Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual behavior, and eating, are a serious and increasingly recognized complication of dopamine replacement therapy in Parkinson’s disease (PD). Other impulsive-compulsive behaviors have been linked to dopaminergic medications; these include punding (stereotyped, repetitive, purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive medication overuse). ICDs have been most closely related to the use of dopamine agonists (DAs), particularly at higher dosages; in contrast, DDS is primarily associated with shorter-acting, higher-potency dopaminergic medications, such as apomorphine and levodopa. Risk factors for ICDs may include male sex; younger age; younger age at PD onset; a pre-PD history of ICD(s); personal or family history of substance abuse; bipolar disorder; gambling problems; and impulsive personality traits. The primary treatment of ICDs in PD is discontinuation of DA therapy. Not all patients can tolerate this, however, due to worsening motor symptoms and/or DA withdrawal syndrome (a severe, stereotyped drug withdrawal syndrome similar to that of other psychostimulants). While psychiatric medications are frequently used to treat ICDs in the general population, there is no empirical evidence to suggest that they are effective in PD. Given the paucity of treatment options and potentially serious consequences of ICDs in PD, it is critical for patients to be monitored closely for their development. As empirically validated treatments for ICDs emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.

Keywords:
Compulsive behavior, D3 receptor, Dopamine agonist, Dopamine agonist withdrawal syndrome, Dopamine dysregulation syndrome, Impulse control disorder, Impulsive-compulsive behavior, Mesocorticolimbic, Parkinson’s disease, Pathological gambling
1.
Holden C: ‘Behavioral’ addictions: do they exist? Science 2001;294:980–982.
2.
Dagher A, Robbins TW: Personality, addiction, dopamine: insights from Parkinson’s disease. Neuron 2009;61:502–510.
3.
Voon V, Fox SH: Medication-related impulse control and repetitive behaviors in Parkinson disease. Arch Neurol 2007;64:1089–1096.
4.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, American Psychiatric Association, 2000.
5.
Giovannoni G, O’Sullivan JD, Turner K, Manson AJ, Lees AJL: Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies. J Neurol Neurosurg Psychiatry 2000;68:423–428.
6.
Evans AH, Katzenschlager R, Paviour D, et al: Punding in Parkinson’s disease: its relation to the dopamine dysregulation syndrome. Mov Disord 2004;19:397–405.
7.
O’Sullivan SS, Djamshidian A, Evans AH, Loane CM, Lees AJ, Lawrence AD: Excessive hoarding in Parkinson’s disease. Mov Disord 2010;25:1026–1033.
8.
Driver-Dunckley E, Samanta J, Stacy M: Pathological gambling associated with dopamine agonist therapy in Parkinson’s disease. Neurology 2003;61:422–423.
9.
Weintraub D: Dopamine and impulse control disorders in Parkinson’s disease. Ann Neurol 2008;64(suppl):S93–S100.
10.
Nirenberg MJ, Waters C: Compulsive eating and weight gain related to dopamine agonist use. Mov Disord 2006;21:524–529.
11.
Weintraub D, Koester J, Potenza MN, et al: Impulse control disorders in Parkinson disease: a cross-sectional study of 3,090 patients. Arch Neurol 2010;67:589–595.
12.
Lee J-Y, Kim J-M, Kim JW, et al: Association between the dose of dopaminergic medication and the behavioral disturbances in Parkinson disease. Parkinsonism Relat Disord 2010;16:202–207.
13.
Weintraub D, Sohr M, Potenza MN, et al: Amantadine use associated with impulse control disorders in Parkinson disease in cross-sectional study. Ann Neurol 2010;68:963–968.
14.
Miyasaki J, Hassan KL, Lang AE, Voon V: Punding prevalence in Parkinson’s disease. Mov Disord 2007;22:1179–1181.
15.
Antonini A, Siri C, Santangelo G, et al: Impulsivity and compulsivity in drug-naive patients with Parkinson’s disease. Mov Disord 2011;26:464–468.
16.
Giladi N, Weitzman N, Schreiber S, Shabtai H, Peretz C: 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 2007;21:501–506.
17.
Avanzi M, Baratti M, Cabrini S, Uber E, Brighetti G, Bonfà F: Prevalence of pathological gambling in patients with Parkinson’s disease. Mov Disord 2006;21:2068–2072.
18.
de Chazeron I, Llorca P-M, Chereau-Boudet I, et al: Hypersexuality and pathological gambling in Parkinson’s disease: a cross-sectional case-control study. Mov Disord 2011;26:2127–2730.
19.
Steeves TDL, Miyasaki J, Zurowski M, et al: Increased striatal dopamine release in parkinsonian patients with pathological gambling: a 11C raclopride PET study. Brain 2009;132:1376–1385.
