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A Risk-Benefit Assessment of Drugs Used in the Management of Parkinson’s Disease

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  • Risk-Benefit Assessment
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Summary

The introduction of levodopa therapy in the 1960s and subsequent advances in neuropharmacology have revolutionised the management of Parkinson’s disease — but at a cost. Adverse effects are common, and an erratic pattern of response may develop with long term therapy due to a poorly understood interaction between drug treatment and disease progression. Not all features of the disease respond to drugs, and certain aspects such as psychiatric symptoms and postural imbalance may indeed be exacerbated. Patients vary considerably in their tolerance of anti-Parkinsonian drugs. Individual assessment of each patient’s medical, psychiatric and functional problems is required, with ongoing review and dose titration as the disease progresses.

In recent years there has been increasing interest in whether it is possible to influence the progression of Parkinson’s disease. As a result, more complicated drug regimens are being advocated for use in newly diagnosed patients. Arguments for and against this approach, as opposed to traditional symptomatic treatment, are presented.

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References

  1. Quinn NP. Antiparkinsonian drugs today. Drugs 1984; 28: 236–62

    Article  PubMed  CAS  Google Scholar 

  2. Molloy DW, Brooymans M. Anticholinergic medication and cognitive function in the elderly. J Clin Exp Gerontol 1989; 10: 89–98

    Google Scholar 

  3. Gribbin B, Pickering TG, Sleight P, et al. Effect of age and high blood pressure on baroreflex sensitivity in man. Circ Res 1971; 29: 424–31

    Article  PubMed  CAS  Google Scholar 

  4. Ruberg M, Ploska A, Javoy-Agid F, et al. Muscarinic binding and choline transferase activity in parkinsonian subjects with reference to dementia. Brain Res 1982; 232: 129–39

    Article  PubMed  CAS  Google Scholar 

  5. Perry RH, Tomlinson BE, Candy JM, et al. Cortical cholinergic deficit in mentally impaired parkinsonian patients. Lancet 1983; 2: 789–90

    Article  PubMed  CAS  Google Scholar 

  6. Horrocks PM, Vicary DK, Rees JE, et al. Anticholinergic withdrawal and benzhexol treatment of Parkinson’s disease. J Neurol Neurosurg Psychiatry 1973; 36: 936–41

    Article  PubMed  CAS  Google Scholar 

  7. Schwab RS, England AC, Poskanzer DC, et al. Amantadine in the treatment of Parkinson’s disease. JAMA 1969; 208: 1168–70

    Article  PubMed  CAS  Google Scholar 

  8. Nastuk WL, Su P, Doubilet P. Anticholinergic and membrane activities of amantadine in neuromuscular transmission. Nature 1976; 264: 76–9

    Article  PubMed  CAS  Google Scholar 

  9. Gianutsos G, Chute S, Dunn JP. Pharmacological changes in dompaminergic systems induced by long-term administration of amantadine. Eur J Pharmacol 1985; 110: 357–61

    Article  PubMed  CAS  Google Scholar 

  10. Kornhuber J, Bormann J, Retz W, et al. Memantine displaces [3H] MK-801 at therapeutic concentrations in post mortem frontal cortex. Eur J Pharmacol 1989; 166: 589–90

    Article  PubMed  CAS  Google Scholar 

  11. Dallos V, Heathfield K, Stone P, et al. Use of amantadine in Parkinson’s disease: results of a double blind trial. BMJ 1970; 4: 24–6

    Article  PubMed  CAS  Google Scholar 

  12. Hunter KR, Stern GM, Laurence DR, et al. Amantadine in parkinsonism. Lancet 1970; 1: 1127–9

    Article  PubMed  CAS  Google Scholar 

  13. Wilson JA, Farqhar TL, Primrose WJ, et al. Long-term amantadine treatment: the danger of withdrawal. Scott Med J 1987; 32: 135

    PubMed  CAS  Google Scholar 

  14. Parkes JD. Adverse effects of antiparkinsonian drugs. Drugs 1981; 21: 341–53

    Article  PubMed  CAS  Google Scholar 

  15. Parkes JD, Ziskha NH, Marsden CD, et al. Amantadine dosage in the treatment of Parkinson’s disease. Lancet 1970; 1: 1130–3

    Article  PubMed  CAS  Google Scholar 

  16. Horadam VW, Sharpe JG, Smilack JD, et al. Pharmacokinetics of amantadine hydrochloride in subjects with normal and impaired renal function. Ann Intern Med 1981; 94: 450–4

    Google Scholar 

  17. Wilson TW, Rajput AH. Amantadine — diazide interaction. Can Med Assoc J 1983; 129: 974–5

    PubMed  CAS  Google Scholar 

  18. Pinder RM, Brogden RM, Sawyer PR, et al. Levodopa and decarboxalase inhibitors: a review of their clinical pharmacology and use in the treatment of parkinsonism. Drugs 1976; 11: 329–77

    Article  PubMed  CAS  Google Scholar 

  19. Diamond SG, Markham CH. Present mortality in Parkinson’s disease: the ratio of observed to expected deaths with a method to calculate expected deaths. J Neural Transm Park Dis Dement Sec 1976; 38: 259–69

