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,to check access.
Access this article
Similar content being viewed by others
Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55:259–272
Takahashi H, Wakabayashi K (2001) The cellular pathology of Parkinson’s disease. Neuropathology 21:315–322
Obeso JA, Olanow CW, Nutt JG (2000) Levodopa motor complications in Parkinson’s disease. Trends Neurosci 23:S2–S7
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
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
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
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/10.1586/1473718.104.22.1683
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
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
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
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
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
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
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
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
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
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
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
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
Kazis LE, Anderson JJ, Meenan RF (1989) Effect sizes for interpreting changes in health status. Med Care 27:S178–S189
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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).
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.
All patients and caregivers provided written informed consent.
Members of the EDIS Study Group are listed in acknowledgements section.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
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