Drug Safety

, Volume 32, Issue 6, pp 475–488 | Cite as

Behavioural Adverse Effects of Dopaminergic Treatments in Parkinson’s Disease

Incidence, Neurobiological Basis, Management and Prevention
  • Angelo Antonini
  • Roberto Cilia
Review Article


Treatment of Parkinson’s disease has traditionally focused on the management of motor disability while behavioural disturbances have received less attention. Recently, impulse control disorders and aberrant repetitive behaviours have surged to clinical relevance as they occur during dopamine replacement treatment (mainly with dopamine agonists) and worsen patient and caregiver quality of life. Patients are unable to adequately estimate the negative consequences of their actions and are prone to entertain compulsive reward-seeking activities.

This review aims to summarize current evidence on the epidemiology of behavioural disturbances in Parkinson’s disease, recent insights into their neurobiological basis and to discuss strategies for management and prevention. Studies from 1990 through to December 2008 were retrieved via searches of the Cochrane Database of Systematic Reviews and PubMed.

The mechanisms underlying the development of behavioural disturbances in Parkinson’s disease are debated but current evidence points to specific risk factors: male sex, young age at onset, underlying personality traits characterized by high impulsivity and novelty seeking, and personal or family history of addictive disorders. Specifically, in predisposed individuals dopamine replacement therapy leads to overstimulation of dopamine receptors within the mesocorticolimbic pathways and in turn to the development of addictive behaviours, such as impulse control disorders and compulsive medication intake. Since these disturbances affect individuals who have often unremarkable psychiatric history and no cognitive impairment, their identification and management is complex. Compulsive medication intake (described as ‘hedonistic homeostatic dysregulation’ or ‘dopamine dysregulation syndrome’) is commonly associated with fluctuations in advanced disease, while impulse control disorders frequently occur in early Parkinson’s disease and within normal-range medication dosages.

Management primarily requires reduction of dopaminergic therapy but psychosocial support is often required. Use of selective serotonin reuptake inhibitors in the dose used for obsessive compulsive disorders may help, while benefit from atypical antipsychotics is limited in most cases. Deep brain stimulation should be considered with caution in these subjects. Prevention is based on the identification of at-risk individuals and active monitoring. Given the social and potentially medical-legal consequences of these behaviours, we encourage treating physicians to discuss risks with patients before treatment is initiated.


Deep Brain Stimulation Dopamine Agonist Pathological Gambling Iowa Gambling Task Addictive Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest to declare that are directly relevant to the content of this review.


  1. 1.
    Zesiewicz TA, Gold M, Chari G, et al. Current issues in depression in Parkinson’s disease. Am J Geriatr Psychiatry 1999; 7(2): 110–8PubMedGoogle Scholar
  2. 2.
    Antonini A, Colosimo C, Marconi R, et al. The PRIAMO study: background, methods and recruitment. Neurol Sci 2008; 29(2): 61–5PubMedGoogle Scholar
  3. 3.
    Molina JA, Sáinz-Artiga MJ, Fraile A, et al. Pathologic gambling in Parkinson’s disease: a behavioral manifestation of pharmacologic treatment? Mov Disord 2000; 15(5): 869–72PubMedGoogle Scholar
  4. 4.
    Giovannoni G, O’Sullivan JD, Turner K, et al. Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies. J Neurol Neurosurg Psychiatry 2000; 68(4): 423–8PubMedGoogle Scholar
  5. 5.
    Gschwandtner U, Aston J, Renaud S, et al. Pathological gambling in patients with Parkinson’s Disease. Clin Neuropharmacol 2001; 24: 170–2PubMedGoogle Scholar
  6. 6.
    Montastruc JL, Schmitt L, Bagheri H. Pathological gambling behavior in a patient with Parkinson’s disease treated with levodopa and bromocriptine. Rev Neurol (Paris) 2003; 159(4): 441–3Google Scholar
  7. 7.
