Treatment of behavioural disturbances in Parkinson’s disease

  • F. Valldeoriola
  • F. A. Nobbe
  • E. Tolosa
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 51)


Behavioural disorders in Parkinson’s disease can grossly be subdivided in primary disturbances and those which are related to drug treatment.

Depression and anxiety are a common feature in parkinsonian patients. Both occur independently of drug treatment. In general, most current antide­pressive and anxiolytic drugs could be administered in Parkinson’s disease with the same precautions as in the normal population. However, in single case reports modern serotonin reuptake blockers in Parkinson’s disease have been accused to worsen parkinsonian motor condition. Combinations of serotonin reuptake inhibitors with MAO-inhibitors like selegiline should be used with caution.

In the case of cognitive decline firstly an underlying depression should be disclosed or if existent be treated. Depression seems to be the single most important factor associated with the severity of dementia and early antidepressant treatment seems to decrease cognitive decline in depressed parkinsonian patients. Anticholinergic medications should be discontinued since they may cause mental side effects.

Sleep disorders in Parkinson’s disease are mainly caused by nocturnal akinesia, which causes sleep fragmentation or altered dreaming and nightmares, which might be a side-effect of dopaminergic treatment. In the first case the administration of a controlled release preparation of levodopa at bedtime may be indicated. If the sleep disorder is considered to be due to dopaminergic medication, a reduction of long-term acting agents like modern dopamine agonists and controlled-release levodopa should be considered.

In severe psychotic states related to drug treatment antiparkinsonian therapy must be carefully analysed and, if possible, reduced. If motor condition worsens and/or psychiatric symptoms do not improve, initiation with “atypical” neuroleptics like clozapine is indicated. The pharmacological and clinical properties of new antipsychotic drugs that can be used in Parkinson’s disease are revised.


Neurol Neurosurg Psychiatry Neuroleptic Malignant Syndrome Behavioural Disturbance Parkinsonian Patient Levodopa Therapy 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albert ML, Feldman RG, Willis A (1974) The “subcortical dementia” of progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 37: 121–130.PubMedCrossRefGoogle Scholar
  2. Algeri S, De Luigi A, De Simoni MG, et al. (1988) Multiple and complex effects of buspirone on central dopaminergic system. Psychopharmacol Biochem Behav 29: 823–826.CrossRefGoogle Scholar
  3. Akai T, Yamaguchi M, Mizuta E, Kuno S (1993) Effects of terguride, a partial D2 agonist, on MPTP-lesioned parkinsonian cynomolgus monkeys. Ann Neurol 33: 507–511.PubMedCrossRefGoogle Scholar
  4. American Psychiatric Association, Committee of Nomenclature and Statistics (1987) Diagnostic and statistical manual of mental disorders, 3rd edn, rev. American Psychiatric Association, Washington DC.Google Scholar
  5. Anderson GD, Rebec GV (1988) Clozapine and haloperidol in the amygdaloid complex: differential effects on dopamine transmission with long-term treatment. Biol Psychiatry 23: 497–506.PubMedCrossRefGoogle Scholar
  6. Andrade R, Nicoli RA (1987) Novel anxyolitics discriminate between postsynaptic serotonin receptors mediating different physiological responses on single neurons of the rat hippocampus. Arch Pharmacol 336: 5–10.CrossRefGoogle Scholar
  7. Baldessarini RJ, Frankenburg FR (1991) Clozapine, a novel antipsychotic drug. N Engl J Med 324: 746–754.PubMedCrossRefGoogle Scholar
  8. Baldessarini RJ, Marsh ER, Kula NS (1992) Interactions of fluoxetine with metabolism of dopamine and serotonin in rat brain regions. Brain Res 579: 152–156.PubMedCrossRefGoogle Scholar
  9. Barbeau A (1969) L-dopa therapy in Parkinson’s disease: a critical review of nine years’ experience. J Can Med Assoc 101: 7791–800. Google Scholar
  10. Baxter LR, Schwartz JM, Phelps ME, et al. (1989) Reduction of prefrontal glucose metabolism common to three types of depression. Arch Gen Psychiatry 46: 243–250.PubMedCrossRefGoogle Scholar
  11. Beardsley JV, Puletti F (1971) Personality (MMPI) and cognitive (WAIS) changes after levodopa treatment: occurrence in patients with Parkinson’s disease. Arch Neurol 25: 145–150.PubMedCrossRefGoogle Scholar
  12. Beasley BL, Nutt JG, Davenport RW, Chase TN (1980) Treatment with tryptophan of levodopa associated psychiatric disturbances. Arch Neurol 37: 155–156.PubMedCrossRefGoogle Scholar
  13. Beck AT, Ward CH, Mandelson M, Mock M, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4: 561–571.PubMedCrossRefGoogle Scholar
