, Volume 11, Issue 1, pp 78–91 | Cite as

Treatment of Cognitive, Psychiatric, and Affective Disorders Associated with Parkinson’s Disease

  • Barbara Connolly
  • Susan H. Fox


Neuropsychiatric symptoms are common in Parkinson’s disease (PD) and add significantly to the burden of disease. These symptoms are most commonly part of the disease spectrum owing to pathological changes within relevant brain regions. Neuropsychiatric problems include disorders of cognition, ranging from mild cognitive impairment to dementia, psychotic symptoms, including, most commonly, well-formed visual hallucinations and paranoid delusions, and mood disorders, such as depression and anxiety. The other common cause of neuropsychiatric problem is secondary to use of dopaminergic drugs. Some PD patients may develop behavioral disorders, including impulse control disorders (ICDs) and addictive symptoms. Psychosis can be due to a mixture of underlying pathology, with triggering or worsening of symptoms with changes to PD medications. Currently, management of these disorders primarily uses therapies developed for general psychiatry and cognitive neurology, rather than specifically for PD. However, significant adverse effects, such as worsening of the motor symptoms of PD, can limit use of some drug therapies. Identification of drug-induced symptoms, such as ICDs, enables withdrawal of the offending drug as the principal management strategy. Research is ongoing in an effort to develop more specific therapies for PD-related neuropsychiatric symptoms.


Parkinson’s disease mood psychosis dementia impulse control disorder 


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  1. 1.
    Broeders M, De Bie RM, Velseboer DC, Speelman JD, Muslimovic D, Schmand B. Evolution of mild cognitive impairment in Parkinson disease. Neurology 2013;81:346-352.PubMedGoogle Scholar
  2. 2.
    Marras C, Armstrong MJ, Meaney CA, et al. Measuring mild cognitive impairment in patients with Parkinson's disease. Mov Disord 2013;28:626-633.PubMedGoogle Scholar
  3. 3.
    Litvan I, Aarsland D, Adler CH, et al. MDS Task Force on mild cognitive impairment in Parkinson's disease: critical review of PD-MCI. Mov Disord 2011;26:1814-1824.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Litvan I, Goldman JG, Troster AI, et al. Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord 2012;27:349-356.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology 2005;65:1239-1245.PubMedGoogle Scholar
  6. 6.
    Janvin CC, Larsen JP, Aarsland D, Hugdahl K. Subtypes of mild cognitive impairment in Parkinson's disease: progression to dementia. Mov Disord 2006;21:1343-1349.PubMedGoogle Scholar
  7. 7.
    Williams-Gray CH, Evans JR, Goris A, et al. The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort. Brain 2009;132:2958-2969.PubMedGoogle Scholar
  8. 8.
    Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord 2007;22:1689-1707.PubMedGoogle Scholar
  9. 9.
    McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies - Third report of the DLB consortium. Neurology 2005;65:1863-1872.PubMedGoogle Scholar
  10. 10.
    McKeith I, Mintzer J, Aarsland D, et al. Dementia with Lewy bodies. Lancet Neurol 2004;3:19-28.PubMedGoogle Scholar
  11. 11.
    Leroi I, McDonald K, Pantula H, Harbishettar V. Cognitive impairment in Parkinson disease: impact on quality of life, disability, and caregiver burden. J Geriatr Psychiatry Neurol 2012;25:208-214.PubMedGoogle Scholar
  12. 12.
    Weintraub D, Burn DJ. Parkinson's disease: the quintessential neuropsychiatric disorder. Mov Disord 2011;26:1022-1031.PubMedCentralPubMedGoogle Scholar
  13. 13.
    Uc EY, McDermott MP, Marder KS, et al. Incidence of and risk factors for cognitive impairment in an early Parkinson disease clinical trial cohort. Neurology 2009;73:1469-1477.PubMedGoogle Scholar
  14. 14.
    Jellinger KA. Neurobiology of cognitive impairment in Parkinson's disease. Expert Rev Neurother 2012;12:1451-1466.PubMedGoogle Scholar
  15. 15.
    Linazasoro G, Lasa A, Van Blercom N. Efficacy and safety of donepezil in the treatment of executive dysfunction in Parkinson disease - A pilot study. Clin Neuropharmacol 2005;28:176-178.PubMedGoogle Scholar
  16. 16.
    Hanagasi HA, Gurvit H, Unsalan P, et al. The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: a randomized, double-blind, placebo-controlled, multicenter study. Mov Disord 2011;26:1851-1858.PubMedGoogle Scholar
  17. 17.
    Marsh L, Biglan K, Gerstenhaber M, Williams JR. Atomoxetine for the treatment of executive dysfunction in Parkinson's disease: a pilot open-label study. Mov Disord 2009;24:277-282.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Weintraub D, Mavandadi S, Mamikonyan E, et al. Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease. Neurology 2010;75:448-455.PubMedGoogle Scholar
  19. 19.
    Auriel E, Hausdorff JM, Herman T, Simon ES, Giladi N. Effects of methylphenidate on cognitive function and gait in patients with Parkinson's disease - A pilot study. Clin Neuropharmacol 2006;29:15-17.PubMedGoogle Scholar
  20. 20.
