CNS Drugs

, Volume 22, Issue 7, pp 563–586 | Cite as

Impact of Newer Pharmacological Treatments on Quality of Life in Patients with Parkinson’s Disease

Review Article


Parkinson’s disease is a common progressive neurodegenerative condition with multiple motor and nonmotor features contributing to impairment of health-related quality of life (HR-QOL). Pharmacological treatments have been directed primarily at dopamine replacement with levodopa and agents to improve its bioavailability, including DOPA decarboxylase inhibitors, catechol-O-methyl-transferase (COMT) inhibitors and monoamine oxidase B (MAO-B) inhibitors, as well as synthetic dopamine agonists. These treatments to restore motor function are often very successful in early Parkinson’s disease, with objective improvement and concomitant improvement in subjective HR-QOL scores. However, as the disease progresses, motor complications and nonmotor symptoms predominate and are often refractory to therapeutic interventions. Antiparkinsonian medications have been shown to improve motor severity and motor complications of advancing disease, and there is increasing evidence that this can be translated into subjective improvement of HR-QOL from a patient’s point of view. However, the degree of improvement is less marked on HR-QOL scores than on motor scores, and some studies do not show improvement of HR-QOL in parallel to motor improvements. A number of explanations are possible, including limitations of the scales used, trial designs and lack of clinical improvement from the patients’ point of view. This review concentrates on clinical trials with an index of HR-QOL as an outcome measure, with particular emphasis on well designed, randomized, double-blind, placebo-controlled or active comparator-controlled methodology. Drugs that have been more recently added to the armamentarium of Parkinson’s disease, including the oral (pramipexole, ropinirole and piribedil) and transdermal (rotigotine) non-ergotamine-derived dopamine agonists, the novel MAO-B inhibitor rasagiline and the COMT inhibitors tolcapone and entacapone, were included. The effect of each of these agents on overall HR-QOL and depression, a factor that has been shown to significantly contribute to HR-QOL in several multivariate analyses, is discussed.

Overall, the literature search revealed 14 double-blind, placebo- or active comparator-controlled trials with an index of HR-QOL as an outcome measure. Entacapone resulted in HR-QOL improvement in nonfluctuating patients (one study) but not clearly in those with motor fluctuations (two studies). Tolcapone was only tested in patients with motor fluctuations and resulted in significant improvement in two of four studies using HR-QOL as an outcome measure. Rasagiline improved HR-QOL as monotherapy in early Parkinson’s disease (one study), but not clearly in more advanced disease (one study). Rotigotine improved HR-QOL in both early Parkinson’s disease (one study) and more advanced disease with motor fluctuations (one study). The impact of ropinirole and pramipexole on HR-QOL as monotherapy in early Parkinson’s disease versus placebo has not been assessed, but both agents have resulted in improved HR-QOL in patients with motor fluctuations (ropinirole one study, pramipexole one study). The evidence for antidepressant efficacy of antiparkinsonian medications is limited.


  1. 1.
    Bennett MC. The role of alpha-synuclein in neurodegenerative diseases. Pharmacol Ther 2005; 105: 311–31PubMedCrossRefGoogle Scholar
  2. 2.
    Schapira AH, Bezard E, Brotchie J, et al. Novel pharmacological targets for the treatment of Parkinson’s disease Nat Rev Drug Discov. 2006; 5: 845–54PubMedCrossRefGoogle Scholar
  3. 3.
    Braak H, Del Tredici JK, Bratzke H, et al. Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages). J Neurol 2002; 249Suppl. 3: III/1–5Google Scholar
  4. 4.
    Ponsen MM, Staffers D, Booij J, et al. Idiopathic hyposmia as a preclinical sign of Parkinson’s disease. Ann Neurol 2004; 56: 173–81PubMedCrossRefGoogle Scholar
  5. 5.
    Siegel JM. The stuff dreams are made of: anatomical substrates of REM sleep. Nat Neurosci 2006; 9: 721–2PubMedCrossRefGoogle Scholar
  6. 6.
    Braak H, Rub U, Del Tredici K. Cognitive decline correlates with neuropathological stage in Parkinson’s disease. J Neurol Sci 2006; 248: 255–8PubMedCrossRefGoogle Scholar
  7. 7.
    Williams-Gray CH, Foltynie T, Lewis SJ, et al. Cognitive deficits and psychosis in Parkinson’s disease: a review of pathophysiology and therapeutic options. CNS Drugs 2006; 20: 477–505PubMedCrossRefGoogle Scholar
  8. 8.
    Braak H, Bohl JR, Muller CM, et al. Stanley Fahn lecture 2005: the staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Mov Disord 2006; 21: 2042–51PubMedCrossRefGoogle Scholar
  9. 9.
    Wakabayashi K, Takahashi H. Neuropathology of autonomic nervous system in Parkinson’s disease. Eur Neurol 1997; 38Suppl. 2: 2–7PubMedCrossRefGoogle Scholar
  10. 10.