    Driver-Dunckley E, Samanta J. Pathological gambling associated with dopamine agonist therapy in Parkinson’s disease. Neurology 2003; 61(3): 422–3PubMedGoogle Scholar
  8. 8.
    Avanzi M, Uber E, Bonfà F. Pathological gambling in two patients on dopamine replacement therapy for Parkinson’s disease. Neurol Sci 2004; 25: 98–101PubMedGoogle Scholar
  9. 9.
    Kurlan R. Disabling repetitive behaviors in Parkinson’s disease. Mov Disord 2004; 19(4): 433–69PubMedGoogle Scholar
  10. 10.
    Dodd ML, Klos KJ, Bower JH, et al. Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol 2005; 62(9): 1377–81PubMedGoogle Scholar
  11. 11.
    Klos KJ, Bower JH, Josephs KA, et al. Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson’s disease and multiple system atrophy. Parkinsonism Relat Disord 2005; 11: 381–6PubMedGoogle Scholar
  12. 12.
    Weintraub D, Siderowf AD, Potenza MN, et al. Association of dopamine agonist use with impulse control disorders in Parkinson disease. Arch Neurol 2006; 63(7): 969–73PubMedGoogle Scholar
  13. 13.
    Voon V, Hassan K, Zurowski M, et al. Prospective prevalence of pathologic gambling and medication association in Parkinson disease. Neurology 2006; 13(11): 1750–2Google Scholar
  14. 14.
    Voon V, Hassan K, Zurowski M, et al. Prevalence of repetitive and reward-seeking behaviors in Parkinson disease. Neurology 2006; 67(7): 1254–7PubMedGoogle Scholar
  15. 15.
    Grosset KA, Macphee G, Pal G, et al. Problematic gambling on dopamine agonists: not such a rarity. Mov Disord 2006; 21(12): 2206–8PubMedGoogle Scholar
  16. 16.
    Pontone G, Williams JR, Bassett SS, et al. Clinical features associated with impulse control disorders in Parkinson disease. Neurology 2006; 67(7): 1258–61PubMedGoogle Scholar
  17. 17.
    Imamura A, Uitti RJ, Wszolek ZK. Dopamine agonist therapy for Parkinson disease and pathological gambling. Parkinsonism Relat Disord 2006; 12(8): 506–8PubMedGoogle Scholar
  18. 18.
    Drapier D, Drapier S, Sauleau P, et al. Pathological gambling secondary to dopaminergic therapy in Parkinson’s disease. Psychiatry Res 2006; 144(2–3): 241–4PubMedGoogle Scholar
  19. 19.
    Nirenberg MJ, Waters C. Compulsive eating and weight gain related to dopamine agonist use. Mov Disord 2006; 21(4): 524–9PubMedGoogle Scholar
  20. 20.
    Voon V, Thomsen T, Miyasaki JM, et al. Factors associated with dopaminergic medication-related pathological gambling in Parkinson disease. Arch Neurol 2007; 64(2): 212–6PubMedGoogle Scholar
  21. 21.
    Wong SH, Cowen Z, Allen EA, et al. Internet gambling and other pathological gambling in Parkinson’s disease: a case series. Mov Disord 2007; 22(4): 591–3PubMedGoogle Scholar
  22. 22.
    Isaias IU, Siri C, Cilia R, et al. The relationship between impulsivity and impulse control disorders in Parkinson’s disease. Mov Disord 2008; 23(3): 411–5PubMedGoogle Scholar
  23. 23.
    Hollander E, Wong CM. Obsessive-compulsive spectrum disorders. J Clin Psychiatry 1995; 56 Suppl. 4: 3–6PubMedGoogle Scholar
  24. 24.
    Blaszczynski A. Pathological gambling and obsessive-compulsive spectrum disorders. Psychol Rep 1999; 84(1): 107–13PubMedGoogle Scholar
  25. 25.