  14. Biggins CA, Boyd JL, Harrop FM, Medeley P, Mindham RHS, Randall JI, Spokes EGS (1992) A controlled, longitudinal study of dementia in Parkinson’s disease. J Neurol Neurosurg Psychiatry 55: 566–571.PubMedCrossRefGoogle Scholar
  15. Borison RL (1995) Clinical efficacy of serotonin-dopamine antagonists relative to classic neuroleptics. J Clin Psychopharmacol 15 [Suppl 1]: 24–29.CrossRefGoogle Scholar
  16. Borison RL, Fields JZ, Diamond BL (1981) Site-specific blockade of dopamine receptors by neuroleptic agents in human brain. Neuropharmacol 20: 1321–1322.Google Scholar
  17. Borison RL, Rathiraja AP, Bruce I, et al. (1992) Risperidone: clinical safety and efficacy in schizophrenia. Psychopharmacol Bull 28: 213–218.PubMedGoogle Scholar
  18. Bouchard RH, Pourcher E, Vincent P (1989) Fluoxetine and extrapyramidal side-effects. Am J Psychiatry 46: 1352–1253.Google Scholar
  19. Bowen FP, Kamienny RS, Burns MM, Yahr MD (1975) Parkinsonism: effect of levodopa treatment on concept formation. Neurology 25: 701–704.PubMedCrossRefGoogle Scholar
  20. Brown R, Marsden CD (1986) Visuospatial function in Parkinson’s disease. Brain 109: 987–1002.PubMedCrossRefGoogle Scholar
  21. Brown R, Jahnshahi M (1995) Depression in Parkinson’s disease: a psychosocial viewpoint. In: Weiner WG, Lang AE (eds) Advances in neurology, vol 65. Behavioural neurology of movement disorders. Raven Press, New York, pp 61–84.Google Scholar
  22. Bürki HR, Eichenberger E, Sayers AC, White TG (1975) Clozapine and the dopamine hypothesis of schizophrenia, a critical appraisal. Pharmakopsychiatr Neuropsychopharmakol 8: 115–121.PubMedGoogle Scholar
  23. Caparros-Lefebvre D, Pécheux N, Petit V, Duhamel A, Petit H (1995) Which factors predict cognitive decline in Parkinson’s disease. J Neurol Neurosurg Psychiatry 58: 51–55.PubMedCrossRefGoogle Scholar
  24. Celesia GG, Wanamaker WM (1972) Psychiatric disturbances in Parkinson’s disease. Dis Nerv Syst 33: 577–583.PubMedGoogle Scholar
  25. Ceulemans DLS, Gelders YG, Hoppenbrouwers ML, Reyntjens AJ, Janssen PAJ (1985) Effects of serotonin antagonists on schizophrenia: a pilot study with setoperone. Psychopharmacol 85: 329–332.CrossRefGoogle Scholar
  26. Cheng AVT, Ferrier IN, Morris CM, et al. (1991) Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer’s and Parkinson’s diseases. J Neurol Sci 106: 50–55.PubMedCrossRefGoogle Scholar
  27. Chinaglia G, Landwehrmeyer B, Probst A, Palacios JM (1993) Serotoninergic terminal transporters are differentially affected in Parkinson’s disease and progressive supranuclear palsy: an autoradiographic study with (3H)citalopram. Neuroscience 54: 691–699.PubMedCrossRefGoogle Scholar
  28. Chouinard G, Jones B, Remington G, et al. (1993) Canadian multi-centre placebo controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol 13: 25–40.PubMedCrossRefGoogle Scholar
  29. Cianchetti C (1985) Dopamine agonists and sleep in man. In: Wauquier A, Gaillard JM, Monti JM, Radulovacki M (eds) Sleep: neurotransmitters and neuromodulators. Raven Press, New York, pp 121–134.Google Scholar
  30. Claus A, Bollen J, De Cuyper H, et al. (1992) Risperidone versus haloperidol in the treatment of chronic schizophrenic in-patients: a multi-centre, double-blind comparative study. Acta Psychiatr Scand 85: 295–305.PubMedCrossRefGoogle Scholar
  31. Cohen BM, Herschel M, Aoba A (1979) Neuroleptic antimuscarinic and antiadrenergic activity of chlorpromazine, thioridazine and their metabolites. Psychiatry Res 1:199–208.PubMedCrossRefGoogle Scholar
  32. Cohen S, Chiles J, McNaughton A (1990) Weight gain associated with clozapine. Am J Psychiatry 147: 503–504.PubMedGoogle Scholar
  33. Cooper JA, Sagar HJ (1993) Incidental and intentional recall in Parkinson’s disease: an account based on diminished attentional resources. J Clin Exp Neuropsychol 15: 713–731.PubMedCrossRefGoogle Scholar
  34. Cooper JA, Sagar HJ, Doherty SM, et al. (1992) Different effects of dopaminergic and anticholinergic therapy on memory performance in Parkinson’s disease. Brain 115: 1701–1725.PubMedCrossRefGoogle Scholar
  35. Cowen PJ (1993) Serotonin receptor subtypes in depression: evidence from studies in neuroendocrine regulation. Clin Neuropharmacol 16 [Suppl 3]: 6–18.Google Scholar
  36. D’Amato RJ, Zweig RM, Whitehouse PJ, et al. (1987) Aminergic systems in Alzheimer’s disease and Parkinson’s disease. Ann Neurol 22: 229–236.PubMedCrossRefGoogle Scholar
  37. De Vos RA, Jansen EN, Stam FC, Ravid R, Swab DF (1995) “Lewy body disease”: clinico-pathological correlations in 18 consecutive cases of Parkinson’s disease with and without dementia. Clin Neurol Neurosurg 97: 12–22.CrossRefGoogle Scholar