    Edwards LL, Quigley EM, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease: frequency and pathophysiology. Neurology 1992; 42: 726–32PubMedCrossRefGoogle Scholar
  11. 11.
    Fahn S, Elton RL, members of the UPDRS Development Committee. Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne BD, et al., editors. Recent developments in Parkinson’s disease. Florham Park (NJ): MacMillan Healthcare Information, 1987: 153–64Google Scholar
  12. 12.
    Holloway RG, Shoulson I, Fahn S, et al. Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol 2004; 61: 1044–53PubMedCrossRefGoogle Scholar
  13. 13.
    Whone AL, Watts RL, Stoessl AJ, et al. Slower progression of Parkinson’s disease with ropinirole versus levodopa: the REAL-PET study. Ann Neurol 2003; 54: 93–101PubMedCrossRefGoogle Scholar
  14. 14.
    Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord 2001; 16: 448–58PubMedCrossRefGoogle Scholar
  15. 15.
    Hauser RA, McDermott MP, Messing S. Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease. Arch Neurol 2006; 63: 1756–60PubMedCrossRefGoogle Scholar
  16. 16.
    Biglan KM, Holloway Jr RG, McDermott MP, et al. Risk factors for somnolence, edema, and hallucinations in early Parkinson disease. Parkinson Study Group CALM-PD Investigators. Neurology 2007; 69: 187–95Google Scholar
  17. 17.
    Avorn J, Schneeweiss S, Sudarsky LR, et al. Sudden uncontrollable somnolence and medication use in Parkinson disease. Arch Neurol 2005; 62: 1242–8PubMedCrossRefGoogle Scholar
  18. 18.
    Weintraub D, Siderowf AD, Potenza MN, et al. Association of dopamine agonist use with impulse control disorders in Parkinson disease. Arch Neurol 2006; 63: 969–73PubMedCrossRefGoogle Scholar
  19. 19.
    Zanettini R, Antonini A, Gatto G, et al. Valvular heart disease and the use of dopamine agonists for Parkinson’s disease. N Engl J Med 2007; 356: 39–46PubMedCrossRefGoogle Scholar
  20. 20.
    Nutt JG. Continuous dopaminergic stimulation: is it the answer to the motor complications of levodopa? Mov Disord 2007; 22: 1–9PubMedCrossRefGoogle Scholar
  21. 21.
    Raudino F. Nonmotor off in Parkinson’s disease. Acta Neurol Scand 2001; 104: 312–5PubMedCrossRefGoogle Scholar
  22. 22.
    Poewe W, Wolters E, Emre M, et al. Long-term benefits of rivastigmine in dementia associated with Parkinson’s disease: an active treatment extension study. EXPRESS Investigators. Mov Disord 2006; 21: 456–61CrossRefGoogle Scholar
  23. 23.
    Lang AE, Obeso JA. Challenges in Parkinson’s disease: restoration of the nigrostriatal dopamine system is not enough. Lancet Neurol 2004; 3: 309–16PubMedCrossRefGoogle Scholar
  24. 24.
    Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967; 17: 427–42PubMedCrossRefGoogle Scholar
  25. 25.
    Schwab RS, England Jr AC. Projection techniques for evaluating surgery in Parkinson’s disease. In: Gillingham FJ, Donaldson IML, editors. Third symposium on Parkinson’s disease, Royal College of Surgeons, 1968 May 20–22. Edinburgh: E&S Livingstone Ltd, 1969: 152–7Google Scholar
  26. 26.
    Wheatley K, Stowe RL, Clarke CE, et al. Evaluating drug treatments for Parkinson’s disease: how good are the trials? BMJ 2002; 324: 1508–11PubMedCrossRefGoogle Scholar
  27. 27.
    Parkinson Study Group. A randomized controlled trial comparing pramipexole with levodopa in early Parkinson’s disease: design and methods of the CALM-PD Study. Clin Neuro-pharmacol 2000; 23(1): 34–44Google Scholar
  28. 28.
    Goetz CG, Fahn S, Martinez-Martin P, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): process, format, and clinimetric testing plan. Mov Disord 2007; 22: 41–7PubMedCrossRefGoogle Scholar
  29. 29.
    Shulman LM, Taback RL, Rabinstein AA, et al. Non-recognition of depression and other non-motor symptoms in Parkinson’s disease. Parkinsonism Relat Disord 2002; 8: 193–7PubMedCrossRefGoogle Scholar
  30. 30.
    Chaudhuri KR, Martinez-Martin P, Brown RG, et al. The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: results from an international pilot study. Mov Disord 2007; 22: 1901–11PubMedCrossRefGoogle Scholar
  31. 31.
    Den Oudsten BL, Van Heck GL, De Vries J. Quality of life and related concepts in Parkinson’s disease: a systematic review. Mov Disord 2007; 22: 1528–37CrossRefGoogle Scholar
  32. 32.