    Espay AJ, Dwivedi AK, Payne M, et al. Methylphenidate for gait impairment in Parkinson disease: a randomized clinical trial. Neurology 2011;76:1256-1262.PubMedGoogle Scholar
  21. 21.
    Moreau C, Delval A, Defebvre L, et al. Methylphenidate for gait hypokinesia and freezing in patients with Parkinson's disease undergoing subthalamic stimulation: a multicentre, parallel, randomised, placebo-controlled trial. Lancet Neurol 2012;11:589-596.PubMedGoogle Scholar
  22. 22.
    Weintraub D, Somogyi M, Meng X. Rivastigmine in Alzheimer's disease and Parkinson's disease dementia: an ADAS-cog factor analysis. Am J Alzheimers Dis Other Demen 2011;26:443-449.PubMedGoogle Scholar
  23. 23.
    Rolinski M, Fox C, Maidment I, McShane R. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease. Cochrane Database Syst Rev 2012;3:CD006504.PubMedGoogle Scholar
  24. 24.
    Emre M, Aarsland D, Albanese A, et al. Rivastigmine for dementia associated with Parkinson's disease. N Engl J Med 2004;351:2509-2518.PubMedGoogle Scholar
  25. 25.
    Wesnes KA, McKeith I, Edgar C, Emre M, Lane R. Benefits of rivastigmine on attention in dementia associated with Parkinson disease. Neurology 2005;65:1654-1656.PubMedGoogle Scholar
  26. 26.
    Schmitt FA, Farlow MR, Meng XY, Tekin S, Olin JT. Efficacy of rivastigmine on executive function in patients with Parkinson's disease dementia. CNS Neurosci Ther 2010;16:330-336.PubMedGoogle Scholar
  27. 27.
    Olin JT, Aarsland D, Meng XY. Rivastigmine in the treatment of dementia associated with Parkinson's disease: effects on activities of daily living. Dement Geriatr Cogn Disord 2010;29:510-515.PubMedGoogle Scholar
  28. 28.
    McKeith I, Del ST, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000;356:2031-2036.PubMedGoogle Scholar
  29. 29.
    Oertel W, Poewe W, Wolters E, et al. Effects of rivastigmine on tremor and other motor symptoms in patients with Parkinson's disease dementia – a retrospective analysis of a double-blind trial and an open- label extension. Drug Saf 2008;31:79-94.PubMedGoogle Scholar
  30. 30.
    Sadowsky CH, Farlow MR, Meng X, Olin JT. Safety and tolerability of rivastigmine transdermal patch compared with rivastigmine capsules in patients switched from donepezil: data from three clinical trials. Int J Clin Pract 2010;64:188-193.PubMedGoogle Scholar
  31. 31.
    Rowan E, McKeith IG, Saxby BK, et al. Effects of donepezil on central processing speed and attentional measures in Parkinson's disease with dementia and dementia with Lewy bodies. Dement Geriatr Cogn Disord 2007;23:161-167.PubMedGoogle Scholar
  32. 32.
    Muller T, Welnic J, Fuchs G, Baas H, Ebersbach G, Reichmann H. The DONPAD-study--treatment of dementia in patients with Parkinson's disease with donepezil. J Neural Transm Suppl 2006;27-30.Google Scholar
  33. 33.
    Ravina B, Putt M, Siderowf A, et al. Donepezil for dementia in Parkinson's disease: a randomised, double blind, placebo controlled, crossover study. J Neurol Neurosurg Psychiatry 2005;76:934-939.PubMedGoogle Scholar
  34. 34.
    Leroi I, Brandt J, Reich SG, et al. Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson's disease. Int J Geriatr Psychiatry 2004;19:1-8.PubMedGoogle Scholar
  35. 35.
    Aarsland D, Laake K, Larsen JP, Janvin C. Donepezil for cognitive impairment in Parkinson's disease: a randomised controlled study. J Neurol Neurosurg Psychiatry 2002;72:708-712.PubMedGoogle Scholar
  36. 36.
    Dubois B, Tolosa E, Katzenschlager R, et al. Donepezil in Parkinson's disease dementia: a randomized, double-blind efficacy and safety study. Mov Disord 2012;27:1230-1238.PubMedGoogle Scholar
  37. 37.
    Mori E, Ikeda M, Kosaka K. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial. Ann Neurol 2012;72:41-52.PubMedGoogle Scholar
  38. 38.
    Litvinenko I, Odinak MM, Mogilnaya VI, Emelin A. Efficacy and safety of galantamine (Reminyl) in the treatment of dementia in patients with Parkinson's disease (Open-label controlled trial). Z Nevrol Psikhiatrii Im Ss Ko 2007;107:25-33.Google Scholar
  39. 39.
    Aarsland D, Hutchinson M, Larsen JP. Cognitive, psychiatric and motor response to galantamine in Parkinson's disease with dementia. Int J Geriatr Psychiatry 2003;18:937-941.PubMedGoogle Scholar
  40. 40.
    Emre M, Tsolaki M, Bonuccelli U, et al. Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2010;9:969-977.PubMedGoogle Scholar
  41. 41.