    Holden C. ‘Behavioral’ addictions: do they exist? Science 2001; 294(5544): 980–2PubMedGoogle Scholar
  26. 26.
    Blanco C, Moreyra P, Nunes EV, et al. Pathological gambling: addiction or compulsion? Semin Clin Neuropsychiatry 2001; 6: 167–76PubMedGoogle Scholar
  27. 27.
    Grant JE, Potenza MN. Compulsive aspects of impulse-control disorders. Psychiatr Clin North Am 2006; 29(2): 539–51PubMedGoogle Scholar
  28. 28.
    Potenza MN. Should addictive disorders include non-substance-related conditions? Addiction 2006; 101 Suppl. 1: 142–51PubMedGoogle Scholar
  29. 29.
    Petry NM. Gambling and substance use disorders: current status and future directions. Am J Addict 2007; 16(1): 1–9PubMedGoogle Scholar
  30. 30.
    Moeller FG, Barratt ES, Dougherty DM, et al. Psychiatric aspects of impulsivity. Am J Psychiatry 2001; 158: 1783–93PubMedGoogle Scholar
  31. 31.
    Vitacco MJ, Rogers R. Predictors of adolescent psychopathy; the role of impulsivity, hyperactivity, and sensation seeking. J Am Acad Psychiatry Law 2001; 29: 374–82PubMedGoogle Scholar
  32. 32.
    Chambers RA, Taylor JR, Potenza MN. Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability. Am J Psychiatry 2003; 160(6): 1041–52PubMedGoogle Scholar
  33. 33.
    Koob GF, Ahmed SH, Boutrel B, et al. Neurobiological mechanisms in the transition from drug use to drug dependence. Neurosci Biobehav Rev 2004; 27(8): 739–49PubMedGoogle Scholar
  34. 34.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed., text revision. Washington, DC: American Psychiatric Association, 2000Google Scholar
  35. 35.
    Pallanti S, Quercioli L, Sood E, et al. Lithium and valproate treatment of pathological gambling: a randomized single-blind study. J Clin Psychiatry 2002; 63(7): 559–64PubMedGoogle Scholar
  36. 36.
    Voon V, Fox SH. Medication-related impulse control and repetitive behaviors in Parkinson disease. Arch Neurol 2007; 64(8): 1089–96PubMedGoogle Scholar
  37. 37.
    Gallagher DA, O’Sullivan SS, Evans AH, et al. Pathological gambling in Parkinson’s disease: risk factors and differences from dopamine dysregulation. An analysis of published case series. Mov Disord 2007; 22(12): 1757–63PubMedGoogle Scholar
  38. 38.
    Lu C, Bharmal A, Suchowersky O. Gambling and Parkinson disease [letter]. Arch Neurol 2006; 63(2): 298PubMedGoogle Scholar
  39. 39.
    Fox S. Dopamine receptor pharmacology and impulse control disorders in PD. Mov Disord 2008; 23(9) 1333–4Google Scholar
  40. 40.
    Avanzi M, Baratti M, Cabrini S, et al. Prevalence of pathological gambling in patients with Parkinson’s disease. Mov Disord 2006; 21: 2068–72PubMedGoogle Scholar
  41. 41.
    Lawrence AD, Evans AH, Lees AJ. Compulsive use of dopamine replacement therapy in Parkinson’s disease: reward systems gone awry? Lancet Neurol 2003; 2(10): 595–604PubMedGoogle Scholar
  42. 42.
    Weintraub D, Koester J, Potenza M, et al. Dopaminergic therapy and impulse control disorders in Parkinson’s disease: top line results of a cross-sectional study of over 3000 patients [abstract]. Mov Disord 2008; 23 Suppl. 4: 38Google Scholar
  43. 43.
    Shaffer HJ, Hall MN, Vander Bilt J. Estimating the prevalence of disordered gambling in the United States and Canada: a research synthesis. Am J Public Health 1999; 89: 1369–76PubMedGoogle Scholar
  44. 44.