  38. Dogali M, Fazzini E, Kolodny E, et al. (1995) Stereotactic ventral pallidotomy for Parkinson’s disease. Neurology 45: 753–761.PubMedCrossRefGoogle Scholar
  39. Dogali M, Sterio D, Fazzini E, et al. (1996) Effects of posteroventral pallidotomy in Parkinson’s disease. In: Battistin L, Scarlato G, Caraceni T, Ruggieri S (eds) Advances in neurology, vol 69. Parkinson’s disease. Lippincot-Raven, Philadelphia, pp 585–590.Google Scholar
  40. Donelli EF, Chase TN (1972) Intellectual and memory function in parkinsonian and non-parkinsonian patients treated with 1-dopa. Dis Nerv Syst 34: 119–123.Google Scholar
  41. Dubois B, Danze F, Pilon B, et al. (1987) Cholinergic-dependent deficits in Parkinson’s disease. Ann Neurol 22: 26–30.PubMedCrossRefGoogle Scholar
  42. Duncombe ME, Bradshaw JL, Iansek R, Phillips JG (1994) Parkinsonian patients without dementia or depression do not suffer from bradyphrenia as indexed by performance in mental rotation tasks with and without advance information. Neuropsychologia 32: 1383–1396.PubMedCrossRefGoogle Scholar
  43. Eison AS, Eison MS, Torrente JR, Wright RN, Yocca FD (1990) Nefazodone: preclinical pharmacology of a new antidepressant. Psychopharmacol Bull 26: 311–315.PubMedGoogle Scholar
  44. Factor SA, Brown D (1992) Clozapine prevents recurrence of psychosis in Parkinson’s disease. Mov Disord 7: 125–131.PubMedCrossRefGoogle Scholar
  45. Factor SA, McAlarney T, Sánchez-Ramos JR, Weiner WJ (1990) Sleep disorders and sleep effect in Parkinson’s disease. Mov Disord 5: 280–285.PubMedCrossRefGoogle Scholar
  46. Factor SA, Brown D, Molho ES, Podskalny GD (1994) Clozapine: a 2-year open trial in Parkinson’s disease patients with psychosis. Neurology 44: 544–546PubMedCrossRefGoogle Scholar
  47. Factor SA, Molho ES, Podskalny GD, Brown D (1995) Parkinson’s disease: drug-induced psychiatric states. In: Weiner WJ, Lang AE (eds) Advances in neurology, vol 65. Raven Press, New York, pp 115–138.Google Scholar
  48. Fahn S, Libsch LR, Cutler RW (1971) Monoamines in the human neostriatum: topographic distribution in normals and in Parkinson’s disease in their role in akinesia, rigidity, chorea and tremor. J Neurol Sci 14: 427–455.PubMedCrossRefGoogle Scholar
  49. Farde L, Nordström A-L (1992) PET analysis indicates typical central dopamine receptor occupancy in clozapine-treated patients. Br J Psychiatry 160 [Suppl 17]: 30–33.Google Scholar
  50. Farde L, Wiesel FA, Nordström A-L, Sedvall G (1989) Dl- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacol 99: 28–31.CrossRefGoogle Scholar
  51. Farina E, Cappa SF, Polimeni M, Magni E, Canesi M, Zechinelli A, Scarlato G, Mariani C (1994) Frontal dysfunction in early Parkinson’s disease. Acta Neurol Scand 90: 34–38.PubMedCrossRefGoogle Scholar
  52. Feighner JP, Pambakian R, Fowler RC, et al. (1989) A comparison of nefazodone imipramine and placebo in patients with severe to moderate depression. Psychopharmacol Bull 25: 219–221.PubMedGoogle Scholar
  53. Feighner JP, Boyer WF, Tyler DL, Neborsky RJ (1990) Adverse consequences of fluoxetine-MAOI combination therapy. J Clin Psychiatry 51: 222–225.PubMedGoogle Scholar
  54. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-Mental State”, a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198PubMedCrossRefGoogle Scholar
  55. Fontaine R (1993) Novel serotonergic mechanisms and clinical experience with nefazodone. Clin Neuropharmacol 16 [Suppl 3]: 45–50.Google Scholar
  56. Ford B, Lynch T, Greene P (1994) Risperidone in Parkinson’s disease. Lancet 344: 681.Google Scholar
  57. Fram D, Murphy D, Goodwin F, et al. (1970) L-Dopa and sleep in depressed patients. Psychophysiology 7: 316–317.Google Scholar
  58. Friedman JH (1991) The management of the levodopa psychoses. Clin Neuropharmacol 14: 283–295.PubMedCrossRefGoogle Scholar
  59. Friedman JH, Lannon MC (1989) Clozapine in the treatment of psychosis in Parkinson’s disease. Neurology 39: 1219–1221.PubMedCrossRefGoogle Scholar
  60. Fungfeld EW, Baggen M, Nedwidek P, et al. (1989) Double blind study with phosphatidylserine in parkinsonian patients with senile dementia of Alzheimer’s type (SDAT). Prog Clin Biol Res 317: 1235–1246.Google Scholar
  61. Gedye A (1991) Buspirone alone or with serotonergic diet reduced aggression in a developmentally disabled adult. Biol Psychiatry 30: 88–91.PubMedCrossRefGoogle Scholar
  62. Gerlach J, Peacock L (1994) Motor and mental side-effects of clozapine. J Clin Psychiatry. 55 S B: S107–S109.Google Scholar
  63. German DC, Menaye K, Smith WK, Woodward DJ, Saper CB (1989) Midbrain dopaminergic cell loss in Parkinson’s disease: computer visualization. Ann Neurol 26: 507–514.PubMedCrossRefGoogle Scholar
  64. Gerson SL (1993) Clozapine- deciphering the risks. N Engl J Med 329: 204–205.PubMedCrossRefGoogle Scholar
