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Spectrum of addictions in Parkinson’s disease: from dopamine dysregulation syndrome to impulse control disorders

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Abstract

There is an increasing awareness that addictive disorders may occur in Parkinson’s disease (PD), either typical substance-related addictions that are commonly known as dopamine dysregulation syndrome (DDS) or behavioral addictive syndromes, usually presenting as impulse control disorders (ICDs) that include pathological gambling, hypersexuality, compulsive eating and buying. DDS is characterized by the use of dopaminergic drugs in doses larger than those required to treat motor symptoms, despite the development of disabling dyskinesias. Case reporting and prospective studies have reported an association between ICDs and the use of dopamine-agonists (DAs) at greater doses, while DDS has been associated with levodopa at greater doses or short-acting DAs. Risk factors for addictions in PD include male sex, younger age or younger age at PD onset, history of substance use or bipolar disorder, and a personality profile characterized by impulsiveness. Functional neuroimaging studies such as functional MRI and PET have investigated in vivo the neurobiological basis of these pathologic behaviors. The management for clinically significant ICD symptoms should consist of modifications to dopamine replacement therapy (DRT), particularly DAs, which is usually associated with an improvement of ICDs, whereas there is no empiric evidence supporting the use of psychiatric drugs in ICDs in PD. Management of DDS is not easy, mainly because balancing the drugs in the long term could represent a difficult problem. Hypomanic and psychotic episodes are best managed with a reduction of DRT performed in hospital also by using atypical antipsychotics low dose.

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References

  1. Jaffe JH (2001) Goodman and Gilman’s the pharmacological basis of therapeutics. In: Gilman AG, Rall TW, Nies AS, Taylor P (eds) 8th edn. Pergamon, New York, pp 522–573

  2. World Health Organization (1990) International statistical classification of diseases and related health problems—10th revision, World Health Organization, Geneva

  3. Spanagel R, Heilig M (2005) Addiction and its brain science. Addiction 100(12):1813–1822

    Article  PubMed  Google Scholar 

  4. Heidbreder CA, Gardner EL, Xi ZX, Thanos PK, Mugnaini M, Hagan JJ et al (2005) The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence. Brain Res Rev 49(1):77–105

    Article  CAS  PubMed  Google Scholar 

  5. Bressan RA, Crippa JA (2005) The role of dopamine in reward and pleasure behaviour—review of data from preclinical research. Acta Psychiatr Scand Suppl 427:14–21

    Article  PubMed  Google Scholar 

  6. Koepp MJ, Gunn RN, Lawrence AD, Cunningham VJ, Dagher A, Jones T et al (1998) Evidence for striatal dopamine release during a video game. Nature 393:266–268

    Article  CAS  PubMed  Google Scholar 

  7. Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278(5335):52–58

    Article  CAS  PubMed  Google Scholar 

  8. Robinson TE, Berridge KC (2000) The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95(Suppl. 2):S91–S117

    PubMed  Google Scholar 

  9. Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24(2):97–129

    Article  CAS  PubMed  Google Scholar 

  10. Giovannoni G, O’Sullivan JD, Turner K, Manson AJ, Lees AJ (2000) Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies. J Neurol Neurosurg Psychiatry 68:423–428

    Article  CAS  PubMed  Google Scholar 

  11. Evans AH, Katzenschlager R, Paviour D, O’Sullivan JD, Appel S, Lawrence AD, Lees AJ (2004) Punding in Parkinson’s disease: its relation to the dopamine dysregulation syndrome. Mov Disord 19:397–405

    Article  PubMed  Google Scholar 

  12. Miyasaki JM, Al Hassan K, Lang AE, Voon V (2007) Punding prevalence in Parkinson’s disease. Mov Disord 22(8):1179–1181

    Article  PubMed  Google Scholar 

  13. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington

    Google Scholar 

  14. Weintraub D (2008) Dopamine and impulse control disorders in Parkinson’s disease. Ann Neurol 64(Suppl 2):S93–S100

    PubMed  Google Scholar 

  15. Holden C (2001) ‘Behavioral’ addictions: do they exist? Science 294:980–982

    Article  CAS  PubMed  Google Scholar 

  16. Tamminga CA, Nestler EJ (2006) Pathological gambling: focusing on the addiction, not the activity. Am J Psychiatry 163:303–312