    Aarsland D, Ballard C, Walker Z, et al. Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo- controlled, multicentre trial. Lancet Neurol 2009;8:613-618.PubMedGoogle Scholar
  42. 42.
    Leroi I, Overshott R, Byrne EJ, Daniel E, Burns A. Randomized controlled trial of memantine in dementia associated with Parkinson's disease. Mov Disord 2009;24:1217-1221PubMedGoogle Scholar
  43. 43.
    Naismith SL, Mowszowski L, Diamond K, Lewis SJ. Improving memory in Parkinson's disease: a healthy brain ageing cognitive training program. Mov Disord 2013;28:1097-1103.PubMedGoogle Scholar
  44. 44.
    Hindle JV, Petrelli A, Clare L, Kalbe E. Nonpharmacological enhancement of cognitive function in Parkinson's disease: a systematic review. Mov Disord 2013;28:1034-1049.PubMedGoogle Scholar
  45. 45.
    Doody RS, Stevens JC, Beck C, et al. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1154-1166.Google Scholar
  46. 46.
    Hely MA, Morris JGL, Reid WGJ, Trafficante R. Sydney multicenter study of Parkinson's disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord 2005;20:190-199.PubMedGoogle Scholar
  47. 47.
    Fenelon G, Soulas T, Zenasni F, Cleret de LL. The changing face of Parkinson's disease-associated psychosis: a cross-sectional study based on the new NINDS-NIMH criteria. Mov Disord 2010;25:763-766.Google Scholar
  48. 48.
    Friedman JH. Parkinson disease psychosis: update. Behav Neurol 2013;27:469-477.PubMedGoogle Scholar
  49. 49.
    Gomez-Esteban JC, Tijero B, Somme J, et al. Impact of psychiatric symptoms and sleep disorders on the quality of life of patients with Parkinson's disease. J Neurol 2011;258:494-499.PubMedGoogle Scholar
  50. 50.
    Aarsland D, Larsen JP, Tandberg E, Laake K. Predictors of nursing home placement in Parkinson's disease: a population-based, prospective study. J Am Geriatr Soc 2000;48:938-942.PubMedGoogle Scholar
  51. 51.
    Forsaa EB, Larsen JP, WentzelLarsen T, et al. A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol 2010;67:996-1001.PubMedGoogle Scholar
  52. 52.
    Aarsland D, Kurz MW. The epidemiology of dementia associated with Parkinson disease. J Neurol Sci 2010;289:18-22.PubMedGoogle Scholar
  53. 53.
    Chopra A, Tye SJ, Lee KH, et al. Underlying neurobiology and clinical correlates of mania status after subthalamic nucleus deep brain stimulation in Parkinson's disease: a review of the literature. J Neuropsychiatry Clin Neurosci 2012;24:102-110.PubMedCentralPubMedGoogle Scholar
  54. 54.
    Schilbach L, Weiss PH, Kuhn J, Timmermann L, Klosterkotter J, Huff W. Pharmacological treatment of deep brain stimulation-induced hypomania leads to clinical remission while preserving motor benefits. Neurocase 2012;18:152-159.PubMedGoogle Scholar
  55. 55.
    Allen P, Laroi F, McGuire PK, Aleman A. The hallucinating brain: a review of structural and functional neuroimaging studies of hallucinations. Neurosci Biobehav Rev 2008;32:175-191.PubMedGoogle Scholar
  56. 56.
    Harding AJ, Broe GA, Halliday GM. Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain 2002;125:391-403.PubMedGoogle Scholar
  57. 57.
    Kalaitzakis ME, Christian LM, Moran LB, Graeber MB, Pearce RKB, Gentleman SM. Dementia and visual hallucinations associated with limbic pathology in Parkinson's disease. Parkinsonism Relat Disord 2009;15:196-204.PubMedGoogle Scholar
  58. 58.
    Boecker H, CeballosBaumann AO, Volk D, Conrad B, Forstl H, Haussermann P. Metabolic alterations in patients with Parkinson disease and visual hallucinations. Arch Neurol 2007;64:984-988.PubMedGoogle Scholar
  59. 59.
    Meppelink AM, de Jong BM, Renken R, Leenders KL, Cornelissen FW, van Laar T. Impaired visual processing preceding image recognition in Parkinson's disease patients with visual hallucinations. Brain 2009;132:2980-2993.PubMedGoogle Scholar
  60. 60.
    Ballanger B, Strafella AP, van Eimeren T, et al. Serotonin 2A receptors and visual hallucinations in Parkinson disease. Arch Neurol 2010;67:416-421.PubMedGoogle Scholar
  61. 61.
    Goldman JG, Vaughan CL, Goetz CG. An update expert opinion on management and research strategies in Parkinson's disease psychosis. Expert Opin Pharmacother 2011;12:2009-2024.PubMedCentralPubMedGoogle Scholar
  62. 62.
    Ford B, Lynch T, Greene P. Risperidone in Parkinson's disease. Lancet 1994 ;344:681.PubMedGoogle Scholar
  63. 63.
    Factor SA, Molho ES, Friedman JH. Risperidone and Parkinson's disease. Mov Disord 2002;17:221-222.PubMedGoogle Scholar
  64. 64.