    Article  CAS  Google Scholar 

  20. Parker WD, Boyson SJ, Parks JK. Abnormalities of the electron transport chain in idiopathic Parkinson’s disease. Ann Neurol 1989; 26: 719–23

    Article  PubMed  Google Scholar 

  21. Olanow CW. Oxidation reactions in Parkinson’s disease. Neurology 1990; 40Suppl. 3: 32–7

    PubMed  Google Scholar 

  22. Marsden CD. Parkinson’s disease. Lancet 1990; 335: 948–52

    Article  PubMed  CAS  Google Scholar 

  23. Mouradian MM, Heuser IJE, Baronti F, et al. Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson’s Disease. Ann Neurol 1990; 27: 18–23

    Article  PubMed  CAS  Google Scholar 

  24. Blin J, Bonnet AM, Agid Y. Does levodopa aggravate Parkinson’s disease? Neurology 1988; 38: 1410–6

    Article  PubMed  CAS  Google Scholar 

  25. Anonymous. Levodopa: best taken before or after food? Pharm J 1994; 252: 637

    Google Scholar 

  26. Celesia GG, Barr AN. Psychosis and other psychiatric manifestations of levodopa therapy. Arch Neurol 1970; 230: 193–200

    Article  Google Scholar 

  27. Jenkins RB, Groh RH. Mental symptoms in parkinsonian patients treated with L-dopa. Lancet 1970; 2: 117–80

    Google Scholar 

  28. Sacks OW, Kohl MS, Messeloff CR, et al. Effects of levodopa in Parkinsonian patients with dementia. Neurology 1972; 22: 516–9

    Article  PubMed  CAS  Google Scholar 

  29. Moskovitz C, Moses H, Klawans HL. Levodopa induced psychosis: a kindling phenomenon. Am J Psychiatry 1978; 135: 669–75

    PubMed  CAS  Google Scholar 

  30. Anonymous. Sulpiride: an advance in neuroleptics? Drug Ther Bull 1984; 22: 31–3

    Google Scholar 

  31. Friedman JH, Lannon MC. Clozapine in the treatment of psychosis in Parkinson’s disease. Neurology 1989; 39: 1219–21

    Article  PubMed  CAS  Google Scholar 

  32. Faber R, Trimble MR. Electroconvulsive therapy in Parkinson’s disease and other movement disorders. Mov Disord 1991; 6: 293–303

    Article  PubMed  CAS  Google Scholar 

  33. Juncos JL, Fabbrini G, Mouradian MM, et al. Controlled release levodopa carbidopa (CR-5) in the management of Parkinsonian motor fluctuations. Arch Neurol 1987; 44: 1010–2

    Article  PubMed  CAS  Google Scholar 

  34. Askenasy JJM, Yahr MD. Reversal of sleep disturbance in PD by antiparkinsonian therapy: a preliminary study. Neurology 1985; 35: 527–32

    Article  PubMed  CAS  Google Scholar 

  35. Godwin-Austen RB, Frears CC, Bergman S. Incidence of side effects of levodopa during the introduction of treatment. BMJ 1971; 1: 267–8

    Article  PubMed  CAS  Google Scholar 

  36. Robertson DRC, Wood ND, Everest H, et al. The effect of age on the pharmcoconetics of levodopa administered alone and in the presence of carbidopa. Br J Clin Pharmacol 1989; 28: 61–9

    Article  PubMed  CAS  Google Scholar 

  37. Marsden CD, Parkes JD. On/off effect in patients with Parkinson’s disease on chronic levodopa therapy. Lancet 1976; 1: 292–6

    Article  PubMed  CAS  Google Scholar 

  38. Eriksson T, Magnusson T, Carlsson A, et al. On/off phenomenon in Parkinson’s disease: its correlation to the concentration of L-dopa in plasma. J Neural Transm Park Dis Dement Sec 1984; 59: 229–40

    Article  CAS  Google Scholar 

  39. DeJong GL, Meerwalt JD, Schmidt PIM. Factors that influence the occurrence of response fluctuations in Parkinson’s disease. Ann Neurol 1987; 22: 4–7

    Article  CAS  Google Scholar 

  40. Granerus AK, Carlsson A, Svanborg A. The aging neurone: influence on symptomatology and the theraputic response in Parkinson’s syndrome. Adv Neurol 1979; 24: 327–34

    Google Scholar 

  41. Gibb WR, Leer AJ. A comparison of clinical and pathological features of young and old onset Parkinson’s disease. Neurology 1988; 38: 1402–6

    Article  PubMed  CAS  Google Scholar 

  42. Lees AJ. The on/off phenomemon. J Neurol Neurosurg Psychiatry 1989; Suppl.: 29–37

    Google Scholar 

  43. Quinn N, Marsden CD, Parkes JD. Complicated response fluctuations in Parkinson’s disease: response to intravenous infusions of levodopa. Lancet 1982; 2: 412–5