    Morasco BJ, Vom Eigen KA, Petry NM. Severity of gambling is associated with physical and emotional health in urban primary care patients. Gen Hosp Psychiatry 2006; 28: 94–100PubMedGoogle Scholar
  45. 45.
    Potenza MN, Fiellin DA, Heninger GR, et al. Gambling: an addictive behavior with health and primary care implications. J Gen Intern Med 2002; 17(9): 721–32PubMedGoogle Scholar
  46. 46.
    Evans AH, Lawrence AD, Potts J, et al. Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson disease. Neurology 2005; 65(10): 1570–4PubMedGoogle Scholar
  47. 47.
    Grant JE, Levine L, Kim D, et al. Impulse control disorders in adult psychiatric inpatients. Am J Psychiatry 2005; 162(1): 2184–8PubMedGoogle Scholar
  48. 48.
    Javoy-Agid F, Agid Y. Is the mesocortical dopaminergic system involved in Parkinson’s disease? Neurology 1980; 30: 1326–30PubMedGoogle Scholar
  49. 49.
    Ouchi Y, Yoshikawa E, Okada H, et al. Alterations in binding site density of dopamine transporter in the striatum, orbitofrontal cortex, and amygdala in early Parkinson’s disease: compartment analysis for β-CFT binding with positron emission tomography. Ann Neurol 1999; 45: 601–10PubMedGoogle Scholar
  50. 50.
    Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science 1997; 275: 1593–9PubMedGoogle Scholar
  51. 51.
    Frank MJ, Seeberger LC, O’Reilly RC. By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science 2004; 306(5703): 1940–3PubMedGoogle Scholar
  52. 52.
    Girault JA, Greengard P. The neurobiology of dopamine signaling. Arch Neurol 2004; 61(5): 641–4PubMedGoogle Scholar
  53. 53.
    Schultz W. Behavioral dopamine signals. Trends Neurosci 2007; 30(5): 203–10PubMedGoogle Scholar
  54. 54.
    Volkow ND, Fowler JS, Wang GJ, et al. Dopamine in drug abuse and addiction: results of imaging studies and treatment implications. Arch Neurol 2007; 64(11): 1575–9PubMedGoogle Scholar
  55. 55.
    Künig G, Leenders KL, Martin-Sölch C, et al. Reduced reward processing in the brains of Parkinsonian patients. Neuroreport 2000; 11(17): 3681–7PubMedGoogle Scholar
  56. 56.
    Czernecki V, Pillon B, Houeto JL, et al. Motivation, reward, and Parkinson’s disease: influence of dopatherapy. Neuropsychologia 2002; 40(13): 2257–67PubMedGoogle Scholar
  57. 57.
    Goerendt IK, Lawrence AD, Brooks DJ. Reward processing in health and Parkinson’s disease: neural organization and reorganization. Cereb Cortex 2004; 14(1): 73–80PubMedGoogle Scholar
  58. 58.
    Kulisevsky J, Avila A, Barbanoj M, et al. Acute effects of levodopa on neuropsychological performance in stable and fluctuating Parkinson’s disease patients at different levodopa plasma levels. Brain 1996; 119: 2121–32PubMedGoogle Scholar
  59. 59.
    Frank MJ. Dynamic dopamine modulation in the basal ganglia: a neurocomputational account of cognitive deficits in medicated and nonmedicated Parkinsonism. J Cogn Neurosci 2005; 17(1): 51–72PubMedGoogle Scholar
  60. 60.
    Cools R. Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson’s disease. Neurosci Biobehav Rev 2006; 30(1): 1–23PubMedGoogle Scholar
  61. 61.
    Cools R, Barker RA, Sahakian BJ, et al. L-Dopa medication remediates cognitive inflexibility, but increases impulsivity in patients with Parkinson’s disease. Neuropsychologia 2003; 41(11): 1431–41PubMedGoogle Scholar
  62. 62.