    Article  Google Scholar 

  17. Brewer JA, Potenza MN (2008) The neurobiology and genetics of impulse control disorders: relationships to drug addictions. Biochem Pharmacol 75:63–75

    Article  CAS  PubMed  Google Scholar 

  18. Hollander E, Allen A (2006) Is compulsive buying a real disorder, and is it really compulsive? Am J Psychiatry 163:1670–1672

    Article  PubMed  Google Scholar 

  19. Pezzella FR, Colosimo C, Vanacore N, Di Rezze S, Chianese M, Fabbrini G et al (2005) Prevalence and clinical features of hedonistic homeostatic dysregulation in Parkinson’s disease. Mov Disord 20(1):77–81

    Article  PubMed  Google Scholar 

  20. Giladi N, Weitzman N, Schreiber S, Shabtai H, Peretz C (2007) New-onset heightened interest or drive for gambling, shopping, eating, or sexual activity in patients with Parkinson’s disease: the role of dopamine agonist treatment and age at motor symptoms onset. J Psychopharmacol 21:501–506

    Article  PubMed  Google Scholar 

  21. Driver-Dunckley E, Samanta J, Stacy M (2003) Pathological gambling associated with dopamine agonist therapy in Parkinson’s disease. Neurology 61:422–423

    CAS  PubMed  Google Scholar 

  22. Lu C, Bharmal A, Suchowersky O (2006) Gambling and Parkinson’s disease. Arch Neurol 63:298

    Article  PubMed  Google Scholar 

  23. Grosset KA, Macphee G, Pal G, Stewart D, Watt A, Davie J, Grosset DG (2006) Problematic gambling on dopamine agonists: not such a rarity. Mov Disord 21:2206–2208

    Article  PubMed  Google Scholar 

  24. Voon V, Hassan K, Zurowski M, Duff-Canning S, de Souza M, Fox S, Lang AE, Miyasaki J (2006) Prospective prevalence of pathological gambling and medication association in Parkinson disease. Neurology 66:1750–1752

    Article  CAS  PubMed  Google Scholar 

  25. Weintraub D, Siderowf AD, Potenza MN, Goveas J, Morales KH, Duda JE, Moberg PJ, Stern MB (2006) Association of dopamine agonist use with impulse control disorders in Parkinson disease. Arch Neurol 63:969–973

    Article  PubMed  Google Scholar 

  26. Voon V, Hassan K, Zurowski M, de Souza M, Thomsen T, Fox S, Lang AE, Miyasaki J (2006) Prevalence of repetitive and reward-seeking behaviors in Parkinson disease. Neurology 67:1254–1257

    Article  CAS  PubMed  Google Scholar 

  27. Isaias IU, Siri C, Cilia R, De Gaspari D, Pezzoli G, Antonini A (2008) The relationship between impulsivity and impulse control disorders in Parkinson’s disease. Mov Disord 23:411–415

    Article  PubMed  Google Scholar 

  28. Christenson GA, Faber RJ, deZwaan M (1994) Compulsive buying: descriptive characteristics and psychiatric comorbidity. J Clin Psychiatry 55:5–11

    CAS  PubMed  Google Scholar 

  29. Crockford D, Quickfall J, Currie S, Furtado S, Suchowersky O, El-Guebaly N (2008) Prevalence of problem and pathological gambling in Parkinson’s disease. J Gambl Stud 24(4):411–422

    Article  PubMed  Google Scholar 

  30. Avanzi M, Baratti M, Cabrini S, Bonfà F, Brighetti G, Uber E (2006) Prevalence of pathological gambling in patients with Parkinson’s disease. Mov Disord 21:2068–2072

    Article  PubMed  Google Scholar 

  31. Ceravolo R, Frosini D, Rossi C, Nicoletti V, Berti C, Unti E, et al. (2009) Prevalence of Impulse control disorders in Parkinson’s disease. Neurol Sci 30(Suppl):S456

