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Therapeutic effect of clozapine in psychotic decompensation in idiopathic Parkinson's disease

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Journal of Neural Transmission - Parkinson's Disease and Dementia Section

Summary

Seven patients with idiopathic Parkinson's disease, aged 62 to 76 years, average duration of the disease approximately eleven years, suffering from severe hallucinosis and paranoid delusions of different degree, in whom conventional therapeutic strategies (administration of benzodiazepines and mild neuroleptics) had no antipsychotic effect, received clozapine, a non-classical highly potent neuroleptic, while blood count was strictly monitored. Paranoid ideas disappeared in all seven patients after a maximum of four days administration of 25–125 mg/day. No deterioration of parkinsonian symptoms, quantified according to UPDRS was seen. Given the protection of clozapine, we could increase the L-dopa dose in two cases, thereby improving the patients' motor function. Blood count showed no abnormalities in any of the patients during an average observation period of seventeen months.

Our results support the assumption that clozapine has a potent antipsychotic effect in the treatment of psychotic decompensation in advanced Parkinson's disease in carefully selected patients. We saw no negative influence of the neurolpetic on extrapyramidal symptoms.

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References

  • Altar CA, Wasley AM, Neale RF, Stone GA (1986) Typical and atypical antipsychotic occupancy of D2 and S2 receptors: an autoradiographic analysis in rat brain. Brain Res Bull 16: 517–525

    Article  PubMed  Google Scholar 

  • Amsler HA, Teerehovi L, Barth E, Harjula K, Vuopio P (1977) Agranulocytosis in patients treated with clozapine. A study of the Finish epidemic. Acta Psychiatr Scand 56(4): 241–248

    PubMed  Google Scholar 

  • Anden N-E, Stock G (1973) Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J Pharm Pharmacol 25: 346–348

    PubMed  Google Scholar 

  • Barbeau A (1969) L-Dopa therapy in Parkinson's disease, a critical review of nine years experience. Can Med Assoc J 101: 781–800

    Google Scholar 

  • Barbeau A (1975) Résultats à long terme de la lévodopa dans la maladie de Parkinson. Union Med Con 104: 32–38

    Google Scholar 

  • Birkmayer W (1966) Experimentelle Befunde und neue Aspekte bei extrapyramidalen Erkrankungen. Wien Z Nervenheilkunde 23: 128–139

    Google Scholar 

  • Birkmayer W, Neumayer E (1972) Die Behandlung der Dopa-Psychosen mit L-Tryptophan. Nervenarzt 43: 76–78

    PubMed  Google Scholar 

  • Birkmayer W, Riederer P (1985) Die Parkinson-Krankheit: Biochemie, Klinik, Therapie, 2. Aufl. Springer, Wien New York S190–196

    Google Scholar 

  • Birkmayer W, Linauer W, Mentasti M (1971) Traitment à la L-Dopa combinée avec un inhibiteur der la decarboxylase (Ro 4-4602). In: de Ajuriaguerra J, Gauthier G (eds) Monoamines, noyaux gris centraux et syndrome de Parkinson. Masson, Paris, pp 435–441

    Google Scholar 

  • Birkmayer W, Danielczyk W, Riederer P (1983) Symptoms and side effects in the course of Parkinson's disease. J Neural Transm [Suppl 19]: 185–199

    Google Scholar 

  • Bowers MB, Rozitis A (1974) Regional differences in homovanillic acid concentration after acute and chronic administration of antipsychotic drugs. J Pharm Pharmacol 26: 743–745

    PubMed  Google Scholar 

  • Bürki HR (1986) Binding of psychoactive drugs to rat brain amine receptors, measured ex vivo, and their effects on the metabolism of biogenic amines. Naunyn-Schmiedebergs Arch Pharmacol 332: 258–266

    Article  PubMed  Google Scholar 

  • Bürki HR, Eichenberger E, Sayers AC, White TG (1975) Clozapine and the dopamine hypothesis of schizophrenia, a critical appraisal. Pharmacopsychiatry 8: 115–121

    Google Scholar 

  • Carlsson A (1978) Antipsychotic drugs, neurotransmitters, and schizophrenia. Am J Psychiatry 135: 164–173

    Google Scholar 

  • Casey DE (1989) Clozapine: neuroleptic-induced EPS and tardive dyskinesia. Psychopharmacology 99: 47–53

    Article  Google Scholar 

  • Celesia GG, Barr AN (1970) Psychosis and other psychiatric manifestation of levodopa therapy. Arch Neurol 23: 193–200

    PubMed  Google Scholar 

  • Celesia GG, Wanamaker WM (1972) Psychiatric disturbances in Parkinson's disease. Dis Nerv Syst 33: 577–583

