2015) Impulse control disorders in Parkinson’s disease: don’t set your mind at rest by self-assessments. Eur J Neurol 22:603–609. https://doi.org/10.1111/ene.12646

    Article  PubMed  CAS  Google Scholar 

  29. Ricciardi L, Demartini B, Pomponi M, Ricciardi D, Morabito B, Renna R, Bernabei R, Bentivoglio AR (2016) Impulsive compulsive behaviours in Parkinson’s disease: patients’ versus caregivers’ perceptions. J Neurol 263:1019–1021. https://doi.org/10.1007/s00415-016-8079-2

    Article  PubMed  CAS  Google Scholar 

  30. Volkmann J, Albanese A, Antonini A, Chaudhuri KR, Clarke CE, de Bie RMA, Deuschl G, Eggert K, Houeto J-L, Kulisevsky J, Nyholm D, Odin P, Østergaard K, Poewe W, Pollak P, Rabey JM, Rascol O, Ruzicka E, Samuel M, Speelman H, Sydow O, Valldeoriola F, van der Linden C, Oertel W (2013) Selecting deep brain stimulation or infusion therapies in advanced Parkinson’s disease: an evidence-based review. J Neurol 260:2701–2714. https://doi.org/10.1007/s00415-012-6798-6

    Article  PubMed  PubMed Central  Google Scholar 

  31. Nyholm D, Lennernas H, Gomes-Trolin C, Aquilonius SM (2002) Levodopa pharmacokinetics and motor performance during activities of daily living in patients with Parkinson’s disease on individual drug combinations. Clin Neuropharmacol 25:89–96

    Article  PubMed  CAS  Google Scholar 

  32. Evans AH, Pavese N, Lawrence AD, Tai YF, Appel S, Doder M, Brooks DJ, Lees AJ, Piccini P (2006) Compulsive drug use linked to sensitized ventral striatal dopamine transmission. Ann Neurol 59:852–858. https://doi.org/10.1002/ana.20822

    Article  PubMed  CAS  Google Scholar 

  33. Todorova A, Samuel M, Brown RG, Chaudhuri KR (2015) Infusion therapies and development of impulse control disorders in advanced parkinson disease: clinical experience after 3 years’ Follow-up. Clin Neuropharmacol 38:132–134. https://doi.org/10.1097/wnf.0000000000000091

    Article  PubMed  Google Scholar 

  34. Catalan MJ, de Pablo-Fernandez E, Villanueva C, Fernandez-Diez S, Lapena-Montero T, Garcia-Ramos R, Lopez-Valdes E (2013) Levodopa infusion improves impulsivity and dopamine dysregulation syndrome in Parkinson’s disease. Mov Disord 28:2007–2010. https://doi.org/10.1002/mds.25636

    Article  PubMed  CAS  Google Scholar 

  35. Chang FC, Kwan V, van der Poorten D, Mahant N, Wolfe N, Ha AD, Griffith JM, Tsui D, Kim SD, Fung VS (2016) Intraduodenal levodopa-carbidopa intestinal gel infusion improves both motor performance and quality of life in advanced Parkinson’s disease. J Clin Neurosci 25:41–45. https://doi.org/10.1016/j.jocn.2015.05.059

    Article  PubMed  CAS  Google Scholar 

  36. Schrag A, Schott JM (2006) Epidemiological, clinical, and genetic characteristics of early onset parkinsonism. Lancet Neurol 5:355–363. https://doi.org/10.1016/s1474-4422(06)70411-2

    Article  PubMed  CAS  Google Scholar 

  37. Havlikova E, van Dijk JP, Nagyova I, Rosenberger J, Middel B, Dubayova T, Gdovinova Z, Groothoff JW (2011) The impact of sleep and mood disorders on quality of life in Parkinson’s disease patients. J Neurol 258:2222–2229. https://doi.org/10.1007/s00415-011-6098-6

    Article  PubMed  Google Scholar 

  38. Perez-Lloret S, Rossi M, Nouzeilles MI, Trenkwalder C, Cardinali DP, Merello M (2009) Parkinson’s disease sleep scale, sleep logs, and actigraphy in the evaluation of sleep in parkinsonian patients. J Neurol 256:1480–1484. https://doi.org/10.1007/s00415-009-5141-3

    Article  PubMed  PubMed Central  Google Scholar 

  39. Martinez-Martin P, Rodriguez-Blazquez C, Forjaz MJ, Frades-Payo B, Agüera-Ortiz L, Weintraub D, Riesco A, Kurtis MM, Chaudhuri KR (2015) Neuropsychiatric symptoms and caregiver’s burden in Parkinson’s disease. Parkinsonism Relat Disord 21:629–634. https://doi.org/10.1016/j.parkreldis.2015.03.024

    Article  PubMed  Google Scholar 

  40. Okai D, Askey-Jones S, Samuel M, O’Sullivan SS, Chaudhuri KR, Martin A, Mack J, Brown RG, David AS (2013) Trial of CBT for impulse control behaviors affecting Parkinson patients and their caregivers. Neurology 80:792–799. https://doi.org/10.1212/WNL.0b013e3182840678

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by Abbvie and the Foundation Neurociencias y Envejecimiento. Abbvie provided financial support for study implementation, data collection, and data analysis, but was not involved in the conduct or management of the study, or analysis or interpretation of data, or preparation of the paper.