    Cools R, Lewis SJ, Clark L, et al. L-DOPA disrupts activity in the nucleus accumbens during reversal learning in Parkinson’s disease. Neuropsychopharmacology 2007; 32(1): 180–9PubMedGoogle Scholar
  63. 63.
    Dagher A, Robbins TW. Personality, addiction, dopamine: insights from Parkinson’s disease. Neuron 2009; 61: 502–10PubMedGoogle Scholar
  64. 64.
    Voon V, Pessiglione M, Brezing C, et al. Dopamine agonist-induced gambling and shopping is associated with enhanced reward learning mediated via dopaminergic ventral striatal prediction error teaching signal [abstract]. Mov Disord 2008; 23 Suppl. 14: 35Google Scholar
  65. 65.
    Robinson TE, Berridge KC. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 1993; 18: 247–91PubMedGoogle Scholar
  66. 66.
    Hyman SE. Addiction: a disease of learning and memory. Am J Psychiatry 2005; 162(8): 1414–22PubMedGoogle Scholar
  67. 67.
    Bechara A, Damasio AR, Damasio H, et al. Insensitivity to future consequences following damage to human pre-frontal cortex. Cognition 1994; 50: 7–15PubMedGoogle Scholar
  68. 68.
    Alessi SM, Petry NM. Pathological gambling severity is associated with impulsivity in a delay discounting procedure. Behav Processes 2003; 64(3): 345–54PubMedGoogle Scholar
  69. 69.
    Hariri AR, Brown SM, Williamson DE, et al. Preference for immediate over delayed rewards is associated with magnitude of ventral striatal activity. J Neurosci 2006; 26(51): 13213–7PubMedGoogle Scholar
  70. 70.
    Fukui H, Murai T, Fukuyama H, et al. Functional activity related to risk anticipation during performance of the Iowa Gambling Task. Neuroimage 2005; 24(1): 253–9PubMedGoogle Scholar
  71. 71.
    Pagonabarraga J, Kulisevsky J, Llebaria G, et al. Parkinson’s disease-cognitive rating scale: a new cognitive scale specific for Parkinson’s disease. Mov Disord 2008; 23(7): 998–1005PubMedGoogle Scholar
  72. 72.
    Cilia R, Siri C, Marotta G, et al. Functional abnormalities underlying pathological gambling in Parkinson’s disease. Arch Neurol 2008; 65: 1604–11PubMedGoogle Scholar
  73. 73.
    Tippmann-Peikert M, Park JG, Boeve BF, et al. Pathologic gambling in patients with restless legs syndrome treated with dopaminergic agonists. Neurology 2007; 68(4): 301–3PubMedGoogle Scholar
  74. 74.
    Evans AH, Butzkueven H. Dopamine agonist-induced pathological gambling in restless legs syndrome due to multiple sclerosis. Mov Disord 2007; 22(4): 590–1PubMedGoogle Scholar
  75. 75.
    Wang GJ, Yang J, Volkow ND, et al. Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry. Proc Natl Acad Sci USA 2006; 103(42): 15641–5PubMedGoogle Scholar
  76. 76.
    Beaver JD, Lawrence AD, van Ditzhuijzen J, et al. Individual differences in reward drive predict neural responses to images of food. J Neurosci 2006; 26(19): 5160–6PubMedGoogle Scholar
  77. 77.
    Marinelli M, White FJ. Enhanced vulnerability to cocaine self-administration is associated with elevated impulse activity of midbrain dopamine neurons. J Neurosci 2000; 20(23): 8876–85PubMedGoogle Scholar
  78. 78.
    Kalivas PW, Volkow ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 2005; 162(8): 1403–13PubMedGoogle Scholar
  79. 79.
    Mamikonyan E, Siderowf AD, Duda JE, et al. Long-term follow-up of impulse control disorders in Parkinson’s disease. Mov Disord 2008; 23(1): 75–80PubMedGoogle Scholar
  80. 80.