  65. Goetz CG, Stebbins GT (1993) Risk factors for nursing home placement in advanced. Parkinson’s disease. Neurology 43: 2227–2229.PubMedCrossRefGoogle Scholar
  66. Gómez Arévalo G, Gershanik OS (1993) Modulatory effect of clozapine on levodopa response in Parkinson’s disease: a preliminary study. Mov Disord 8: 349–354.CrossRefGoogle Scholar
  67. Goodwin FK (1971) Psychiatric side-effects of levodopa in man. JAMA 218: 1915–1920PubMedCrossRefGoogle Scholar
  68. Gotham AM, Brown RG, Marsden CD (1986) Depression in Parkinson’s disease: a quantitative and qualitative analysis. J Neurol Neurosurg Psychiatry 49: 381–389PubMedCrossRefGoogle Scholar
  69. Gross G, Xin X, Gastpar M (1991) Trimipramine: pharmacological reevaluation and comparison with clozapine. Neuropharmacol 30: 1159–1166.CrossRefGoogle Scholar
  70. Haring C, Neudorfer C, Schwitzer J, et al. (1994) EEG alterations in patients treated with clozapine in relation to plasma levels. Psychopharmacol 114: 97–100.CrossRefGoogle Scholar
  71. Halgin R, Riklin M, Misiak H (1977) Levodopa, parkinsonism, and recent memory. J Nerv Ment Dis 164: 268–272.PubMedCrossRefGoogle Scholar
  72. Halliday GM, Blumbergs PC, Cotton RGH, et al. (1990) Loss of brainstem serotonin- and substance P- containing neurons in Parkinson’s disease. Brain Res 510: 104–107.PubMedCrossRefGoogle Scholar
  73. Halperin JR, Murphy B (1992) Extrapyramidal reaction to ondansetron. Cancer 69: 1275PubMedCrossRefGoogle Scholar
  74. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56–62.PubMedCrossRefGoogle Scholar
  75. Harnel AR, Riklan M (1975) Cognitive and perceptual effects of long range 1-dopa therapy in parkinsonism. J Clin Psychol 31: 321–333.CrossRefGoogle Scholar
  76. Heinrich K, Klieser E, Lehmann E, Kinzier E (1991) Experimental comparison of the efficacy and compatibility of risperidone and clozapine in acute schizophrenia. In: Kane JM (ed) Risperidone: major progress in antipsychotic treatment. Oxford Clinical Communications, Oxford, pp 37–39.Google Scholar
  77. Hietanen M, Teräväinen H (1988) The effect of age of disease onset on neuropsychological performance in Parkinson’s disease. J Neurol Neurosurg Psychiatry 51: 244–249.PubMedCrossRefGoogle Scholar
  78. Huber SJ, Shulman HG, Paulson GW, Shuttleworth EC (1987) Fluctuations in plasma dopamine level impair memory in Parkinson’s disease. Neurology 37: 1371–1375.PubMedCrossRefGoogle Scholar
  79. Huber SJ, Shulman HG, Paulson GW, Shuttleworth EC (1989) Dose-dependent memory impairment in Parkinson’s disease. Neurology 39: 438–440.PubMedCrossRefGoogle Scholar
  80. Hughes AJ, Daniel SE, Kilford L, et al. (1992) Accuracy of diagnosis of idiopathic Parkinson’s disease: a clinicopathological study of 100 cases. J Neurol Neurosurg Psychiatry 55: 181–184.PubMedCrossRefGoogle Scholar
  81. Hurwitz TA, Calne DB, Waterman K (1988) Treatment of dopaminomimetic psychosis in Parkinson’s disease with electroconvulsive therapy. Can J Neurol Sci 15: 32–34PubMedGoogle Scholar
  82. Idänpään-Heikkilä J, Alhava E, Olkinuora M, Palva I (1975) Clozapine and agranulocytosis. Lancet ii: 611.CrossRefGoogle Scholar
  83. Ikeguchi K, Kuroda A (1995) Mianserin treatment of patients with psychosis induced by antiparkinsonian drugs. Eur Arch Psychiatry Clin Neurosci 244: 320–324.PubMedCrossRefGoogle Scholar
  84. Iversen LL (1993) The D4 and schizophrenia. Nature 365: 393.PubMedCrossRefGoogle Scholar
  85. Jankovic J, McDermott M, Carter J, et al. (1990) Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. Neurology 40: 1529–1534.PubMedCrossRefGoogle Scholar
  86. Jansen PAJ (1987) The development of new antipsychotic drugs: towards a new strategy in the management of chronic psychoses. J Drug Ther Res 12: 324–328.Google Scholar
  87. Jansen Steur ENH (1993) Increase of Parkinson disability after fluoxetine medication. Neurology 43: 211–213.CrossRefGoogle Scholar
  88. Jansen ENH (1994) Clozapine in the treatment of tremor in Parkinson’s disease. Acta Neurol Scand 89: 262–265.PubMedCrossRefGoogle Scholar
  89. Javoy-Agid F, Taquet H, Ploska A, et al. (1981) Distribution of catecholamines in the ventral mesencephalon of the human brain, with special reference to Parkinson’s disease. J Neurochem 36: 2101–2105.PubMedCrossRefGoogle Scholar
  90. Jiménez-Jiménez FJ, Tejeiro J, Martínez-Junquera G, et al. (1994) Parkinsonism exacerbated by paroxetine. Neurology 44: 2406.PubMedCrossRefGoogle Scholar
  91. Juul-Povlsen U, Noring U, Fog R, Gerlach J (1985) Tolerability and therapeutic effect of clozapine: a retrospective investigation of 216 patients, treated with clozapine for up to 12 years. Acta Psychiatr Scand 71: 176–185.PubMedCrossRefGoogle Scholar
  92. Kafi S, Gaillard J (1976) Brain dopamine receptors and sleep in the rat: effects of stimulation and blockade. Eur J Pharmacol 38: 357–363.PubMedCrossRefGoogle Scholar