The authors acknowledge all the patients and caregivers participating in this study. Thanks go to the team of nurses from all centers for their helpful collaboration, especially to Natividad Mariscal, Maravillas Bernal, Beatriz Gonzalez-Garcia, and Laura Vargas-Gonzalez. The authors also thank Karma Research S. L. for study monitoring, Análisis Estadísticos PeRTICA, S. L. for statistical analysis contribution, and Anabel Herrero for writing assistance (these services were funded by Abbvie).

Co-investigators (EDIS Study Group): Alejandro Barroso-Merinero (Hospital Universitario La Princesa, Madrid), Juan P Cabello de la Rosa (Hospital General Universitario de Ciudad Real), M Teresa Cáceres-Redondo (Hospital Universitario Virgen del Rocío, Sevilla), Fatima Carrillo (Hospital Universitario Virgen del Rocío, Sevilla), Elvira García-Cobos (Hospital Puerta de Hierro, Madrid), Itciar Gaston-Zubimendi (Complejo Hospitalario de Navarra, Pamplona, Navarra), María J Gómez-Heredia (Hospital Universitario Virgen de la Victoria, Málaga), Jaime Herreros-Rodríguez (Hospital Universitario 12 de Octubre, Madrid), Silvia Jesús (Hospital Universitario Virgen del Rocío, Sevilla), Lidia López (Hospital Universitario La Princesa, Madrid), Nuria Lopez-Ariztegui (Hospital Virgen de la Salud, Toledo), Juan J López-Lozano (Hospital Puerta de Hierro, Madrid), Rocío Malo de Molina (Hospital Insular de Las Palmas, Gran Canaria), Javier Marco-Llorente (Hospital Clínico Universitario de Valladolid), Idaira Martin-Santana (Hospital Insular de Las Palmas, Gran Canaria), Marina Mata (Hospital Puerta de Hierro, Madrid), Paloma Montero (Hospital Clínico San Carlos, Madrid), Francisco Perez-Errasquin (Hospital Universitario Virgen de la Victoria, Málaga), Ana Rojo (Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid), Julia Vaamonde (Hospital General Universitario de Ciudad Real).

Author information

Authors and Affiliations

  1. Movement Disorders Unit, Department of Neurology, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, 28040, Madrid, Spain

    Maria Jose Catalan

  2. Department of Neurology, University Hospital 12 de Octubre, Madrid, Spain

    Jose Antonio Molina-Arjona

  3. Movement Disorders Unit, Neurology and Clinical Neurophysiology Service, Seville Biomedicine Institute (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain

    Pablo Mir

  4. Department of Neurology, Hospital General Yagüe, Burgos, Spain

    Esther Cubo

  5. Department of Neurology, University Hospital Insular de Gran Canaria, Las Palmas, Gran Canaria, Spain

    Jose Matias Arbelo

  6. National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain

    Pablo Martinez-Martin

Authors
  1. Maria Jose Catalan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jose Antonio Molina-Arjona
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pablo Mir
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Esther Cubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jose Matias Arbelo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pablo Martinez-Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

On behalf of the EDIS Study Group

Contributions

MJC designed the study, interpreted data, and drafted, edited, and submitted the final article. AMA, PM, EC, and JMA contributed to recruitment of patients and the overall implementation of the study, revised the manuscript, and approved the final version to be published. PMM contributed to the design of the study and statistical analyses, revised the manuscript, and approved the final version to be published.

Corresponding author

Correspondence to Maria Jose Catalan.

Ethics declarations

Ethical standards

The study complies with the Declaration of Helsinki. Local ethics committees approved the EDIS study.

Conflicts of interest

Maria Jose Catalan has received honoraria for consulting, advisory services, speaking services and research from AbbVie Laboratories and Merz. Antonio Molina-Arjona declares he has no conflict of interest. Pablo Mir has received honoraria for lecturing or advisory boards from AbbVie, UCB, Allergan, and Merz, and research grants from the Ministerio de Economía y Competitividad de España [SAF2007-60700], Instituto de Salud Carlos III [PI10/01674, CP08/00174, PI13/01461], Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0377/2007, PI-0741/2010, PI-0437-2012], Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, and the Fundación Alicia Koplowitz. Esther Cubo has received travel grant to meetings from Abbvie and Allergan; speaker honorarium from Abbvie and UCB. Jose Matias Arbelo has received honoraria for educational presentations or clinical studies participation by Abbvie, UCB Pharma and Italfarmaco. Pablo Martinez-Martin has received honorarium from Editorial Viguera and Movement Disorder Society for lecturing in courses; from AbbVie for speaking in experts’ meetings and for participating in the Advisory Board of an epidemiological study. Grant: from the International Parkinson and Movement Disorder Society for the Pilot Study of the MDS-Non-Motor Symptoms Scale.

Informed consent

All patients and caregivers provided written informed consent.

Additional information

Members of the EDIS Study Group are listed in acknowledgements section.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 16 kb)

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Catalan, M.J., Molina-Arjona, J.A., Mir, P. et al. Improvement of impulse control disorders associated with levodopa–carbidopa intestinal gel treatment in advanced Parkinson’s disease. J Neurol 265, 1279–1287 (2018). https://doi.org/10.1007/s00415-018-8803-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-018-8803-1

Keywords

search

Navigation