20.
Ceravolo R, Frosini D, Rossi C, Bonuccelli U: Impulse control disorders in Parkinson’s disease: definition, epidemiology, risk factors, neurobiology and management. Parkinsonism Relat Disord 2009;155:S111–S115.
21.
Bjarkam CR, Sørensen JC: Therapeutic strategies for neurodegenerative disorders: emerging clues from Parkinson’s disease. Biol Psychiatry 2004;56:213–216.
22.
Levin BE, Katzen HL: Early cognitive changes and nondementing behavioral abnormalities in Parkinson’s disease; in Weiner WJ, Lang AE (eds): Behavioral Neurology of Movement Disorders. New York, Raven, 1995, pp 85–95.
23.
Green J, McDonald WM, Vitek JL, et al: Cognitive impairments in advanced PD without dementia. Neurology 2002;59:1320–1324.
24.
Dubois B, Pillon B: Cognitive deficits in Parkinson’s disease. J Neurol 1997;244:2–8.
25.
Brand M, Labudda K, Kalbe E, et al: Decision-making impairments in patients with Parkinson’s disease. Behav Neurol 2004;15:77–85.
26.
Bodi N, Keri S, Nagy H, et al: Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson’s patients. Brain 2009;132:2385–2395.
27.
Frank MJ, Seeberger LC, O’Reilly RC: By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science 2004;306:1940–1943.
28.
Frank MJ, Samanta J, Moustafa AA, Sherman SJ: Hold your horses: impulsivity, deep brain stimulation, and medication in parkinsonism. Science 2007;318:1309–1312.
29.
Milenkova M, Mohammadi B, Kollewe K, et al: Intertemporal choice in Parkinson’s disease. Mov Disord 2011;26:2004–2010.
30.
Gerlach M, Double K, Arzberger T, Leblhuber F, Tatschner T, Riederer P: Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum. J Neural Transm 2003;110:1119–1127.
31.
Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC: Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 1990;347:146–151.
32.
Cools R: Dopaminergic modulation of cognitive function – implications for L-DOPA treatment in Parkinson’s disease. Neurosci Biobehav Rev 2006;30:1–23.
33.
Cools R, Altamirano L, D’Esposito M: Reversal learning in Parkinson’s disease depends on medication status and outcome valence. Neuropsychologia 2006;44:1663–1673.
34.
Evans AH, Pavese N, Lawrence AD, et al: Compulsive drug use linked to sensitized ventral striatal dopamine transmission. Ann Neurol 2006;59:852–858.
35.
Santangelo G, Vitale C, Trojano L, Verde F, Grossi D, Barone P: Cognitive dysfunctions and pathological gambling in patients with Parkinson’s disease. Mov Disord 2009;24:899–905.
36.
Vitale C, Santangelo G, Trojano L, et al: Comparative neuropsychological profile of pathological gambling, hypersexuality, and compulsive eating in Parkinson’s disease. Mov Disord 2011;26:830–836.
37.
Djamshidian A, O’Sullivan SS, Lees A, Averbeck BB: Stroop test performance in impulsive and non impulsive patients with Parkinson’s disease. Parkinsonism Relat Disord 2011;17:212–214.
38.
Voon V, Thomsen T, Miyasaki JM, et al: Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease. Arch Neurol 2007;64:212–216.
39.
Voon V, Reynolds B, Brezing C, et al: Impulsive choice and response in dopamine agonist-related impulse control behaviors. Psychopharmacology (Berl) 2010;207:645–659.
40.
Voon V, Pessiglione M, Brezing C, et al: Mechanisms underlying dopamine-mediated reward bias in compulsive behaviors. Neuron 2010;65:135–142.
41.
Housden CR, O’Sullivan SS, Joyce EM, Lees AJ, Roiser JP: Intact reward learning but elevated delay discounting in Parkinson’s disease patients with impulsive-compulsive spectrum behaviors. Neuropsychopharmacology 2010;35:2155–2164.
42.
Rossi M, Gerschovich ER, de Achaval D, et al: Decision-making in Parkinson’s disease patients with and without pathological gambling. Eur J Neurol 2010;17:97–102.
43.
Claassen DO, van den Wildenberg WPM, Ridderinkhof KR, et al: The risky business of dopamine agonists in Parkinson’s disease and impulse control disorders. Behav Neurosci 2011;125:492–500.
44.
Djamshidian A, Jha A, O’Sullivan SS, et al: Risk and learning in impulsive and nonimpulsive patients with Parkinson’s disease. Mov Disord 2010;25:2203–2210.
45.