    Schrag A. Quality of life and depression in Parkinson’s disease. J Neurol Sci 2006; 248: 151–7PubMedCrossRefGoogle Scholar
  33. 33.
    Peto V, Jenkinson C, Fitzpatrick R, et al. The development and validation of a short measure of functioning and well being for individuals with Parkinson’s disease. Qual Life Res 1995; 4: 241–8PubMedCrossRefGoogle Scholar
  34. 34.
    Jenkinson C, Fitzpatrick R. Cross-cultural evaluation of the short form 8-item Parkinson’s Disease Questionnaire (PDQ-8): results from America, Canada, Japan, Italy and Spain. Parkinsonism Relat Disord 2007; 13: 22–8PubMedCrossRefGoogle Scholar
  35. 35.
    Welsh M, McDermott MP, Holloway RG, et al. Development and testing of the Parkinson’s disease quality of life scale. Parkinson Study Group. Mov Disord 2003; 18: 637–45Google Scholar
  36. 36.
    Hobson P, Holden A, Meara J. Measuring the impact of Parkinson’s disease with the Parkinson’s disease quality of life questionnaire. Age Ageing 1999; 28: 341–6PubMedCrossRefGoogle Scholar
  37. 37.
    Hurst NP, Kind P, Ruta D, et al. Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D). Br J Rheumatol 1997; 36: 551–9PubMedCrossRefGoogle Scholar
  38. 38.
    Ware Jr JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992; 30: 473–83PubMedCrossRefGoogle Scholar
  39. 39.
    Gilson BS, Gilson JS, Bergner M, et al. The sickness impact profile: development of an outcome measure of health care. Am J Public Health 1975; 65: 1304–10PubMedCrossRefGoogle Scholar
  40. 40.
    Global Parkinson’s Disease Survey Steering Committee. Factors impacting on quality of life in Parkinson’s disease: results from an international survey. Mov Disord 2002; 17: 60–7CrossRefGoogle Scholar
  41. 41.
    Slawek J, Derejko M, Lass P. Factors affecting the quality of life of patients with idiopathic Parkinson’s disease: a cross-sectional study in an outpatient clinic attendees. Parkinsonism Relat Disord 2005; 11: 465–8PubMedCrossRefGoogle Scholar
  42. 42.
    Chapuis S, Ouchchane L, Metz O, et al. Impact of the motor complications of Parkinson’s disease on the quality of life. Mov Disord 2005; 20: 224–30PubMedCrossRefGoogle Scholar
  43. 43.
    Pechevis M, Clarke CE, Vieregge P, et al. Effects of dyskinesias in Parkinson’s disease on quality of life and health-related costs: a prospective European study. Trial Study Group. Eur J Neurol 2005; 12(12): 956–63PubMedCrossRefGoogle Scholar
  44. 44.
    Michalowska M, Fiszer U, Krygowska-Wajs A, et al. Falls in Parkinson’s disease: causes and impact on patients’ quality of life. Funct Neurol 2005; 20: 163–8PubMedGoogle Scholar
  45. 45.
    Moore O, Peretz C, Giladi N. Freezing of gait affects quality of life of peoples with Parkinson’s disease beyond its relationships with mobility and gait. Mov Disord 2007; 22: 2192–5PubMedCrossRefGoogle Scholar
  46. 46.
    Gomez-Esteban JC, Zarranz JJ, Lezcano E, et al. Influence of motor symptoms upon the quality of life of patients with Parkinson’s disease. Eur Neurol 2007; 57: 161–5PubMedCrossRefGoogle Scholar
  47. 47.
    Miller N, Noble E, Jones D, et al. Hard to swallow: dysphagia in Parkinson’s disease. Age Ageing 2006; 35: 614–8PubMedCrossRefGoogle Scholar
  48. 48.
    Weintraub D, Moberg PJ, Duda JE, et al. Effect of psychiatric and other non-motor symptoms on disability in Parkinson’s disease. J Am Geriatr Soc 2004; 52: 784–8PubMedCrossRefGoogle Scholar
  49. 49.
    Yoshii F, Takahashi H, Kumazawa R, et al. Parkinson’s disease and fatigue. J Neurol 2006 Dec; 253Suppl. 7: vii48–53PubMedCrossRefGoogle Scholar
  50. 50.
    Martinez-Martin P, Catalan MJ, Benito-Leon J, et al. Impact of fatigue in Parkinson’s disease: the Fatigue Impact Scale for Daily Use (D-FIS). Qual Life Res 2006; 15: 597–606PubMedCrossRefGoogle Scholar
  51. 51.
    Bronner G, Royter V, Korczyn AD, et al. Sexual dysfunction in Parkinson’s disease. J Sex Marital Ther 2004; 30: 95–105PubMedCrossRefGoogle Scholar
  52. 52.