    PubMed  Google Scholar 

  • Claghorn J, Honigfeld G, Abuzzahab FS, Wang R, Steinbook R, et al (1987) The risks and benefits of clozapine versus chlorpromazine. J Clin Psychopharmacol 7: 377–384

    PubMed  Google Scholar 

  • Conley RR, Schulz SC, Baker RW, Collins JF, Bell JA (1988) Clozapine efficacy in schizophrenic nonresponders. Psychopharmacol Bull 24: 269–274

    PubMed  Google Scholar 

  • Damasio AR, Lobo-Antunes J, Macedo C (1981) Psychiatric aspects in parkinsonism treated with L-dopa. J Neurol Neurosurg Psychiatry 34: 502–507

    Google Scholar 

  • De Smet Y, Ruberg M, Serdaru M, Dubois B, Lhermitte F, Agid Y (1982) Confusion, dementia and anticholinergics in Parkinson's disease. J Neurol Neurosurg Psychiatry 45: 1161–1164

    PubMed  Google Scholar 

  • Eichenberger E (1984) Pharmacology of fluperlapine compared with clozapine. Arzneimittelforschung 34: 110–113

    PubMed  Google Scholar 

  • Ereshefsky L, Watanabe MD, Tran-Johnson TK (1989) Clozapine: an atypical antipsychotic agent. Clin Pharm 8: 691–709

    PubMed  Google Scholar 

  • Fahn S, Elton RL and Members of the UPDRS Development Committee (1987) Unified Parkinson's disease rating scale. In: Fahn S, Marsden CD, Calne D, Goldstein M (eds) Recent developments in Parkinson disease, vol II, MacMillan Healthcare Information, Florham Park NJ, pp 153–163

    Google Scholar 

  • Fischer PA, Baas H, Hefner R (1990) Treatment of parkinsonian tremor with clozapine. J Neural Transm [PD-Sect] 2: 233–238

    Google Scholar 

  • Friedman JH, Lannon MC (1989) Clozapine in treatment of psychosis in Parkinson's disease. Neurology 39: 1219–1221

    PubMed  Google Scholar 

  • Friedman JH, Max J, Switf R (1987) Idiopathic Parkinson's disease in chronic shizophrenic patient: long-term treatment with clozapine and L-Dopa. Clin Neuropharmacol 10: 470–475

    PubMed  Google Scholar 

  • Gehlen W, Müller J (1974) Zur Therapie der Dopa-Psychosen mit L-Tryptophan. Dtsch Med Wochenschr 99: 457–463

    Google Scholar 

  • Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17: 427–442

    PubMed  Google Scholar 

  • Idänpään-Heikkilä J, Alhava E, Olkinnora M, Palva IP (1977) Agranulocytosis during treatment with clozapine. Eur J Clin Pharmacol 11: 193–198

    Article  PubMed  Google Scholar 

  • Kahn NA (1990) Clozapine for psychosis in Parkinson's patients. Clin Adv Treat Psychiatr Disord 4: 12–16

    Google Scholar 

  • Kane J, Honigfeld G, Singer J, Meltzer H (1988) Clozapine for the treatment-resistant schizophrenic. Arch Gen Psychiatry 45: 789–796

    PubMed  Google Scholar 

  • Lane RF, Blaha CD, Rivet JM (1988) Selective inhibition of mesolimbic dopamine release following chronic administration of clozapine: involvement of alpha1-noradrenergic receptors demonstrated by in vivo voltammetry. Brain Res 460: 398–491

    Article  PubMed  Google Scholar 

  • Lesser RP, Fahn S, Snider SR, Cote LJ, Isgreen WP, Barrett RE (1979) Analysis of the clinical problems in parkinsonism and the complications of long-term levodopa therapy. Neurology 29: 1253–1260

    PubMed  Google Scholar 

  • Lieberman A, Kupersmith M, Neophytides A (1980) Bromocriptine in Parkinson's disease: report on 106 patients treated up to 5 years. In: Calne DB, Goldstein M, Lieberman A, Thorner M (eds) Ergot compounds and brain function: neuroendocrine and neuropsychiatric aspects. Raven Press, New York, pp 245–253

    Google Scholar 

  • Liebermann A, Goldstein M, Leibowitz M, Neophytides A, Kupersmith M, Pact V, Kleinberg D (1981) Treatment of advanced Parkinson disease with pergolide. Neurology 31: 675–682

    PubMed  Google Scholar 

  • Ludin HP (1988) Das Parkinsonsyndrom. In: Baumgartner G, Cohen R, Grüsser OJ, Helmchen H, Schmidt LR (Hrsg) Kohlhammer, Stuttgart Berlin Köln Mainz, S104