    Breier A, Sutton VK, Feldman PD, et al. Olanzapine in the treatment of dopamimetic-induced psychosis in patients with Parkinson's disease. Biol Psychiatry 2002;52:438-445.PubMedGoogle Scholar
  65. 65.
    Ondo WG, Levy JK, Vuong KD, Hunter C, Jankovic J. Olanzapine treatment for dopaminergic-induced hallucinations. Mov Disord 2002;17:1031-1035.PubMedGoogle Scholar
  66. 66.
    Pintor L, Valldeoriola F, Bailles E, Marti MJ, Muniz A, Tolosa E. Ziprasidone versus clozapine in the treatment of psychotic symptoms in Parkinson disease: a randomized open clinical trial. Clin Neuropharmacol 2012;35:61-66.PubMedGoogle Scholar
  67. 67.
    Schindehutte J, Trenkwalder C. Treatment of drug-induced psychosis in Parkinson's disease with ziprasidone can induce severe dose-dependent off- periods and pathological laughing. Clin Neurol Neurosurg 2007;109:188-191.PubMedGoogle Scholar
  68. 68.
    Friedman JH. Atypical antipsychotic drugs in the treatment of Parkinson's disease. J Pharm Pract 2011;24:534-540.PubMedGoogle Scholar
  69. 69.
    Friedman JH, Berman RM, Goetz CG, et al. Open-label flexible-dose pilot study to evaluate the safety and tolerability of aripiprazole in patients with psychosis associated with Parkinson's disease. Mov Disord 2006;21:2078-2081.PubMedGoogle Scholar
  70. 70.
    Factor SA, Friedman JH, Lannon MC, Oakes D, Bourgeois K, Parkinson SG. Clozapine for the treatment of drug-induced psychosis in Parkinson's disease: results of the 12 week open label extension in the PSYCLOPS trial. Mov Disord 2001;16:135-139.PubMedGoogle Scholar
  71. 71.
    Pollak P, Tison F, Rascol O, et al. Clozapine in drug induced psychosis in Parkinson's disease: a randomised, placebo controlled study with open follow up. J Neurol Neurosurg Psychiatry 2004;75:689-695.PubMedGoogle Scholar
  72. 72.
    Ondo WG, Tintner R, Voung KD, Lai D, Ringholz G. Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease. Mov Disord 2005;20:958-963.PubMedGoogle Scholar
  73. 73.
    Rabey JM, Prokhorov T, Miniovitz A, Dobronevsky E, Klein C. Effect of quetiapine a double-blind in psychotic Parkinson's disease patients: labeled study of 3 months' duration. Mov Disord 2007;22:313-318.PubMedGoogle Scholar
  74. 74.
    Fernandez HH, Okun MS, Rodriguez RL, et al. Quetiapine improves visual hallucinations in Parkinson disease but not through normalization of sleep architecture: results from a double-blind clinical-polysomnography study. Int J Neurosci 2009;119:2196-2205.PubMedGoogle Scholar
  75. 75.
    Morgante L, Epifanio A, Spina E, et al. Quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis. Clin Neuropharmacol 2004;27:153-156.PubMedGoogle Scholar
  76. 76.
    Merims D, Balas M, Peretz C, Shabtai H, Giladi N. Rater-blinded, prospective comparison: quetiapine versus clozapine for Parkinson's disease psychosis. Clin Neuropharmacol 2006;29:331-337.PubMedGoogle Scholar
  77. 77.
    Meltzer HY, Mills R, Revell S, et al. Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of parkinson's disease psychosis. Neuropsychopharmacology 2010;35:881-892.PubMedGoogle Scholar
  78. 78.
    Cummings J, Isaacson S, Mills R, et al. Antipsychotic efficacy and motor tolerability in a phase III placebo-controlled study of pimavanserin in patients with Parkinson's disease psychosis (ACP-103-020). Mov Disord 2013;28:S170.Google Scholar
  79. 79.
    Burn D, Emre M, McKeith I, et al. Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease. Mov Disord 2006;21:1899-1907.PubMedGoogle Scholar
  80. 80.
    Postuma RB, Aarsland D, Barone P, et al. Identifying prodromal Parkinson's disease: pre-motor disorders in Parkinson's disease. Mov Disord 2012;27:617-626.PubMedGoogle Scholar
  81. 81.
    Lim SY, Fox SH, Lang AE. Overview of the extranigral aspects of Parkinson disease. Arch Neurol 2009;66:167-172.PubMedGoogle Scholar
  82. 82.
    Factor SA, Molho ES. Emergency department presentations of patients with Parkinson's disease. Am J Emerg Med 2000;18:209-215.PubMedGoogle Scholar
  83. 83.
    Hughes TA, Ross HF, Mindham RH, Spokes EG. Mortality in Parkinson's disease and its association with dementia and depression. Acta Neurol Scand 2004;110:118-123.PubMedGoogle Scholar
  84. 84.
    Schrag A, Jahanshahi M, Quinn N. What contributes to quality of life in patients with Parkinson's disease? J Neurol Neurosurg Psychiatry 2000;69:308-312.PubMedGoogle Scholar
  85. 85.