    Moore O, Gurevich T, Korczyn AD, et al. Quality of sexual life in Parkinson’s disease. Parkinsonism Relat Disord 2002; 8: 243–6PubMedCrossRefGoogle Scholar
  53. 53.
    Swinn L, Schrag A, Viswanathan R, et al. Sweating dysfunction in Parkinson’s disease. Mov Disord 2003; 18: 1459–63PubMedCrossRefGoogle Scholar
  54. 54.
    Scaravilli T, Gasparoli E, Rinaldi F, et al. Health-related quality of life and sleep disorders in Parkinson’s disease. Neurol Sci 2003; 24: 209–10PubMedCrossRefGoogle Scholar
  55. 55.
    Sakakibara R, Shinotoh H, Uchiyama T, et al. Questionnaire-based assessment of pelvic organ dysfunction in Parkinson’s disease. Auton Neurosci 2001; 92: 76–85PubMedCrossRefGoogle Scholar
  56. 56.
    Kashihara K. Weight loss in Parkinson’s disease. J Neurol 2006; 253Suppl. 7: vii38–41PubMedCrossRefGoogle Scholar
  57. 57.
    Suzukamo Y, Ohbu S, Kondo T, et al. Psychological adjustment has a greater effect on health-related quality of life than on severity of disease in Parkinson’s disease. Mov Disord 2006; 21: 761–6PubMedCrossRefGoogle Scholar
  58. 58.
    Shimbo T, Goto M, Morimoto T, et al. Association between patient education and health-related quality of life in patients with Parkinson’s disease. Qual Life Res 2004; 13: 81–9PubMedCrossRefGoogle Scholar
  59. 59.
    Kuopio AM, Marttila RJ, Helenius H, et al. The quality of life in Parkinson’s disease. Mov Disord 2000; 15: 216–23PubMedCrossRefGoogle Scholar
  60. 60.
    Karlsen KH, Larsen JP, Tandberg E, et al. Influence of clinical and demographic variables on quality of life in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 1999; 66: 431–5PubMedCrossRefGoogle Scholar
  61. 61.
    Schrag A, Jahanshahi M, Quinn N. What contributes to quality of life in patients with Parkinson’s disease? J Neurol Neurosurg Psychiatry 2000; 69: 308–12PubMedCrossRefGoogle Scholar
  62. 62.
    Carod-Artal FJ, Vargas AP, Martinez-Martin P. Determinants of quality of life in Brazilian patients with Parkinson’s disease. Mov Disord 2007 July 30; 22(10): 1408–15PubMedCrossRefGoogle Scholar
  63. 63.
    Marras C, McDermott MP, Rochon PA, et al. Predictors of deterioration in health-related quality of life in Parkinson’s disease: results from the DATATOP trial. Parkinson Study Group DATATOP Investigators. Mov Disord 2008; 23: 653–9Google Scholar
  64. 64.
    Greene T, Camicioli R. Depressive symptoms and cognitive status affect health-related quality of life in older patients with Parkinson’s disease. J Am Geriatr Soc 2007; 55: 1888–90PubMedCrossRefGoogle Scholar
  65. 65.
    McKinlay A, Grace RC, Dalrymple-Alford JC, et al. A profile of neuropsychiatric problems and their relationship to quality of life for Parkinson’s disease patients without dementia. Parkinsonism Relat Disord 2008; 14: 37–42PubMedCrossRefGoogle Scholar
  66. 66.
    Beck AT, Steer RA, Ball R, et al. Comparison of Beck depression inventories-IA and -II in psychiatric outpatients. J Pers Assess 1996; 67: 588–97PubMedCrossRefGoogle Scholar
  67. 67.
    Roth M, Tym E, Mountjoy CQ, et al. CAMDEX: a standardised instrument for the diagnosis of mental disorder in the elderly, with special reference to the early detection of dementia. Br J Psychiatry 1986; 149: 698–709PubMedCrossRefGoogle Scholar
  68. 68.
    Fisk JD, Doble SE. Construction and validation of a fatigue impact scale for daily administration (D-FIS). Qual Life Res 2002; 11: 263–72PubMedCrossRefGoogle Scholar
  69. 69.
    Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1982–1983; 17(1): 37–49PubMedCrossRefGoogle Scholar
  70. 70.
    Sheikh JA, Yesavage JA. Geriatric depression scale (GDS): recent findings and development of a shorter version. In: Brink TL, editor. Clinical gerontology: a guide to assessment and intervention. New York. Howarth Press, 1986Google Scholar
  71. 71.
    Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983; 67(6): 361–70PubMedCrossRefGoogle Scholar
  72. 72.
    Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56–62PubMedCrossRefGoogle Scholar
  73. 73.
    Schrag A, Barone P, Brown RG, et al. Depression rating scales in Parkinson’s disease: critique and recommendations. Mov Disord 2007; 22: 1077–92PubMedCrossRefGoogle Scholar
  74. 74.
    Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–98PubMedCrossRefGoogle Scholar
  75. 75.