    Article  PubMed  CAS  Google Scholar 

  44. Presthus J, Hajba A. Deprenyl (selegiline) combined with levodopa and a decarboxylase inhibitor in the treatment of Parkinson’s disease. Acta Neurol Scand 1983; 95: 127–33

    Article  CAS  Google Scholar 

  45. Robertson DRC, George CF. Drug therapy for Parkinson’s disease in the elderly. Br Med Bull 1990; 46: 124–46

    PubMed  CAS  Google Scholar 

  46. Golbe I. Deprenyl as symptomatic therapy in Parkinson’s disease. Clin Neuropharmacol 1988; 11: 387–400

    Article  PubMed  CAS  Google Scholar 

  47. Adverse effects and long term problems of antiparkinsonian therapy. Adverse Drug React Bull 1990; 145: 544–7

    Google Scholar 

  48. Lieberman AN, Goldstein M. Bromocriptine in Parkinson’s disease. Pharmacol Rev 1985; 37: 217–27

    PubMed  CAS  Google Scholar 

  49. Langtry HD, Clissold SP. Pergolide: a review of its pharmacological properties and therapeutic potential in Parkinson’s disease. Drugs 1990; 39: 491–506

    Article  PubMed  CAS  Google Scholar 

  50. Goldstein M, Lieberman A, Lew JY. The interaction of pergolide with central dopaminergic receptors. Proc Natl Acad Sci USA 1980; 77: 3725–8

    Article  PubMed  CAS  Google Scholar 

  51. Rinne UK. Early combination of bromocriptine and levodopa in the treatment of Parkinson’s disease: a five year follow up. Neurology 1987; 37: 826–8

    Article  PubMed  CAS  Google Scholar 

  52. Calne DB, Plotkin C, Williams AC, et al. Long term treatment of Parkinsonism with bromocriptine. Lancet 1978; 1: 1735–8

    Google Scholar 

  53. Teychenne PF, Calne DB, Leigh PN, et al. Idiopathic Parkinsonism treated with bromocriptine. Lancet 1975; 2: 473–6

    Article  PubMed  CAS  Google Scholar 

  54. Wass JAH, Thorner MO, Besser EN. Digital vasospasm with bromocriptine. Lancet 1976; 1: 1135

    Article  PubMed  CAS  Google Scholar 

  55. Eisler T, Hall RP, Kalavar KAR, et al. Erythromelalgia-like eruption in parkinsonian patients treated with bromocriptine. Neurology 1981; 31: 1368–70

    Article  PubMed  CAS  Google Scholar 

  56. Rinne UK. Pleuropulmonary changes during long-term bromocriptine treatment for Parkinson’s disease. Lancet 1981; 1: 44

    Article  Google Scholar 

  57. DuPont E, Olivarius B de F, Strong MJ. Bromocriptine induced colaginosis-like symptomotology in Parkinson’s disease. Lancet 1982; 1: 850–1

    Article  PubMed  CAS  Google Scholar 

  58. Monk BE, Parkes JD, Du Vivier A. Erythromalgia following pergolide administration. Br J Dermatol 1984; 111: 97–9

    Article  PubMed  CAS  Google Scholar 

  59. Critchley P, Grandas-Perez F, Quinn N, et al. Continuous subcutaneous lysuride infusions in Parkinson’s disease. J Neural Transm Suppl 1988; 27: 55–60

    PubMed  CAS  Google Scholar 

  60. Langston JW, Ballard P, Tetrud JW, et al. Chronic parkinsonism in humans due to a product of meperidine-analogue synthesis. Science 1983; 219: 979–80

    Article  PubMed  CAS  Google Scholar 

  61. Heikkila RE, Manzino L, Cabbat FC, et al. Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1, 2, 5, 6,-tetrahydropyridine by monoamine oxidase inhibitors. Nature 1984; 311: 467–9

    Article  PubMed  CAS  Google Scholar 

  62. Birkmayer W, Birkmayer GD. Effect of (−) deprenyl in the long-term treatment of Parkinson’s disease: a 10 years experience. J Neural Transm Suppl 1986; 22: 219–25

    PubMed  CAS  Google Scholar 

  63. Tetrud JW, Langsdon JW. The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease. Science 1989; 245: 519–22

    Article  PubMed  CAS  Google Scholar 

  64. Parkinson’s Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1989; 321: 1364–71

    Article  Google Scholar 

  65. Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s Disease. N Eng J Med 1993; 328: 176–83

    Article  Google Scholar 

  66. Rinne UK. Early combination of bromocriptine and levodopa in the treatment of Parkinson’s disease: a five year follow up. Neurology 1987; 37: 826–8

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. St Martin’s Hospital, Bath & West Community (NHS) Trust, Midford Road, Bath, Avon, BA2 5RP, England

    Ibrahim Y. O. Bodagh &  Dorothy R. C. Robertson (Consultant Geriatrician)

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  1. Ibrahim Y. O. Bodagh
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  2. Dorothy R. C. Robertson
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Bodagh, I.Y.O., Robertson, D.R.C. A Risk-Benefit Assessment of Drugs Used in the Management of Parkinson’s Disease. Drug-Safety 11, 94–103 (1994). https://doi.org/10.2165/00002018-199411020-00004

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