    Hurt CS, Weinman J, Lee R, Brown RG. The relationship of depression and disease stage to patient perceptions of Parkinson's disease. J Health Psychol 2012;17:1076-1088.PubMedGoogle Scholar
  86. 86.
    Santangelo G, Vitale C, Trojano L, et al. Relationship between depression and cognitive dysfunctions in Parkinson's disease without dementia. J Neurol 2009;256:632-638.PubMedGoogle Scholar
  87. 87.
    Ravina B, Camicioli R, Como PG, et al. The impact of depressive symptoms in early Parkinson disease. Neurology 2007;69:342-347.PubMedCentralPubMedGoogle Scholar
  88. 88.
    Leiknes I, Tysnes OB, Aarsland D, Larsen JP. Caregiver distress associated with neuropsychiatric problems in patients with early Parkinson's disease: the Norwegian ParkWest study. Acta Neurol Scand 2010;122:418-424.PubMedGoogle Scholar
  89. 89.
    Seppi K, Weintraub D, Coelho M, et al. The movement disorder society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson's disease. Mov Disord 2011;26:S42-S80.PubMedGoogle Scholar
  90. 90.
    Tan LC. Mood disorders in Parkinson's disease. Parkinsonism Relat Disord 2012;18:S74-S76.PubMedGoogle Scholar
  91. 91.
    Reijnders JSAM, Ehrt U, Weber WEJ, Aarsland D, Leentjens AFG. A systematic review of prevalence studies of depression in Parkinson's disease. Mov Disord 2008;23:183-189.PubMedGoogle Scholar
  92. 92.
    Ehrt U, Bronnick K, Leentjens AF, Larsen JP, Aarsland D. Depressive symptom profile in Parkinson's disease: a comparison with depression in elderly patients without Parkinson's disease. Int J Geriatr Psychiatry 2006;21:252-258.PubMedGoogle Scholar
  93. 93.
    van der Hoek TC, Bus BA, Matui P, van der Marck MA, Esselink RA, Tendolkar I. Prevalence of depression in Parkinson's disease: effects of disease stage, motor subtype and gender. J Neurol Sci 2011;310:220-224.PubMedGoogle Scholar
  94. 94.
    Aarsland D, Pahlhagen S, Ballard CG, Ehrt U, Svenningsson P. Depression in Parkinson disease--epidemiology, mechanisms and management. Nat Rev Neurol 2012;8:35-47.Google Scholar
  95. 95.
    Storch A, Schneider CB, Wolz M, et al. Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications. Neurology 2013;80:800-809.PubMedGoogle Scholar
  96. 96.
    Rektorova I, Rektor I, Bares M, et al. Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study. Eur J Neurol 2003;10:399-406.PubMedGoogle Scholar
  97. 97.
    Barone P, Poewe W, Albrecht S, et al. Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double- blind, placebo-controlled trial. Lancet Neurol 2010;9:573-580.PubMedGoogle Scholar
  98. 98.
    Barone P, Scarzella L, Marconi R, et al. Pramipexole versus sertraline in the treatment of depression in Parkinson's disease: a national multicenter parallel-group randomized study. J Neurol 2006;253:601-607.PubMedGoogle Scholar
  99. 99.
    Leentjens AF. The role of dopamine agonists in the treatment of depression in patients with Parkinson's disease: a systematic review. Drugs 2011;71:273-286.PubMedGoogle Scholar
  100. 100.
    Ray CK, Martinez-Martin P, Antonini A, et al. Rotigotine and specific non-motor symptoms of Parkinson's disease: post hoc analysis of RECOVER. Parkinsonism Relat Disord 2013;19:660-665.Google Scholar
  101. 101.
    Rocha FL, Murad MG, Stumpf BP, Hara C, Fuzikawa C. Antidepressants for depression in Parkinson's disease: systematic review and meta-analysis. J Psychopharmacol 2013;27:417-423.PubMedGoogle Scholar
  102. 102.
    Akca A, Mehmet AK, Sutcugil L, et al. Comparison of sertraline and venlafaxine treatments for depression in Parkinson's disease. Noropsikiyatri Arsivi 2011;48:201-206.Google Scholar
  103. 103.
    Richard IH, McDermott MP, Kurlan R, et al. A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease. Neurology 2012;78:1229-1236.PubMedGoogle Scholar
  104. 104.
    Menza M, Dobkin RD, Marin H, et al. A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology 2009;72:886-892.PubMedGoogle Scholar
  105. 105.
    Wermuth L, Sorensen PS, Timm S, et al. Depression in idiopathic Parkinson's disease treated with citalopram: A placebo-controlled trial. XXX;1998:163-169.Google Scholar
  106. 106.
    Leentjens AF, Vreeling FW, Luijckx GJ, Verhey FR. SSRIs in the treatment of depression in Parkinson's disease. Int J Geriatr Psychiatry 2003;18:552-554.PubMedGoogle Scholar
  107. 107.
    Devos D, Dujardin K, Poirot I, et al. Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study. Mov Disord 2008;23:850-857.PubMedGoogle Scholar
  108. 108.