    Hunt SM, McKenna SP, McEwen J, et al. A quantitative approach to perceived health status: a validation study. J Epidemiol Community Health 1980; 34: 281–6PubMedCrossRefGoogle Scholar
  76. 76.
    Webster DD. Critical analysis of the disability in Parkinson’s disease. Mod Treat 1968; 5: 257–82PubMedGoogle Scholar
  77. 77.
    Zung WW. A self-rating depression scale. Arch Gen Psychiatry 1965; 12: 63–70PubMedCrossRefGoogle Scholar
  78. 78.
    Dewey II RB, Reimold SC, O’Suilleabhain PE. Cardiac valve regurgitation with pergolide compared with nonergot agonists in Parkinson disease. Arch Neurol 2007; 64: 377–80PubMedCrossRefGoogle Scholar
  79. 79.
    Martinez-Martin P, Deuschl G. Effect of medical and surgical interventions on health-related quality of life in Parkinson’s disease. Mov Disord 2007; 22(6): 757–65PubMedCrossRefGoogle Scholar
  80. 80.
    Hauser RA, Rascol O, Korczyn AD, et al. Ten-year follow-up of Parkinson’s disease patients randomized to initial therapy with ropinirole or levodopa. Mov Disord 2007; 22(16): 2409–17PubMedCrossRefGoogle Scholar
  81. 81.
    Grandas F, Hernandez B. Long-term effectiveness and quality of life improvement in entacapone-treated Parkinson’s disease patients: the effects of an early therapeutic intervention. The PRACTICOMT Study Group. Eur J Neurol 2007; 14: 282–9PubMedCrossRefGoogle Scholar
  82. 82.
    Reichmann H, Boas J, Macmahon D, et al. Efficacy of combining levodopa with entacapone on quality of life and activities of daily living in patients experiencing wearing-off type fluctuations. The ComQol Study Group. Acta Neurol Scand 2005; 111: 21–8PubMedCrossRefGoogle Scholar
  83. 83.
    Lyons KE, Pahwa R. Conversion from sustained release carbidopa/levodopa to carbidopa/levodopa/entacapone (Stalevo) in Parkinson disease patients. Clin Neuropharmacol 2006; 29: 73–6PubMedCrossRefGoogle Scholar
  84. 84.
    Antonini A, Mancini F, Canesi M, et al. Duodenal levodopa infusion improves quality of life in advanced Parkinson s disease. Neurodegener Dis 2008; 5(3–4): 244–6PubMedCrossRefGoogle Scholar
  85. 85.
    Deleu D, Northway MG, Hanssens Y. Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson’s disease. Clin Pharmacokinet 2002; 41: 261–309PubMedCrossRefGoogle Scholar
  86. 86.
    Nutt JG. Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Neurology 2000; 55(11 Suppl. 4): S33–7PubMedGoogle Scholar
  87. 87.
    Deane KH, Spieker S, Clarke CE. Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson’s disease. Cochrane Database Syst Rev 2004; (4): CD004554Google Scholar
  88. 88.
    Poewe WH, Deuschl G, Gordin A, et al. Efficacy and safety of entacapone in Parkinson’s disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria. Celomen Study Group. Acta Neurol Scand 2002; 105: 245–55CrossRefGoogle Scholar
  89. 89.
    Myllylä VV, Kultalahti ER, Haapaniemi H, et al. Twelve-month safety of entacapone in patients with Parkinson’s disease. The FILOMEN Study Group. Eur J Neurol 2001; 8: 53–60Google Scholar
  90. 90.
    Parkinson’s Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Ann Neurol 1997; 42: 747–55CrossRefGoogle Scholar
  91. 91.
    Rinne UK, Larsen JP, Siden A, et al. Entacapone enhances the response to levodopa in Parkinsonian patients with motor fluctuations. The Nomecomt Study Group. Neurology 1998; 51: 1309–14Google Scholar
  92. 92.
    Brooks DJ, Agid Y, Eggert K, et al. Treatment of end-of-dose wearing-off in Parkinson’s disease: stalevo (levodopa/ carbidopa/entacapone) and levodopa/DDCI given in combination with Comtess/Comtan (entacapone) provide equivalent improvements in symptom control superior to that of traditional levodopa/DDCI treatment. The TC-INIT Study Group. Eur Neurol 2005; 53: 197–202Google Scholar
  93. 93.
    Onofrj M, Thomas A, Vingerhoets F, et al. Combining entacapone with levodopa/DDCI improves clinical status and quality of life in Parkinson’s Disease (PD) patients experiencing wearing-off, regardless of the dosing frequency: results of a large multicentre open-label study. J Neural Transm 2004; 111: 1053–63PubMedCrossRefGoogle Scholar
  94. 94.
    Kupsch A, Trottenberg T, Bremen D. Levodopa therapy with entacapone in daily clinical practice: results of a post-marketing surveillance study. Curr Med Res Opin 2004; 20(1): 115–20PubMedCrossRefGoogle Scholar
  95. 95.