    Google Scholar 

  32. Vogel HP, Shiffer R (1983) Hypersexuality: a complication of dopaminergic therapy in Parkinson’s disease. Pharmacopsychiatria 16:107–110

    Article  CAS  PubMed  Google Scholar 

  33. Harvey NS (1988) Serial cognitive profiles in levodopa-induced hypersexuality. Br J Psychiatry 153:833–836

    Article  CAS  PubMed  Google Scholar 

  34. Uitti RJ, Tanner CM, Rajput AH, Goetz CG, Klawans HL, Thiessen B (1989) Hypersexuality with antiparkinsonian therapy. Clin Neuropharmacol 12:375–383

    Article  CAS  PubMed  Google Scholar 

  35. O’Sullivan JD, Hughes AJ (1998) Apomorphine-induced penile erections in Parkinson’s disease. Mov Disord 13:536–539

    Article  PubMed  Google Scholar 

  36. Klos KJ, Bower JH, Josephs KA, Matsumoto JY, Ahlskog JE (2005) Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson’s disease and multiple system atrophy. Parkinsonism Relat Disord 11:381–386

    Article  PubMed  Google Scholar 

  37. Lawrence AD, Evans AH, Lees AJ (2003) Compulsive use of dopamine replacement therapy in Parkinson’s disease: reward systems gone awry? Lancet Neurol 2(10):595–604

    Article  CAS  PubMed  Google Scholar 

  38. Bearn J, Evans A, Kelleher M, Turner K, Lees A (2004) Recognition of a dopamine replacement therapy dependence syndrome in Parkinson’s disease: a pilot study. Drug Alcohol Depend 76(3):305–310

    Article  CAS  PubMed  Google Scholar 

  39. Gallagher DA, O’Sullivan SS, Evans AH, Lees AJ, Schrag A (2007) Pathological gambling in Parkinson’s disease: risk factors and differences from dopamine dysregulation. Mov Disord 22:1757–1763

    Article  PubMed  Google Scholar 

  40. Evans AH, Lawrence AD, Potts J, Appel S, Lees AJ (2005) Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson disease. Neurology 65:1570–1574

    Article  CAS  PubMed  Google Scholar 

  41. Singh A, Kandimala G, Dewey RB Jr, O’Suilleabhain P (2007) Risk factors for pathologic gambling and other compulsions among Parkinson’s disease patients taking dopamine agonists. J Clin Neurosci 14:1178–1181

    Article  CAS  PubMed  Google Scholar 

  42. Voon V, Thomsen T, Miyasaki JM, de Souza M, Shafro A, Fox SH, Duff-Canning S, Lang AE, Zurowski M (2007) Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease. Arch Neurol 64:212–216

    Article  PubMed  Google Scholar 

  43. Pontone G, Williams JR, Bassett SS, Marsh L (2006) Clinical features associated with impulse control disorders in Parkinson disease. Neurology 67:1258–1261

    Article  PubMed  Google Scholar 

  44. Santangelo G, Vitale C, Trojano L, Verde F, Grossi D, Barone P (2009) Cognitive dysfunctions and pathological gambling in patients with Parkinson’s disease. Mov Disord 24(6):899–905

    Article  PubMed  Google Scholar 

  45. Dodd ML, Klos KJ, Bower JH, Geda YE, Josephs KA, Ahlskog JE (2005) Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol 62:1377–1381

    Article  PubMed  Google Scholar 

  46. Driver-Dunckley ED, Noble BN, Hentz JG, Evidente VG, Caviness JN, Parish J, Krahn L, Adler CH (2007) Gambling and increased sexual desire with dopaminergic medications in restless legs syndrome. Clin Neuropharmacol 30(5):249–255

    Article  CAS  PubMed  Google Scholar 

  47. Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Comings DE (1995) Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. Pharmacogenetics 5(3):121–141