Djamshidian A, O’Sullivan SS, Wittmann BC, Lees AJ, Averbeck BB: Novelty seeking behaviour in Parkinson’s disease. Neuropsychologia 2011;49:2483–2488.
46.
Wu K, O’Sullivan S, Politis M, Bose S, Lees A, Piccini P: Rewarding visual cues increase dopamine neurotransmission in Parkinson’s patients with impulse control disorders: a PET study. J Neurol Neurosurg Psychiatry 2010;81:e29–e30.
47.
O’Sullivan SS, Wu K, Politis M, et al: Cue-induced striatal dopamine release in Parkinson’s disease-associated impulsive-compulsive behaviours. Brain 2011;134:969–978.
48.
Cilia R, Ko JH, Cho SS, et al: Reduced dopamine transporter density in the ventral striatum of patients with Parkinson’s disease and pathological gambling. Neurobiol Dis 2010;39:98–104.
49.
Cilia R, Siri C, Marotta G, et al: Functional abnormalities underlying pathological gambling in Parkinson disease. Arch Neurol 2008;65:1604–1611.
50.
Cilia R, Cho SS, Van Eimeren T, et al: Pathological gambling in patients with Parkinson’s disease is associated with fronto-striatal disconnection: a path modeling analysis. Mov Disord 2011;26:225–233.
51.
Van Eimeren T, Pellecchia G, Cilia R, et al: Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD. Neurology 2010;75:1711–1716.
52.
Rao H, Mamikonyan E, Detre JA, et al: Decreased ventral striatal activity with impulse control disorders in Parkinson’s disease. Mov Disord 2010;25:1660–1669.
53.
Frosini D, Pesaresi I, Cosottini M, et al: Parkinson’s disease and pathological gambling: results from a functional MRI study. Mov Disord 2010;25:2449–2453.
54.
Voon V, Gao J, Brezing Z, et al: Dopamine agonists and risk: impulse control disorders in Parkinson’s disease. Brain 2011;134:1438–1446.
55.
Rodriguez-Oroz MC, Lopez-Azcarate J, Garcia-Garcia D, et al: Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson’s disease. Brain 2011;134:36–49.
56.
Christenson GA, Faber RJ, deZwaan M: Compulsive buying: descriptive characteristics and psychiatric comorbidity. J Clin Psychiatry 1994;55:5–11.
57.
Weintraub D, Stewart S, Shea JA, et al: Validation of the Questionnaire for Impulsive-Compulsive Behaviors in Parkinson’s Disease (QUIP). Mov Disord 2009;24:1461–1467.
58.
Weintraub D, Mamikonyan E, Papay K, Shea JA, Xie SX, Siderowf A: Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale. Mov Disord 2012;27:242–247.
59.
Cabrini S, Baratti M, Bonfa F, Cabri G, Uber E, Avanzi M: Preliminary evaluation of the DDS-PC inventory: a new tool to assess impulsive-compulsive behaviours associated to dopamine replacement therapy in Parkinson’s disease. Neurol Sci 2009;30:307–313.
60.
Goetz CG, Tilley BC, Shaftman SR, et al: Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and climimetric testing results. Mov Disord 2008;23:2129–2170.
61.
Goetz CG, Tilley BC, Stebbins GT: Dopamine dysregulation syndrome item from the MDS-UPDRS. Mov Disord 2012;27:166.
62.
Mamikonyan E, Siderowf AD, Duda JE, et al: Long-term follow-up of impulse control disorders in Parkinson’s disease. Mov Disord 2008;23:75–80.
63.
Rabinak CA, Nirenberg MJ: Dopamine agonist withdrawal syndrome in Parkinson disease. Arch Neurol 2010;67:58–63.
64.
Broen M, Duits A, Visser-Vandewalle V, Temel Y, Winogrodzka A: Impulse control and related disorders in Parkinson’s disase patients treated with bilateral subthalamic nucleus stimulation: a review. Parkinsonism Relat Disord 2011;17:413–417.
65.
Thomas A, Bonnani L, Gambi F, Di Iorio A, Onofrj M: Pathological gambling in Parkinson disease is reduced by amantadine. Ann Neurol 2010;68:400–404.
66.
Walsh RA, Lang AE: Multiple impulse control disorders developing in Parkinson’s disease after initiation of amantadine. Mov Disord 2012;27:326.
67.
Lee J-Y, Lee EK, Park SS, et al: Association of DRD3 and GRIN2B with impulse control and related behaviors in Parkinsoon’s disease. Mov Disord 2009;24:1803–1810.
68.
Djamshidian A, O’Sullivan SS, Papadopoulos A, et al: Salivary cortisol levels in Parkinson’s disease and its correlation to risk behaviour. J Neurol Neurosurg Psychiatry 2011;82:1107-1111.
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2012
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