    Skapinakis P, Bakola E, Salanti G, Lewis G, Kyritsis AP, Mavreas V. Efficacy and acceptability of selective serotonin reuptake inhibitors for the treatment of depression in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials - art. no. 49. BMC Neurol 2010;10:49.PubMedCentralPubMedGoogle Scholar
  109. 109.
    Ghaemi SN. Monoamine oxidase inhibitors and tricyclic antidepressants. Mood disorders: a practical guide. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2008.Google Scholar
  110. 110.
    Weiser R, Hernandez-Rojas J, Flores J, et al. Efficacy, tolerability, and safety of mirtazapine in the treatment of major depressive disorder due to Parkinson's disease. Mov Disord 2004;19:S205.Google Scholar
  111. 111.
    Zaluska M, Dyduch A. Bupropion in the treatment of depression in Parkinson's disease. Int Psychogeriatr 2011;23:325-327.PubMedGoogle Scholar
  112. 112.
    Raskin S, Durst R. Bupropion as the treatment of choice in depression associated with Parkinson's disease and it's various treatments. Med Hypotheses 2010;75:544-546.PubMedGoogle Scholar
  113. 113.
    Lemke MR. Effect of reboxetine on depression in Parkinson's disease patients. J Clin Psychiatry 2002;63:300-304.PubMedGoogle Scholar
  114. 114.
    Richard IH, Kurlan R, Tanner C, et al. Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Neurology 1997;48:1070-1077.PubMedGoogle Scholar
  115. 115.
    Ondo WG, Shinawi L, Davidson A, Lai D. Memantine for non-motor features of Parkinson's disease: a double-blind placebo controlled exploratory pilot trial. Parkinsonism Relat Disord 2011;17:156-159.PubMedGoogle Scholar
  116. 116.
    Secker DL, Brown RG. Cognitive behavioural therapy (CBT) for carers of patients with Parkinson's disease: a preliminary randomised controlled trial. J Neurol Neurosurg Psychiatry 2005;76:491-497.PubMedGoogle Scholar
  117. 117.
    Dobkin RD, Menza M, Allen LA, et al. Cognitive-behavioral therapy for depression in Parkinson's disease: a randomized, controlled trial. Am J Psychiatry 2011;168:1066-1074.PubMedCentralPubMedGoogle Scholar
  118. 118.
    Dobkin RD, Menza M, Allen LA, et al. Telephone-based cognitive-behavioral therapy for depression in Parkinson disease. J Geriatr Psychiatry Neurol 2011;24:206-214.PubMedCentralPubMedGoogle Scholar
  119. 119.
    Holzer JC, Giakas WJ, Mazure CM, Price BH. Dysarthria during ECT given for Parkinson's disease and depression. Convuls Ther 1992;8:201-203.PubMedGoogle Scholar
  120. 120.
    Friedman J, Gordon N. Electroconvulsive therapy in Parkinson's disease: a report on five cases. Convuls Ther 1992;8:204-210.PubMedGoogle Scholar
  121. 121.
    Bailine S, Kremen N, Kohen I, et al. Bitemporal electroconvulsive therapy for depression in a Parkinson disease patient with a deep-brain stimulator. J Ect 2008;24:171-172.PubMedGoogle Scholar
  122. 122.
    Dissanayaka NNW, Sellbach A, Matheson S, et al. Anxiety disorders in Parkinson's disease: prevalence and risk factors. Mov Disord 2010;25:838-845.PubMedGoogle Scholar
  123. 123.
    Factor SA. Literature review: intermittent subcutaneous apomorphine therapy in Parkinson's disease. Neurology 2004;62:S12-S17.PubMedGoogle Scholar
  124. 124.
    Baldwin D, Woods R, Lawson R, Taylor D. Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis. BMJ 2011;342:d1199.PubMedGoogle Scholar
  125. 125.
    Santangelo G, Trojano L, Barone P, Errico D, Grossi D, Vitale C. Apathy in Parkinson's disease: diagnosis, neuropsychological correlates, pathophysiology and treatment. Behav Neurol 2013;27:501–513.PubMedGoogle Scholar
  126. 126.
    Butterfield LC, Cimino CR, Oelke LE, Hauser RA, Sanchez-Ramos J. The independent influence of apathy and depression on cognitive functioning in Parkinson's disease. Neuropsychology 2010;24:721-730.PubMedGoogle Scholar
  127. 127.
    Barone P, Antonini A, Colosimo C, et al. The Priamo study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Mov Disord 2009;24:1641-1649.Google Scholar
  128. 128.
    Dujardin K, Sockeel P, Delliaux M, Destee A, Defebvre L. Apathy may herald cognitive decline and dementia in Parkinson's disease. Mov Disord 2009;24:2391-2397.PubMedGoogle Scholar
  129. 129.
    Harris E, McNamara P, Durso R. Apathy in patients with Parkinson disease as a function of side of onset. J Geriatr Psychiatry Neurol 2013;26:95-104.PubMedGoogle Scholar
  130. 130.