    Riley DE. Reversible transvestic fetishism in a man with Parkinson’s disease treated with selegiline. Clin Neuropharmacol 2002; 25(4): 234–7PubMedGoogle Scholar
  81. 81.
    Shapiro MA, Chang YL, Munson SK, et al. Hypersexuality and paraphilia induced by selegiline in Parkinson’s disease: report of 2 cases. Parkinsonism Relat Disord 2006; 12(6): 392–5PubMedGoogle Scholar
  82. 82.
    Witjas T, Baunez C, Henry JM, et al. Addiction in Parkinson’s disease: impact of subthalamic nucleus deep brain stimulation. Mov Disord 2005; 20(8): 1052–5PubMedGoogle Scholar
  83. 83.
    Ardouin C, Voon V, Worbe Y, et al. Pathological gambling in Parkinson’s disease improves on chronic subthalamic nucleus stimulation. Mov Disord 2006; 21(11): 1941–6PubMedGoogle Scholar
  84. 84.
    Bandini F, Primavera A, Pizzorno M, et al. DBS and medication reduction as a strategy to treat pathological gambling in Parkinson’s disease. Parkinsonism Relat Disord 2007; 13(6): 369–71PubMedGoogle Scholar
  85. 85.
    Knobel D, Aybek S, Pollo C, et al. Rapid resolution of dopamine dysregulation syndrome (DDS) after subthalamic DBS for Parkinson disease (PD): a case report. Cogn Behav Neurol 2008 Sep; 21(3): 187–9PubMedGoogle Scholar
  86. 86.
    Romito LM, Raja M, Daniele A, et al. Transient mania with hypersexuality after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson’s disease. Mov Disord 2002; 17(6): 1371–4PubMedGoogle Scholar
  87. 87.
    Houeto JL, Mesnage V, Mallet L, et al. Behavioural disorders: Parkinson’s disease and subthalamic stimulation. J Neurol Neurosurg Psychiatry 2002; 72: 701–7PubMedGoogle Scholar
  88. 88.
    Morgan JC, diDonato CJ, Iyer SS, et al. Self-stimulatory behavior associated with deep brain stimulation in Parkinson’s disease. Mov Disord 2006; 21: 283–5PubMedGoogle Scholar
  89. 89.
    Smeding HM, Goudriaan AE, Foncke EM, et al. Pathological gambling after bilateral subthalamic nucleus stimulation in Parkinson disease. J Neurol Neurosurg Psychiatry 2007; 78(5): 517–9PubMedGoogle Scholar
  90. 90.
    Absher JR, Vogt BA, Clark DG, et al. Hypersexuality and hemiballism due to subthalamic infarction. Neuropsychiatry Neuropsychol Behav Neurol 2000; 13: 220–9PubMedGoogle Scholar
  91. 91.
    Baunez C, Amalric M, Robbins TW. Enhanced food-related motivation after bilateral lesions of the subthalamic nucleus. J Neurosci 2002; 22(2): 562–8PubMedGoogle Scholar
  92. 92.
    Frank MJ, Samanta J, Moustafa AA, et al. Hold your horses: impulsivity, deep brain stimulation, and medication in parkinsonism. Science 2007; 318(5854): 1309–12PubMedGoogle Scholar
  93. 93.
    Roane DM, Yu M, Feinberg TE, et al. Hypersexuality after pallidal surgery in Parkinson disease. Neuropsychiatry Neuropsychol Behav Neurol 2002; 15(4): 247–51PubMedGoogle Scholar
  94. 94.
    Mendez MF, O’Connor SM, Lim GT. Hypersexuality after right pallidotomy for Parkinson’s disease. J Neuropsychiatry Clin Neurosci 2004; 16(1): 37–40PubMedGoogle Scholar
  95. 95.
    Burkhard PR, Vingerhoets FJ, Berney A, et al. Suicide after successful deep brain stimulation for movement disorders. Neurology 2004; 63(11): 2170–2PubMedGoogle Scholar
  96. 96.