    Article  CAS  PubMed  Google Scholar 

  48. Comings DE, Gonzalez N, Wu S, Gade R, Muhleman D, Saucier G, Johnson P, Verde R, Rosenthal RJ, Lesieur HR, Rugle LJ, Miller WB, MacMurray JP (1999) Studies of the 48 bp repeat polymorphism of the DRD4 gene in impulsive, compulsive, addictive behaviors: Tourette syndrome, ADHD, pathological gambling, and substance abuse. Am J Med Genet 88(4):358–368

    Article  CAS  PubMed  Google Scholar 

  49. Pérez de Castro I, Ibáñez A, Torres P, Sáiz-Ruiz J, Fernández-Piqueras J (1997) Genetic association study between pathological gambling and a functional DNA polymorphism at the D4 receptor gene. Pharmacogenetics 7(5):345–348

    PubMed  Google Scholar 

  50. Lee JY, Lee EK, Park SS, Lim JY, Kim HJ, Kim JS, Jeon BS (2009) Association of DRD3 and GRIN2B with impulse control and related behaviors in Parkinson’s disease. Mov Disord 24:1803–1810

    Article  PubMed  Google Scholar 

  51. 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(5):852–858

    Article  CAS  PubMed  Google Scholar 

  52. Reuter J, Raedler T, Rose M, Hand I, Gläscher J, Büchel C (2005) Pathological gambling is linked to reduced activation of the mesolimbic reward system. Nat Neurosci 8(2):147–148

    Article  CAS  PubMed  Google Scholar 

  53. Cilia R, Siri C, Marotta G, Isaias IU, De Gaspari D, Canesi M, Pezzoli G, Antonini A (2008) Functional abnormalities underlying pathological gambling in Parkinson disease. Arch Neurol 65(12):1604–1611

    Article  PubMed  Google Scholar 

  54. Steeves TD, Miyasaki J, Zurowski M, Lang AE, Pellecchia G, Van Eimeren T, Rusjan P, Houle S, Strafella AP (2009) Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study. Brain 132:1376–1385

    Article  CAS  PubMed  Google Scholar 

  55. Frosini D, Pesaresi I, Rossi C, De Feo P, Cosottini M, Bonuccelli U, Ceravolo R (2009) Parkinson’s disease and pathological gambling: results from a fMRI study invesigating cue-induced brain activity. Parkinsonism Rel Dis 15(2):S52

    Article  Google Scholar 

  56. Mamikonyan E, Siderowf AD, Duda JE, Potenza MN, Horn S, Stern MB, Weintraub D (2008) Long-term follow-up of impulse control disorders in Parkinson’s disease. Mov Disord 23:75–80

    Article  PubMed  Google Scholar 

  57. Jimenez-Jimenez FJ, Sayed Y, Garcia-Soldevilla MA, Barcenilla B (2002) Possible zoophilia associated with dopaminergic therapy in Parkinson disease. Ann Pharmacother 36:1178–1179

    Article  PubMed  Google Scholar 

  58. Gschwandtner U, Aston J, Renaud S, Fuhr P (2001) Pathologic gambling in patients with Parkinson’s disease. Clin Neuropharmacol 24:170–172

    Article  CAS  PubMed  Google Scholar 

  59. Grant JE, Potenza MN (2004) Impulse control disorders: clinical characteristics and pharmacological management. Ann Clin Psychiatry 16:27–34

    PubMed  Google Scholar 

  60. Grant JE, Potenza MN, Hollander E, Cunningham-Williams R, Nurminen T, Smits G, Kallio A (2006) Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. Am J Psychiatry 163:303–312

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosciences, University of Pisa, Via Roma 67, 56126, Pisa, Italy

    Roberto Ceravolo, Daniela Frosini, Carlo Rossi & Ubaldo Bonuccelli

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  1. Roberto Ceravolo
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  2. Daniela Frosini
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  3. Carlo Rossi
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  4. Ubaldo Bonuccelli
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Correspondence to Roberto Ceravolo.

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Ceravolo, R., Frosini, D., Rossi, C. et al. Spectrum of addictions in Parkinson’s disease: from dopamine dysregulation syndrome to impulse control disorders. J Neurol 257 (Suppl 2), 276–283 (2010). https://doi.org/10.1007/s00415-010-5715-0

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