    Kirsch-Darrow L, Zahodne LB, Marsiske M, Okun MS, Foote KD, Bowers D. The trajectory of apathy after deep brain stimulation: from pre-surgery to 6 months post-surgery in Parkinson's disease. Parkinsonism Relat Disord 2011;17:182-188.PubMedCentralPubMedGoogle Scholar
  131. 131.
    Czernecki V, Pillon B, Houeto JL, Pochon JB, Levy R, Dubois B. Motivation, reward, and Parkinson's disease: influence of dopatherapy. Neuropsychologia 2002;40:2257-2267.PubMedGoogle Scholar
  132. 132.
    Czernecki V, Schupbach M, Yaici S, et al. Apathy following subthalamic stimulation in Parkinson disease: a dopamine responsive symptom. Mov Disord 2008;23:964-969.PubMedGoogle Scholar
  133. 133.
    Evans AH, Strafella AP, Weintraub D, Stacy M. Impulsive and compulsive behaviors in Parkinson's disease. Mov Disord 2009;24:1561-1570.PubMedGoogle Scholar
  134. 134.
    Mestre TA, Strafella AP, Thomsen T, Voon V, Miyasaki J. Diagnosis and treatment of impulse control disorders in patients with movement disorders. Ther Adv Neurol Disord 2013;6:175-188.PubMedCentralPubMedGoogle Scholar
  135. 135.
    Weintraub D, Koester J, Potenza MN, et al. Impulse control disorders in Parkinson disease a cross- sectional study of 3090 patients. Arch Neurol 2010;67:589-595.PubMedGoogle Scholar
  136. 136.
    Perez-Lloret S, Rey MV, Fabre N, et al. Prevalence and pharmacological factors associated with impulse-control disorder symptoms in patients with Parkinson disease. Clin Neuropharmacol 2012;35:261-265.PubMedGoogle Scholar
  137. 137.
    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;15:S111-S115.PubMedGoogle Scholar
  138. 138.
    Weintraub D, Papay K, Siderowf A. Screening for impulse control symptoms in patients with de novo Parkinson disease: a case-control study. Neurology 2013;80:176-180.PubMedGoogle Scholar
  139. 139.
    Poletti M, Logi C, Lucetti C, et al. A single-center, cross-sectional prevalence study of impulse control disorders in Parkinson disease: association with dopaminergic drugs. J Clin Psychopharmacol 2013;33:691–694.PubMedGoogle Scholar
  140. 140.
    Rabinak CA, Nirenberg MJ. Dopamine Agonist withdrawal syndrome in Parkinson disease. Arch Neurol 2010;67:58-63.PubMedGoogle Scholar
  141. 141.
    Pondal M, Marras C, Miyasaki J, et al. Clinical features of dopamine agonist withdrawal syndrome in a movement disorders clinic. J Neurol Neurosurg Psychiatry 2013;84:130-135.PubMedGoogle Scholar
  142. 142.
    Thomas A, Bonanni L, Gambi F, Di IA, Onofrj M. Pathological gambling in Parkinson disease is reduced by amantadine. Ann Neurol 2010;68:400-404.PubMedGoogle Scholar
  143. 143.
    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.PubMedGoogle Scholar
  144. 144.
    Bermejo PE, RuizHuete C, Anciones B. Zonisamide in managing impulse control disorders in Parkinson's disease. J Neurol 2010;257:1682-1685.PubMedGoogle Scholar
  145. 145.
    Ivanco LS, Bohnen NI. Effects of donepezil on compulsive hypersexual behavior in Parkinson disease: a single case study. Am J Ther 2005;12:467-468.PubMedGoogle Scholar
  146. 146.
    Sevincok L, Akoglu A, Akyol A. Quetiapine in a case with Parkinson disease and pathological gambling. J Clin Psychopharmacol 2007;27:107-108.PubMedGoogle Scholar
  147. 147.
    Rotondo A, Bosco D, Plastino M, Consoli A, Bosco F. Clozapine for medication-related pathological gambling in Parkinson disease. Mov Disord 2010;25:1994-1995.PubMedGoogle Scholar
  148. 148.
    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;13:377-382.PubMedGoogle Scholar
  149. 149.
    Klos KJ, Bower JH, Josephs KA, Matsumoto JY, Ahlskog JE. Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson's disease and multiple system atrophy. Parkinsonism Relat Disord 2005;11:381-386.PubMedGoogle Scholar
  150. 150.
    Bermejo PE. Topiramate in managing impulse control disorders in Parkinson's disease. Parkinsonism Relat Disord 2008;14:448-449.PubMedGoogle Scholar
  151. 151.
    Bosco D, Plastino M, Colica C, et al. Opioid antagonist naltrexone for the treatment of pathological gambling in Parkinson disease. Clin Neuropharmacol 2012;35:118-120.PubMedGoogle Scholar
  152. 152.
    Bortolato M, Cannas A, Solla P, Bini V, Puligheddu M, Marrosu F. Finasteride attenuates pathological gambling in patients with Parkinson disease. J Clin Psychopharmacol 2012;32:424-425.PubMedGoogle Scholar
  153. 153.
    Haussermann P, Goecker D, Beier K, Schroeder S. Low-dose cyproterone acetate treatment of sexual acting out in men with dementia. Int Psychogeriatr 2003;15:181-186.PubMedGoogle Scholar
  154. 154.