    Grant JE, Potenza MN. Impulse control disorders: clinical characteristics and pharmacological management. Ann Clin Psychiatry 2004; 16(1): 27–34PubMedGoogle Scholar
  97. 97.
    Hollander E, DeCaria CM, Finkell JN, et al. A randomized double blind fluvoxamine/placebo crossover trial in pathological gambling. Biol Psychiatry 2000; 47(9): 813–7PubMedGoogle Scholar
  98. 98.
    Blanco C, Petkova E, Ibanez A, et al. A pilot placebo-controlled study of fluvoxamine for pathological gambling. Ann Clin Psychiatry 2002; 14(1): 9–15PubMedGoogle Scholar
  99. 99.
    Kim SW, Grant JE, Adson DE, et al. A double-blind placebo-controlled study of the efficacy and safety of paroxetine in the treatment of pathological gambling. J Clin Psychiatry 2002; 63(6): 501–7PubMedGoogle Scholar
  100. 100.
    Grant JE, Kim SW, Potenza MN, et al. Paroxetine treatment of pathological gambling: a multi-center randomized controlled trial. Int Clin Psychopharmacol 2003; 18(4): 243–9PubMedGoogle Scholar
  101. 101.
    Saiz-Ruiz J, Blanco C, Ibanez A, et al. Sertraline treatment of pathological gambling: a pilot study. J Clin Psychiatry 2005; 66(1): 28–33PubMedGoogle Scholar
  102. 102.
    Grant JE, Potenza MN. Escitalopram treatment of pathological gambling with co-occurring anxiety: an open-label pilot study with double-blind discontinuation. Int Clin Psychopharmacol 2006; 21(4): 203–9PubMedGoogle Scholar
  103. 103.
    Black DW, Shaw M, Forbush KT, et al. An open-label trial of escitalopram in the treatment of pathological gambling. Clin Neuropharmacol 2007; 30(4): 206–12PubMedGoogle Scholar
  104. 104.
    Mitchell JE, de Zwaan M, Roerig JL. Drug therapy for patients with eating disorders. Curr Drug Targets CNS Neurol Disord 2003; 2(1): 17–29PubMedGoogle Scholar
  105. 105.
    Wilfley DE, Crow SJ, Hudson JI, et al. Sibutramine Binge Eating Disorder Research Group. Efficacy of sibutramine for the treatment of binge eating disorder: a randomized multicenter placebo-controlled double-blind study. Am J Psychiatry 2008; 165(1): 51–8PubMedGoogle Scholar
  106. 106.
    Hollander E, Pallanti S, Allen A, et al. Does sustained-release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders? Am J Psychiatry 2005; 162(1): 137–45PubMedGoogle Scholar
  107. 107.
    Rogers R, Goodwin G. Lithium may reduce gambling severity in pathological gamblers with bipolar disorder [letter]. Evid Based Ment Health 2005; 8(3): 80PubMedGoogle Scholar
  108. 108.
    Dannon PN. Topiramate for the treatment of kleptomania: a case series and review of the literature. Clin Neuropharmacol 2003; 26(1): 1–4PubMedGoogle Scholar
  109. 109.
    Grant JE. Understanding and treating kleptomania: new models and new treatments. Isr J Psychiatry Relat Sci 2006; 43(2): 81–7PubMedGoogle Scholar
  110. 110.
    Nicolato R, Romano-Silva MA, Correa H, et al. Lithium and topiramate association in the treatment of comorbid pathological gambling and bipolar disorder [letter]. Aust N Z J Psychiatry 2007; 41(7): 628PubMedGoogle Scholar
  111. 111.
    Kim SW, Grant JE, Adson DE, et al. Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling. Biol Psychiatry 2001; 49: 914–21PubMedGoogle Scholar
  112. 112.
    Ikemoto S, Glazier BS, Murphy JM, et al. Role of dopamine D1 and D2 receptors in the nucleus accumbens in mediating reward. J Neurosci 1997; 17: 8580–7PubMedGoogle Scholar
  113. 113.