    Gershanik O, Emre M, Bernhard G, et al. Efficacy and safety of levodopa with entacapone in Parkinson’s disease patients suboptimally controlled with levodopa alone, in daily clinical practice: an international, multicentre, open-label study. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 963–71PubMedCrossRefGoogle Scholar
  96. 96.
    Durif F, Devaux I, Pere JJ, et al. Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson’s disease and end-of-dose deterioration in daily medical practice: an open, multicenter study. The F-01 Study Group. Eur Neurol 2001; 45: 111–8Google Scholar
  97. 97.
    Larsen JP, Worm-Petersen J, Siden A, et al. The tolerability and efficacy of entacapone over 3 years in patients with Parkinson’s disease. Eur J Neurol 2003; 10: 137–46PubMedCrossRefGoogle Scholar
  98. 98.
    Deuschl G, Vaitkus A, Fox GC, et al. Efficacy and tolerability of entacapone versus cabergoline in parkinsonian patients suffering from wearing-off. The CAMP Study Group. Mov Disord 2007; 22: 1550–5CrossRefGoogle Scholar
  99. 99.
    Koller W, Guarnieri M, Hubble J, et al. An open-label evaluation of the tolerability and safety of Stalevo (carbidopa, levodopa and entacapone) in Parkinson’s disease patients experiencing wearing-off. J Neural Transm 2005; 112: 221–30PubMedCrossRefGoogle Scholar
  100. 100.
    Fenelon G, Gimenez-Roldan S, Montastruc JL, et al. Efficacy and tolerability of entacapone in patients with Parkinson’s disease treated with levodopa plus a dopamine agonist and experiencing wearing-off motor fluctuations: a randomized, double-blind, multicentre study. J Neural Transm 2003; 110: 239–51PubMedCrossRefGoogle Scholar
  101. 101.
    Rascol O, Brooks D, Melamed E, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO [Lasting effect in Adjunct therapy with Rasagiline Given Once daily] study): a randomised, double-blind, parallel-group trial. Lancet 2005; 365: 947–54PubMedCrossRefGoogle Scholar
  102. 102.
    Olanow CW, Kieburtz K, Stern M, et al. Double-blind, placebo-controlled study of entacapone in levodopa-treated patients with stable Parkinson disease. The US01 Study Team. Arch Neurol 2004; 61: 1563–8CrossRefGoogle Scholar
  103. 103.
    Derogatis LR. The psychosocial adjustment to illness scale (PAIS). J Psychosom Res 1986; 30(1): 77–91PubMedCrossRefGoogle Scholar
  104. 104.
    Rajput AH, Martin W, Saint-Hilaire MH, et al. Tolcapone improves motor function in parkinsonian patients with the “wearing-off” phenomenon: a double-blind, placebo-controlled, multicenter trial. Neurology 1997; 49(4): 1066–71PubMedCrossRefGoogle Scholar
  105. 105.
    Baas H, Beiske AG, Ghika J, et al. Catechol-O-methyltransferase inhibition with tolcapone reduces the “wearing off” phenomenon and levodopa requirements in fluctuating parkinsonian patients. J Neurol Neurosurg Psychiatry 1997; 63: 421–8PubMedCrossRefGoogle Scholar
  106. 106.
    Adler CH, Singer C, O’Brien C, et al. Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa-carbidopa. Tolcapone Fluctuator Study Group III. Arch Neurol 1998; 55: 1089–95Google Scholar
  107. 107.
    Welsh MD, Dorflinger E, Chernik D, et al. Illness impact and adjustment to Parkinson’s disease: before and after treatment with tolcapone. Mov Disord 2000; 15: 497–502PubMedCrossRefGoogle Scholar
  108. 108.
    Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol 2005; 62: 241–8CrossRefGoogle Scholar
  109. 109.
    Biglan KM, Schwid S, Eberly S, et al. Rasagiline improves quality of life in patients with early Parkinson’s disease. The Parkinson Study Group. Mov Disord 2006; 21: 616–23Google Scholar
  110. 110.
    Jankovic J, Watts RL, Martin W, et al. Transdermal rotigotine: double-blind, placebo-controlled trial in Parkinson disease. Arch Neurol 2007; 64: 676–82PubMedCrossRefGoogle Scholar
  111. 111.
    Poewe WH, Rascol O, Quinn N, et al. Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson’s disease: a double-blind, double-dummy, randomised controlled trial. Lancet Neurol 2007; 6: 513–20PubMedCrossRefGoogle Scholar
  112. 112.
    Holloway RG, Shoulson I, Fahn S. Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol 2004; 61: 1044–53PubMedCrossRefGoogle Scholar
  113. 113.
    Parkinson Study Group. Pramipexole in levodopa-treated Parkinson disease patients of African, Asian, and Hispanic heritage. Clin Neuropharmacol 2007; 30: 72–85CrossRefGoogle Scholar
  114. 114.