  93. Karper LP, Salloway SP, Seibyl JP, Krystal JH (1992) Prolonged post-ictal encephalopathy in two patients with clozapine induced seizures. J Neuropsychiatry Clin Neurosci 4: 454–457.PubMedGoogle Scholar
  94. Kazee AM, Han LY (1995) Cortical Lewy bodies in Alzheimer’s disease. Arch Path Lab Med 119: 448–453.PubMedGoogle Scholar
  95. Kieburtz K, McDermott M, Como P, et al. (1994) The effect of deprenyl and tocopherol on cognitive performance in early untreated Parkinson’s disease. Neurology 44: 1756–1759.PubMedCrossRefGoogle Scholar
  96. Klawans HL (1988) Psychiatric side-effects during the treatment of Parkinson’s disease. J Neural Transm 27 [Suppl]: 117–122.Google Scholar
  97. Koller WC (1984) Disturbance of recent memory function in parkinsonian patients on anticholinergic therapy. Cortex 20: 307–311.PubMedGoogle Scholar
  98. Krupp P, Barnes P (1992) Clozapine-associated agranulocytosis: risk and aetiology. Br J. Psychiatry 160 [Suppl 17]: 38–40.Google Scholar
  99. Lang AE, Johnson K (1987) Akathisia in idiopathic Parkinson’s disease. Neurology 37: 477–481.PubMedCrossRefGoogle Scholar
  100. Lang AE, Sandor P, Duff J (1993) Remoxipride in Parkinson’s disease: differential response in patients with dyskinesias/fluctuations vs. psychosis. Ann Neurol 34: 301–302 (Abstract).Google Scholar
  101. Launer M (1992) Diarrhoea during treatment with clozapine. Br Med J 305: 1160.CrossRefGoogle Scholar
  102. Levin BE, Llabre MM, Reisman S (1991) A retrospective analysis of the effects of anticholinergic medication on memory performance in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 3: 412–416.PubMedGoogle Scholar
  103. Lew MF, Waters CH (1993) Clozapine treatment of parkinsonism with psychosis. J Am Geriatr Soc 41: 669–671.PubMedGoogle Scholar
  104. Lipinski JF Jr, Mallya G, Zimmerman, Pope HG Jr (1989) Fluoxetine-induced akathisia: clinical and theoretical implications. J Clin Psychiatry 50: 339–342.PubMedGoogle Scholar
  105. Lipper S (1976) Psychosis in patients on bromocriptine and levodopa with carbidopa. Lancet ii: 571–572.CrossRefGoogle Scholar
  106. Litvan I, Mohr E, Williams J, Fedio P, Chase TN (1991) Differential memory and executive functions in demented patients with Parkinson’s and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 54: 25–29.PubMedCrossRefGoogle Scholar
  107. Livingston MG (1994) Risperidone. Lancet 343: 457–460.PubMedCrossRefGoogle Scholar
  108. Lozano AM, Lang AE, Gálvez-Jiménez N, et al. (1995) Effect of GPi pallidotomy on motor function in Parkinson’s disease. Lancet 346: 1383–1387.PubMedCrossRefGoogle Scholar
  109. Marsden CD, Parkes JD, Quinn N (1982) Fluctuations of disability in Parkinson’s disease: clinical aspects. In: Marsden CD, Fahn S (eds) Movement disorders. Butterworth Scientific, London, pp 96–122.Google Scholar
  110. Martí MJ, Tolosa E (1991) Demencia en la enfermedad de Parkinson y en la enfermedad de Alzheimer: similitudes y diferencias. In: Esquerda JE, Gallego R, Gual A, Ramírez G, Rubia F (eds) Neurotransmisión y plasticidad sináptica. Espaxs, Barcelona, pp 293–309.Google Scholar
  111. Mayberg HS, Solomon DH (1995) Depression in Parkinson’s disease: a biochemical and organic viewpoint. In: Weiner WJ, Lang AE (eds) Advances in neurology, vol 65. Behavioral neurology of movement disorders. Raven Press, New York, pp 49–60.Google Scholar
  112. Mayberg HS, Starkstein SE, Sadzot B, et al. (1990) Selective hypometabolism in the inferior frontal lobe in depressed patients with Parkinson’s disease. Ann Neurol 28: 57–64.PubMedCrossRefGoogle Scholar
  113. Mayeux R, Stern Y, Rosen J, Leventhal J (1981) Depression, intellectual impairment, and Parkinson’s disease. Neurology 31: 645–650.PubMedCrossRefGoogle Scholar
  114. Mayeux R, Stern Y, Cote L, Williams JBW (1984) Altered serotonin metabolism in depressed patients in Parkinson’s disease. Am J Psychiatry 143: 756–759Google Scholar
  115. Mayeux R, Stern Y, Williams JBW, et al. (1986) Clinical and biochemical features of depression in Parkinson’s disease. Am J Psychiatry 143: 756–759.PubMedGoogle Scholar
  116. Mayeux R, Denaro J, Hemenegildo N, Marder K, Tang M-X, Cote LJ, Stern Y (1992) A population-based investigation of Parkinson’s disease with and without dementia. Arch Neurol 49: 492–497.PubMedCrossRefGoogle Scholar
  117. McCance-Katz EF, Marek KL, Price LH (1992) Serotonergic dysfunction in depression associated with Parkinson’s disease. Neurology 42: 1813–1814.PubMedCrossRefGoogle Scholar
  118. McDermott HP, Jankovic J, Parkinson Study Group (1992) Factors predictive of the need for levodopa therapy in early, untreated Parkinson’s disease. Neurology 42 [Suppl 3]: 441Google Scholar