    Google Scholar 

  • Marsden CD, Parkes JD (1977) Success and problems of long-term levodopa therapy in Parkinson's disease. Lancet i: 345–349

    Article  Google Scholar 

  • Marsden CD, Fahn S (1981) Problems in Parkinson's disease. In: Marsden CD, Fahn S (eds) Movement disorders. Butterworth Scientific, London, pp 1–7

    Google Scholar 

  • Mindham RHS (1970) Psychiatric syndromes in parkinsonism. J Neurol Neurosurg Psychiatry 30: 188–191

    Google Scholar 

  • Mindham RHS (1974) Psychiatric aspects of Parkinson's disease. Br J Hosp Med II: 411–414

    Google Scholar 

  • Moskovitz C, More H, Klawans H (1978) Levodopa induced psychosis: a kindling phenomenon. Am J Psychiatry 135: 218–226

    Google Scholar 

  • Ostergaard K, Dupont E (1988) Clozapine treatment of drug induced psychotic symptoms in the late stages of Parkinson's disease. Acta Neurol Scand 78: 349–350

    PubMed  Google Scholar 

  • Pakkenberg H, Pakkenberg B (1986) Clozapine in the treatment of tremor. Acta Neurol Scand 73: 295–297

    PubMed  Google Scholar 

  • Pfeiffer RF, Kang J, Graber B, Hofman R, Wilson J (1990) Clozapine for psychosis in Parkinson's disease. Mov Disord 5: 239–242

    Article  PubMed  Google Scholar 

  • Povlsen UJ, Noring U, Fog R, Gerlach J (1985) Toerability 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

    PubMed  Google Scholar 

  • Roberts HE, Dean RC, Stoudemire A (1989) Clozapine treatment of psychosis in Parkinson's disease. J Neuropsychiatr Clin Neurosci 1: 190–192

    Google Scholar 

  • Schneider E, Fischer PA, Jacobi P, Grotz A (1984) Exogene Psychosen beim Parkinsonsyndrom. Häufigkeit und Entstehungsbedingungen. Fortschr Neurol Psychiatr 52: 207–214

    PubMed  Google Scholar 

  • Scholz E, Dichgans J (1985) Treatment of drug-induced exogenous psychosis in parkinsonism with clozapine and fluperlapine. Eur Arch Psychiatr Neurol Sci 235: 60–64

    Article  Google Scholar 

  • Serby M, Angrist B, Leberman A (1978) Mental disturbances during bromocriptine and lergotile treatment of Parkinson's disease. Am J Psychiatry 135: 1227–1229

    PubMed  Google Scholar 

  • Snyder S, Greenberg D, Yamamura HI (1974) Antischizophrenic drugs and brain cholinergic receptors. Affinity for muscarini sites predicts extrapyramidal effects. Arch Gen Psychiatry 31: 58–61

    PubMed  Google Scholar 

  • Stern Y, Mayeux R, Ilson J, Fahn S, Cote L (1984) Pergolide therapy for Parkinson's disease: neurobehavioural changes. Neurology 34: 201–204

    PubMed  Google Scholar 

  • Tanner CM, Vogel C, Goetz CG, Klawans HL (1983) Hallucinations in Parkinson's disease: a population study. Ann Neurol 14: 136

    Google Scholar 

  • Watling KJ, Beer MS, Stanton JA, Newberry NR (1990) Interaction of the atypical neuroleptic clozapine with 5-HT3 receptors in the cerebral cortex and superior cervical ganglion of the rat. Eur J Pharmacol 183: 465–472

    Article  Google Scholar 

  • Westerink BHC, Lejeune B, Korf J, Van Praag HM (1977) On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs. Eur J Pharmacol 42: 179–190

    Article  PubMed  Google Scholar 

  • Wolters ECh, Hurwitz TA, Peppard RF, Calne DB (1989) Clozapine: an antipsychotic agent in Parkinson's disease? Clin Neuropharmacol 12: 83–90

    PubMed  Google Scholar 

  • Wolters ECh, Hurwitz TA, Mak E, Teal P, Peppard FR, Remick R, Calne S, Calne DM (1990) Clozapine in the treatment of parkinsonian patients with dopaminomimetic psychosis. Neurology 40: 832–834

    PubMed  Google Scholar 

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Pinter, M.M., Helscher, R.J. Therapeutic effect of clozapine in psychotic decompensation in idiopathic Parkinson's disease. J Neural Transm Gen Sect 5, 135–146 (1993). https://doi.org/10.1007/BF02251204

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