    Kim SW. Opioid antagonists in the treatment of impulse-control disorders. J Clin Psychiatry 1998; 59(4): 159–62PubMedGoogle Scholar
  114. 114.
    Grant JE, Potenza MN, Hollander E, et al. A multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. Am J Psychiatry 2006; 163(12): 303–12PubMedGoogle Scholar
  115. 115.
    Fong T, Kalechstein A, Bernhard B, et al. A double-blind, placebo-controlled trial of olanzapine for the treatment of video poker pathological gamblers. Pharmacol Biochem Behav 2008; 89(3): 298–303PubMedGoogle Scholar
  116. 116.
    McElroy SL, Nelson EB, Welge JA, et al. Olanzapine in the treatment of pathological gambling: a negative randomized placebo-controlled trial. J Clin Psychiatry 2008; 69(3): 433–40PubMedGoogle Scholar
  117. 117.
    Gebhardt S, Haberhausen M, Krieg JC, et al. Clozapine/ olanzapine-induced recurrence or deterioration of binge eating-related eating disorders. J Neural Transm 2007; 114(8): 1091–5PubMedGoogle Scholar
  118. 118.
    Kluge M, Schuld A, Himmerich H, et al. Clozapine and olanzapine are associated with food craving and binge eating: results from a randomized double-blind study. J Clin Psychopharmacol 2007; 27(6): 662–6PubMedGoogle Scholar
  119. 119.
    Seedat S, Kesler S, Niehaus DJ, et al. Pathological gambling behaviour: emergence secondary to treatment of Parkinson’s disease with dopaminergic agents. Depress Anxiety 2000; 11(4): 185–6PubMedGoogle Scholar
  120. 120.
    Sevincok L, Akoglu A, Akyol A. Quetiapine in a case with Parkinson disease and pathological gambling. J Clin Psychopharmacol 2007; 27(1): 107–8PubMedGoogle Scholar
  121. 121.
    Trosch RM, Friedman JH, Lannon MC, et al. Clozapine use in Parkinson’s disease: a retrospective analysis of a large multicentered clinical experience. Mov Disord 1998; 13(3): 377–82PubMedGoogle Scholar
  122. 122.
    Fernandez HH, Durso R. Clozapine for dopaminergic-induced paraphilias in Parkinson’s disease. Mov Disord 1998; 13(3): 597–8PubMedGoogle Scholar
  123. 123.
    McFarland K, Lapish CC, Kalivas PW. Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 2003; 23(8): 3531–7PubMedGoogle Scholar
  124. 124.
    Baker DA, McFarland K, Lake RW, et al. N-acetyl cysteine-induced blockade of cocaine-induced reinstatement. Ann N Y Acad Sci 2003; 1003: 349–51PubMedGoogle Scholar
  125. 125.
    LaRowe SD, Mardikian P, Malcolm R, et al. Safety and tolerability of N-acetylcysteine in cocaine-dependent individuals. Am J Addict 2006; 15: 105–10PubMedGoogle Scholar
  126. 126.
    Grant JE, Kim SW, Odlaug BL. N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry 2007; 62(6): 652–7PubMedGoogle Scholar
  127. 127.
    Oakley-Browne MA, Adams P, Mobberley PM. Withdrawn: interventions for pathological gambling. Cochrane Database Syst Rev 2007; (1): CD001521Google Scholar
  128. 128.
    Toneatto T, Dragonetti R. Effectiveness of community-based treatment for problem gambling: a quasi-experimental evaluation of cognitive-behavioral versus twelve-step therapy. Am J Addict 2008; 17(4): 298–303PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Parkinson InstituteIstituti Clinici di PerfezionamentoMilanItaly
  2. 2.Department of NeurologyUniversity of Milan-Bicocca, San Gerardo HospitalMonzaItaly

Personalised recommendations