  119. Meco G, Alessandria A, Binfati V, Giustini P (1994) Risperidone for hallucinations in levodopa-treated Parkinson’s disease patients. Lancet 343: 1370–1371.PubMedCrossRefGoogle Scholar
  120. Megens AAHP, Awouters FHL, Schotte A, et al. (1994) Survey on the pharmacodynamics of the new antipsychotic risperidone. Psychopharmacol 114: 9–23.CrossRefGoogle Scholar
  121. Meier MJ, Martin WE (1970) Intellectual changes associated with levodopa therapy. JAMA 213: 456–466.CrossRefGoogle Scholar
  122. Melamed E, Zoldan J, Friedberg G, Goldberg-Stein H (1993) Is hallucinosis in Parkinson’s disease due to central serotonergic hyperactivity? Mov Disord 8: 406–407.Google Scholar
  123. Meltzer HY (1993) New drugs for the treatment of schizophrenia. Psychiatr Clin North Am 16: 365–385.PubMedGoogle Scholar
  124. Meltzer HY, Koenig JL, Nash JF, Gudelsky GA (1989a) Melperone and clozapine: neuroendocrine effects of typical neuroleptic drugs. Acta Psychiatr Scand 352 [Suppl]: 24–29.CrossRefGoogle Scholar
  125. Meltzer HY, Matsubara S, LeeJ-C (1989b) Classification of typical and atypical antipsychotic drugs on the basis of dopamine Dl, D2 and serotonin-2 pKi values. J Pharmacol Exp Ther 251: 238–246.PubMedGoogle Scholar
  126. Meltzer HY, Kennedy J, Dai J, Parsa M, Riley D (1995) Plasma clozapine levels and the treatment of L-DOPA-induced psychosis in Parkinson’s disease. A high potency effect of clozapine. Neuropsychopharmacol 12: 39–45.Google Scholar
  127. Mendis T, Mohr E, George A, et al. (1994) Symptomatic relief from treatment-induced psychosis in Parkinson’s disease: an open-label pilot study with remoxipride. Mov Disord 9: 197–200.PubMedCrossRefGoogle Scholar
  128. Mindham RHS (1970) Psychiatric symptoms in parkinsonism. J Neurol Neurosurg Psychiatry 33:181–191.CrossRefGoogle Scholar
  129. Mohr E, Mendis T, Grimes DJ (1995) Late cognitive changes in Parkinson’s disease with emphasis on dementia. In: Weiner WJ, Lang AE (eds) Advances in neurology, vol 65. Behavioral neurology of movement disorders. Raven Press, New York, pp 97–113.Google Scholar
  130. Molinari SP, Kaminski R, Di Rocco A, Yahr MD (1995) The use of famotidine in the treatment of Parkinson’s disease: a pilot study. J Neural Transm [P-D Sect] 9: 243–247.CrossRefGoogle Scholar
  131. Montastruc JL, Fabre N, Blin O, et al. (1994) Does fluoxetine aggravate Parkinson’s disease? A pilot prospective trial. Mov Disord 9 [Suppl 1]: 99.Google Scholar
  132. Moore NA, Axton MS (1988) Production of climbing behaviour in mice requires both Dl and D2 receptor activation. Psychopharmacol 94: 263–266.Google Scholar
  133. Moore NA, Tye NC, Axton MS, Risius FC (1992) The behavioural pharmacology of olanzapine, a novel “atypical” antipsychotic agent. J Pharmacol Exp Ther 262: 545–551PubMedGoogle Scholar
  134. Moore S, Kenyon P (1994) Atypical antipsychotics, clozapine and sulpiride do not antagonise amphetamine-induced stereotyped locomotion. Psychopharmacol 114: 123–130.CrossRefGoogle Scholar
  135. Moskovitz C, Moses H, Klawans H(1978) Levodopa induced psychosis: a kindling phenomena. Am J Psychiatry 135: 6–10.Google Scholar
  136. Müller T, Becker T, Fritze J (1988) Neuroleptic malignant syndrome after clozapine plus carbamacepine. Lancet ii: 1500.CrossRefGoogle Scholar
  137. Naber D, Holzbach R, Perro C, Hippius H (1992) Clinical management of clozapine patients in relation to efficacy and side-effects. Br J Psychiatry 160 [Suppl 17]: 54–59Google Scholar
  138. Narabayashi H (1996) Does stereotactic treatment of Parkinson’s disease slow the progression of the disease? In: Battistin L, Scarlato G, Caraceni T, Ruggieri S (eds) Advances in neurology, vol 69. Parkinson’s disease. Lippincot-Raven, Philadelphia, pp 557–562.Google Scholar
  139. Nausieda PA (1992) Sleep in Parkinson’s disease. In: Koller WC (ed) Handbook of Parkinson’s disease. Marcel Dekker, New York, pp 451–467.Google Scholar
  140. Nausieda PA, Weiner WJ, Kaplan LR, Weber S, Klawans HL (1982) Sleep disruption in the course of chronic levodopa therapy: an early feature of the levodopa psychosis. Clin Neuropharmacol 5: 183–194.PubMedCrossRefGoogle Scholar
  141. Nausieda P, Tanner C, Klawans H (1983) Serotonergically active agents in the treatment of the levodopa induced psychosis. In: Fahn S, Calne DB, Shoulson I (eds) Advances in neurology, vol 37. Experimental therapeutics of movement disorders. Raven Press, New York, pp 23–32.Google Scholar
  142. Nausieda PA, Leo GJ, Chesney D (1994) Comparison of conventional and Sinemet CR on the sleep of parkinsonian patients. Neurology 44 [Suppl 2]: A219.Google Scholar
  143. Nutt JG, Gancher ST, Woodward WR (1988) Does inhibitory action of levodopa contribute to motor fluctuations? Neurology 38: 1553–1557.PubMedCrossRefGoogle Scholar