    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.PubMedCentralPubMedGoogle Scholar
  155. 155.
    Kurlan R. Disabling repetitive behaviors in Parkinson's disease. Mov Disord 2004;19:433-437.PubMedGoogle Scholar
  156. 156.
    Gschwandtner U, Aston J, Renaud S, Fuhr P. Pathologic gambling in patients with Parkinson's disease. Clin Neuropharmacol 2001;24:170-172.PubMedGoogle Scholar
  157. 157.
    Seedat S, Kesler S, Niehaus DJ, Stein DJ. Pathological gambling behaviour: emergence secondary to treatment of Parkinson's disease with dopaminergic agents. Depress Anxiety 2000;11:185-186.PubMedGoogle Scholar
  158. 158.
    Weintraub D, Xie SX, Stern M, et al. Randomized, double-blind, placebo-controlled study of naltrexone for impulse control disorders in Parkinson's disease. Mov Disord 2013;28:S141.Google Scholar
  159. 159.
    O'Sullivan SS, Evans AH, Lees AJ. Dopamine dysregulation syndrome: an overview of its epidemiology, mechanisms and management. CNS Drugs 2009;23:157-170.PubMedGoogle Scholar
  160. 160.
    Evans AH, Lawrence AD, Potts J, Appel S, Lees AJ. Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson disease. Neurology 2005;65:1570-1574.PubMedGoogle Scholar
  161. 161.
    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.PubMedGoogle Scholar
  162. 162.
    Sriram A, Ward HE, Hassan A, et al. Valproate as a treatment for dopamine dysregulation syndrome (DDS) in Parkinson's disease. J Neurol 2013;260:521-527.PubMedGoogle Scholar
  163. 163.
    Lim SY, Evans AH, Miyasaki JM. Impulse control and related disorders in Parkinson's disease: review. Ann N Y Acad Sci 2008;1142:85-107.PubMedGoogle Scholar
  164. 164.
    Kashihara K, Imamura T. Amantadine may reverse punding in Parkinson's disease - observation in a patient. Mov Disord 2008;23:129-130.PubMedGoogle Scholar
  165. 165.
    Hardwick A, Ward H, Hassan A, Romrell J, Okun MS. Clozapine as a potential treatment for refractory impulsive, compulsive, and punding behaviors in Parkinson's disease. Neurocase 2013;19:587–591.PubMedGoogle Scholar
  166. 166.
    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.PubMedGoogle Scholar
  167. 167.
    Fasano A, Ricciardi L, Pettorruso M, Bentivoglio AR. Management of punding in Parkinson's disease: an open-label prospective study. J Neurol 2011;258:656-660.PubMedGoogle Scholar
  168. 168.
    Okai D, Askey-Jones S, Samuel M, et al. Trial of CBT for impulse control behaviors affecting Parkinson patients and their caregivers. Neurology 2013;80:792-799.PubMedGoogle Scholar
  169. 169.
    Ardouin C, Voon V, Worbe Y, et al. Pathological gambling in Parkinson's disease improves on chronic subthalamic nucleus stimulation. Mov Disord 2006;21:1941-1946.PubMedGoogle Scholar
  170. 170.
    Eusebio A, Witjas T, Cohen J, et al. Subthalamic nucleus stimulation and compulsive use of dopaminergic medication in Parkinson's disease. J Neurol Neurosurg Psychiatry 2013;84:868–874.PubMedGoogle Scholar
  171. 171.
    Smeding HMM, Goudriaan AE, Foncke EMJ, Schuurman PR, Speelman JD, Schmand B. Pathological gambling after bilateral subthalamic nucleus stimulation in Parkinson disease. J Neurol Neurosurg Psychiatry 2007;78:517-519.PubMedGoogle Scholar
  172. 172.
    Lim SY, O'Sullivan SS, Kotschet K, et al. Dopamine dysregulation syndrome, impulse control disorders and punding after deep brain stimulation surgery for Parkinson's disease. J Clin Neurosci 2009;16:1148-1152.PubMedGoogle Scholar
  173. 173.
    Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. The Parkinson Study Group. N Engl J Med 1999;340:757-763.Google Scholar
  174. 174.
    Clozapine in drug-induced psychosis in Parkinson’s disease. The French Clozapine Parkinson Study Group. Lancet 1999;53:2041-2042.Google Scholar
  175. 175.
    Avila A, Cardona X, Martin-Baranera M, Maho P, Sastre F, Bello J. Does nefazodone improve both depression and Parkinson’s disease? A pilot randomized trial. J Clin Psychopharmacol 2003;23:509-513.PubMedGoogle Scholar
  176. 176.
    Antonini A, Tesei S, Zecchinelli A, et al. Randomized study of sertraline and low-dose amitriptyline in patients with Parkinson’s disease and depression: effect on quality of life. Mov Disord 2006;21:1119-1122.PubMedGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2013

Authors and Affiliations

  1. 1.Hamilton Health SciencesMcMaster UniversityHamiltonCanada
  2. 2.Morton and Gloria Shulman Movement Disorder ClinicUniversity of Toronto, Toronto Western HospitalTorontoCanada

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