    Pahwa R, Stacy MA, Factor SA, et al. Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease. EASE-PD Adjunct Study Investigators. Neurology 2007; 68: 1108–15Google Scholar
  115. 115.
    Myllyla V, Haapaniemi T, Kaakkola S, et al. Patient satisfaction with switching to Stalevo: an open-label evaluation in PD patients experiencing wearing-off (Simcom Study). Acta Neurol Scand 2006; 114: 181–6PubMedCrossRefGoogle Scholar
  116. 116.
    Korchounov A, Bogomazov G. Employment, medical absenteeism, and disability perception in Parkinson’s disease: a pilot double-blind, randomized, placebo-controlled study of entacapone adjunctive therapy. Mov Disord 2006; 21: 2220–4PubMedCrossRefGoogle Scholar
  117. 117.
    Naimark D, Krahn MD, Naglie G, et al. Primer on medical decision analysis: part 5. Working with Markov processes. Med Decis Making 1997; 17: 152–9PubMedCrossRefGoogle Scholar
  118. 118.
    Hudry J, Rinne JO, Keranen T, et al. Cost-utility model of rasagiline in the treatment of advanced Parkinson’s disease in Finland. Ann Pharmacother 2006; 40: 651–7PubMedCrossRefGoogle Scholar
  119. 119.
    Findley LJ, Lees A, Apajasalo M, et al. Cost-effectiveness of levodopa/carbidopa/entacapone (Stalevo) compared to standard care in UK Parkinson’s disease patients with wearing-off. Curr Med Res Opin 2005; 21: 1005–14PubMedCrossRefGoogle Scholar
  120. 120.
    Suchowersky O, Bailey P, Pourcher E, et al. Comparison of two dosages of tolcapone added to levodopa in nonfluctuating patients with PD. Clin Neuropharmacol 2001; 24: 214–20PubMedCrossRefGoogle Scholar
  121. 121.
    Olanow CW. Tolcapone and hepatotoxic effects. Tasmar Advisory Panel. Arch Neurol 2000; 57: 263–7Google Scholar
  122. 122.
    Lees AJ, Ratziu V, Tolosa E, et al. Safety and tolerability of adjunctive tolcapone therapy in early Parkinson’s disease patients. J Neurol Neurosurg Psychiatry 2007; 78(9): 944–8PubMedCrossRefGoogle Scholar
  123. 123.
    Koller W, Lees A, Doder M, et al. Randomized trial of tolcapone versus pergolide as add-on to levodopa therapy in Parkinson’s disease patients with motor fluctuations. Tolcapone/Pergolide Study Group. Mov Disord 2001; 16: 858–66CrossRefGoogle Scholar
  124. 124.
    Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol 2002; 59: 1937–43CrossRefGoogle Scholar
  125. 125.
    Siderowf A, Stern M. Clinical trials with rasagiline: evidence for short-term and long-term effects. Neurology 2006; 66(10 Suppl. 4): S80–8PubMedCrossRefGoogle Scholar
  126. 126.
    Nyholm D, Remahl AI, Dizdar N, et al. Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology 2005; 64: 216–23PubMedCrossRefGoogle Scholar
  127. 127.
    Antonini A, Isaias IU, Canesi M, et al. Duodenal levodopa infusion for advanced Parkinson’s disease: 12-month treatment outcome. Mov Disord 2007; 22(8): 1145–9PubMedCrossRefGoogle Scholar
  128. 128.
    Nilsson D, Nyholm D, Aquilonius SM. Duodenal levodopa infusion in Parkinson’s disease: long-term experience. Acta Neurol Scand 2001; 104(6): 343–8PubMedCrossRefGoogle Scholar
  129. 129.
    Kurth MC, Tetrad JW, Tanner CM, et al. Double-blind, placebo-controlled, crossover study of duodenal infusion of levodopa/carbidopa in Parkinson’s disease patients with ‘on-off’ fluctuations. Neurology 1993; 43: 1698–703PubMedCrossRefGoogle Scholar
  130. 130.
    The Parkinson Study Group. A controlled trial of rotigotine monotherapy in early Parkinson’s disease. Arch Neurol 2003; 60: 1721–8CrossRefGoogle Scholar
  131. 131.
    Watts RL, Jankovic J, Waters C, et al. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology 2007; 68: 272–6PubMedCrossRefGoogle Scholar
  132. 132.
    LeWitt PA, Lyons KE, Pahwa R. Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. The SP 650 Study Group. Neurology 2007; 68: 1262–7Google Scholar
  133. 133.
    Guttman M. Double-blind comparison of pramipexole and bromocriptine treatment with placebo in advanced Parkinson’s disease. International Pramipexole-Bromocriptine Study Group. Neurology 1997; 49: 1060–5Google Scholar
  134. 134.