  144. Ostergaard K, Dupond E (1988) Clozapine treatment of drug-induced psychotic symptoms in late stages of Parkinson’s disease. Acta Neurol Scand 78: 349–350.PubMedCrossRefGoogle Scholar
  145. Palazzini E, Soliveri P, Filippini G, et al. (1995) Progression of motor and cognitive impairment in Parkinson’s disease. J Neurol 242: 535–540.PubMedCrossRefGoogle Scholar
  146. Parkinson J (1817) An essay on the shaking palsy. Whittingham and Rowland for Sherwood, Neely, and Jones, London.Google Scholar
  147. Parkinson Study Group (1993) Effect of deprenyl and tocopherol on the progression of disability in early Parkinson’s disease. N Engl J Med 328: 176–183.CrossRefGoogle Scholar
  148. Pfeiffer RF, Kang J, Graber B, Hofman R, Wilson J (1990) Clozapine for psychosis in Parkinson’s disease. Mov Disord 5: 239–242.PubMedCrossRefGoogle Scholar
  149. Pilowski LS, Costa DC, Elli PJ, et al. (1992) Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet 340: 199–202.CrossRefGoogle Scholar
  150. Pirozzolo FJ, Swihart AA, Rey GJ, Mahurin R, Jankovic J (1993) Cognitive impairments associated with Parkinson’s disease and other movement disorders. In: Jankovic J, Tolosa E (eds) Parkinson’s disease and movement disorders. Williams & Wilkins, Baltimore, pp 493–510.Google Scholar
  151. Pope HG Jr, Cole JO, Choras PT, Fulwiler CE (1986) Apparent neuroleptic malignant syndrome with clozapine and lithium. J Nerv Ment Dis 174: 493–495.PubMedCrossRefGoogle Scholar
  152. Rajput AH, Pahwa R, Pahwa P (1992) Mode of onset and prognosis in Parkinson’s disease. Neurology 42 [Suppl 3]: 419.Google Scholar
  153. Richelson E, Nelson A (1984) Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vivo. Eur J Pharmacol 103: 197–204.PubMedCrossRefGoogle Scholar
  154. Ring H, Bench CJ, Trimble MR, Brooks DJ, Frackowiak RS, Dolan RJ (1994) Depression in Parkinson’s disease. Br J Psychiatry 165: 333–339.PubMedCrossRefGoogle Scholar
  155. Rinne UK (1983) Problems associated with long term levodopa treatment of Parkinson’s disease. Acta Neurol Scand 95: 19–26.CrossRefGoogle Scholar
  156. Robinson RG (1988) Post-stroke depression and lesion location. Stroke 19: 125.Google Scholar
  157. Rubinstein M, Gershanik OS, Stefano FJE (1988) Different roles of Dl and D2 dopamine receptors involved in locomotor activity in supersensitive mice. Eur J Pharmacol 148: 419–426.PubMedCrossRefGoogle Scholar
  158. Rupniak NMJ, Hall MD, Mann S, et al. (1985) Chronic treatment of clozapine, unlike haloperidol, does not induce changes in D-2 receptor function in the rat. Biochem Pharmacol 34: 2755–2763.PubMedCrossRefGoogle Scholar
  159. Sadeh MS, Braham J, Modan M (1982) Effects of anticholinergic drugs on memory in Parkinson’s disease. Arch Neurol 39: 666–667.PubMedCrossRefGoogle Scholar
  160. Sano M, Stern Y, Marder K, Mayeux R (1990) A controlled trial of piracetam in intellectually impaired patients with Parkinson’s disease. Mov Disord 5: 230–234.PubMedCrossRefGoogle Scholar
  161. Santamaria J, Tolosa E (1992) Clinical subtypes of Parkinson’s disease and depression. In: Huber SG, Cummings JL (eds) Parkinson’s disease. Neurobehavioral aspects. Oxford University Press, New York, pp 217–228.Google Scholar
  162. Santamaria J, Tolosa E, Vallés A (1986) Parkinson’s disease with depression: a possible subgroup of idiopathic parkinsonism. Neurology 36: 1130–1133.PubMedCrossRefGoogle Scholar
  163. Scharf B, Moskowitz C, Moses H, Luptom M, Klawans H (1978) Dream phenomena induced by chronic levodopa therapy. J Neural Transm 43: 143–151.CrossRefGoogle Scholar
  164. Scholz E, Dichgans J (1985) Treatment of drug-induced exogenous psychosis in parkinsonism with clozapine and fluperlapine. Eur Arch Psychiatry 235: 60–64.CrossRefGoogle Scholar
  165. Seeman P (1992) Dopamine receptor sequences, therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4. Neuropsychopharmacol 7: 261–284.Google Scholar
  166. Seeman P, Guan HC, Van Tol HHM (1993) Dopamine D4 receptors elevated in schizophrenia. Nature 365: 441–445.PubMedCrossRefGoogle Scholar
  167. Shaikh S, Coller D, Kerwin RW, et al. (1993) Dopamine D4 receptor subtypes and response to clozapine. Lancet 341: 116.PubMedCrossRefGoogle Scholar
  168. Shaw KM, Lees AJ, Stern GM (1980) The impact of treatment with levodopa on Parkinson’s disease. Q J Med 49: 283–293.PubMedGoogle Scholar
  169. Sibley DR, Monsma FJ (1992) Molecular biology of dopamine receptors. TIPS 13: 61–69.PubMedGoogle Scholar
  170. Simpson GM, Cooper TA (1978) Clozapine plasma levels and convulsions. Am J Psychiatry 135: 99–100.PubMedGoogle Scholar
  171. Spencer DD, Robbins RJ, Naftolin F, et al. (1992) Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson’s disease. N Engl J Med 327: 1541–1548.PubMedCrossRefGoogle Scholar
  172. Starkstein SE, Preziosi TJ, Berthier ML, et al. (1989) Depression and cognitive impairment in Parkinson’s disease. Brain 112: 1141–1153.PubMedCrossRefGoogle Scholar
  173. Starkstein SE, Bolduc PL, Mayberg HS, Preziosi TJ, Robinson RG (1990) Cognitive impairment and depression in Parkinson’s disease: a follow-up study. J Neurol Neurosurg Psychiatry 53: 59–602.PubMedCrossRefGoogle Scholar
  174. Stern Y, Marder K, Tang MX, Mayeux R (1993) Antecedent clinical features associated with dementia in Parkinson’s disease. Neurology 50: 1192–1196.Google Scholar
  175. Stein MB, Heuser IJ, Juncos JL, Uhde TW (1990) Anxiety disorders in patients with Parkinson’s disease. Am J Psychiatry 147: 217–220.PubMedGoogle Scholar
  176. Tasker RR, DeCarvalho GC, Li CS, Kestle JRW (1996) Does thalamotomy alter the course of Parkinson’s disease? In: Battistin L, Scarlato G, Caraceni T, Ruggieri S (eds) Advances in neurology, vol 69. Parkinson’s disease. Lippincot-Raven, Philadelphia, pp 563–584.Google Scholar
  177. Thomas DR, Nelson DR, Johnson AM (1987) Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Psychopharmacology (Berlin) 93: 193–200.CrossRefGoogle Scholar
  178. Thomas P, Goudeman M (1992) Seizures with low doses of clozapine. Am J Psychiatry 149: 138–139.PubMedGoogle Scholar
  179. Tison F, Dartigues JF, Auriacombe S, Letenneur L, Boller F, Alpérovitcj A (1995) Dementia in Parkinson’s disease: a population-based study in ambulatory and instutionalized individuals. Neurology 45: 705–708.PubMedCrossRefGoogle Scholar
  180. Tolosa E, Valldeoriola F, Martí MJ (1994) New and emerging strategies for improving levodopa treatment. Neurology 44 [Suppl 6]: 35–44.Google Scholar
  181. Tröster AI, Paolo AM, Lyons KE, Glatt SL, Hubble JP, Koller WC (1995) The influence of depression on cognition in Parkinson’s disease: a pattern of impairment distinguishable from Alzheimer’s disease. Neurology 45: 672–676.PubMedCrossRefGoogle Scholar
  182. Van Beijsterveldt LEC, Geerts RJF, Leysen JE, et al. (1994) Regional brain distribution of risperidone and its active metabolite 9-hydroxy-risperidone in the rat. Psychopharmacol 114: 53–62.CrossRefGoogle Scholar
  183. Van Herwaarden G, Berger HJC, Horstink MWIM (1993) Short-term memory in Parkinson’s disease after withdrawel of long-term anticholinergic therapy. Clin Neuropharmacol 16: 438–443.PubMedCrossRefGoogle Scholar
  184. Van Tol HHM, Bunzow JR, Guan HC, et al. (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350: 610–619.PubMedCrossRefGoogle Scholar
  185. Walker JM, Matsumoto RR, Bowen WD, Gans DL, Jones KD, Walker FO (1988) Evidence for a role of haloperidol-sensitive sigma “opiate” receptors in the motor effects of antipsychotic drugs. Neurology 38: 961–965.PubMedCrossRefGoogle Scholar
  186. Waters CH (1994) Fluoxetine and selegiline: lack of significant interaction. Can J Neurol Sci 21: 259–261.PubMedGoogle Scholar
  187. White A, Corn TH, Feetham, Faulconbridge C (1991) Ondansetron in treatment of schizophrenia. Lancet 337: 1173.PubMedCrossRefGoogle Scholar
  188. Wiesel FA, Nordström AL, Farde L, Eriksson B (1994) An open clinical and biochemical study of ritanserin in acute patients with schizophrenia. Psychopharmacol 114: 31–38.CrossRefGoogle Scholar
  189. Wilson JA, Smith RG (1989) The prevalence and aetiology of long term L-dopa side-effects in elderly parkinsonian patients. Age Ageing 18: 11–16.PubMedCrossRefGoogle Scholar
  190. Wolters EC, Hurwitz TA, Mak E, et al. (1990) Clozapine in the treatment of parkinsonian patients with dopaminomimetic psychosis. Neurology 40: 832–834.PubMedCrossRefGoogle Scholar
  191. Yahr MD, Duvoisin RS, Schear MJ, Barrett RE, Hoehn MM (1969) Treatment of parkinsonism with levodopa. Arch Neurol 21: 343–354.PubMedCrossRefGoogle Scholar
  192. Yaryura-Tobias JA, Diamond B, Merlis S (1970) Psychiatric manifestations of levodopa. Dis Nerv Syst 31: 60–63.PubMedGoogle Scholar
  193. Zoldan J, Friedberg G, Goldberg-Stern, Melamed E (1993) Ondansentron for hallucinosis in advanced Parkinson’s disease. Lancet 341: 562–563.PubMedCrossRefGoogle Scholar
  194. Zoldan J, Friedberg G, Weizman A, Melamed E (1996) Ondansetron, a 5-HT3 antagonist for visual hallucinations and paranoid delusional disorder associated with chronic L-DOPA therapy in advanced Parkinson’s disease. In: Battistin L, Scarlato G, Caraceni T, Ruggieri S (eds) Advances in neurology, vol 69. Parkinson’s disease. Lippincott-Raven, Philadelphia, pp 541–544.Google Scholar

Copyright information

© Springer-Verlag/Wien 1997

Authors and Affiliations

  • F. Valldeoriola
    • 1
  • F. A. Nobbe
    • 1
  • E. Tolosa
    • 1
  1. 1.Parkinson’s Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic i Provincial de Barcelona, Institut Pi SunyerUniversity of BarcelonaSpain

Personalised recommendations