    Mizuno Y, Yanagisawa N, Kuno S, et al. Randomized, double-blind study of pramipexole with placebo and bromocriptine in advanced Parkinson’s disease. The Japanese Pramipexole Study Group. Mov Disord 2003; 18: 1149–56CrossRefGoogle Scholar
  135. 135.
    Pinter MM, Pogarell O, Oertel WH. Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson’s disease: a double blind, placebo controlled, randomised, multicentre study. J Neurol Neurosurg Psychiatry 1999; 66: 436–41PubMedCrossRefGoogle Scholar
  136. 136.
    Moller JC, Oertel WH, Koster J, et al. Long-term efficacy and safety of pramipexole in advanced Parkinson’s disease: results from a European multicenter trial. Mov Disord 2005; 20: 602–10PubMedCrossRefGoogle Scholar
  137. 137.
    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. Depression/Parkinson Italian Study Group. J Neurol 2006; 253: 601–7Google Scholar
  138. 138.
    Noyes K, Dick AW, Holloway RG. Pramipexole versus levodopa in patients with early Parkinson’s disease: effect on generic and disease-specific quality of life. Parkinson Study Group. Value Health 2006; 9: 28–38Google Scholar
  139. 139.
    Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson disease: a randomized controlled trial. Parkinson Study Group. JAMA 2000; 284(15): 1931–8Google Scholar
  140. 140.
    Brooks DJ, Abbott RJ, Lees AJ, et al. A placebo-controlled evaluation of ropinirole, a novel D2 agonist, as sole dopaminergic therapy in Parkinson’s disease. Clin Neuropharmacol 1998; 21: 101–7PubMedGoogle Scholar
  141. 141.
    Sethi KD, O’Brien CF, Hammerstad JP, et al. Ropinirole for the treatment of early Parkinson disease: a 12-month experience. The Ropinirole Study Group. Arch Neurol 1998; 55: 1211–6Google Scholar
  142. 142.
    Mizuno Y, Abe T, Hasegawa K, et al. Ropinirole is effective on motor function when used as an adjunct to levodopa in Parkinson’s disease: STRONG study. Mov Disord 2007; 22: 1860–5PubMedCrossRefGoogle Scholar
  143. 143.
    Rascol O, Dubois B, Caldas AC, et al. Early piribedil monotherapy of Parkinson’s disease: a planned seven-month report of the REGAIN study. Parkinson REGAIN Study Group. Mov Disord 2006; 21(12): 2110–5Google Scholar
  144. 144.
    Suwantamee J, Nidhinandana S, Srisuwananukorn S, et al. Efficacy and safety of piribedil in early combination with L-dopa in the treatment of Parkinson’s disease: a 6-month open study. J Med Assoc Thai 2004; 87(11): 1293–300PubMedGoogle Scholar
  145. 145.
    Evidente VG, Esteban RP, Domingo FM, et al. Piribedil as an adjunct to levodopa in advanced Parkinson’s disease: the Asian experience. Parkinsonism Relat Disord 2003; 10(2): 117–21PubMedCrossRefGoogle Scholar
  146. 146.
    Salazar Tortolero G, Wix Ramos R, Salazar Aladren P, et al. The effectiveness and tolerance of piribedil as adjunct therapy to levodopa in patients with Parkinson’s disease: a nine month follow up [in Spanish]. Rev Neurol 2004; 38(8): 715–9PubMedGoogle Scholar
  147. 147.
    Corrigan MH, Denahan AQ, Wright CE, et al. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety 2000; 11: 58–65PubMedCrossRefGoogle Scholar
  148. 148.
    Zarate Jr CA, Payne JL, Singh J, et al. Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry 2004; 56: 54–60PubMedCrossRefGoogle Scholar
  149. 149.
    Goldberg JF, Burdick KE, Endick CJ. Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry 2004; 161: 564–6PubMedCrossRefGoogle Scholar
  150. 150.
    Cassano P, Lattanzi L, Soldani F, et al. Pramipexole in treatment-resistant depression: an extended follow-up. Depress Anxiety 2004; 20: 131–8PubMedCrossRefGoogle Scholar
  151. 151.
    Lattanzi L, Dell’Osso L, Cassano P, et al. Pramipexole in treatment-resistant depression: a 16-week naturalistic study. Bipolar Disord 2002; 4: 307–14PubMedCrossRefGoogle Scholar
  152. 152.
    Lemke MR, Brecht HM, Koester J, et al. Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson’s disease. J Neurol Sci 2006; 248: 266–70PubMedCrossRefGoogle Scholar
  153. 153.
    Rektorova I, Rektor I, Bares M, et al. Cognitive performance in people with Parkinson’s disease and mild or moderate depression: effects of dopamine agonists in an add-on to L-dopa therapy. Eur J Neurol 2005; 12: 9–15PubMedCrossRefGoogle Scholar
  154. 154.
    Snaith RP, Hamilton M, Morley S, et al. A scale for the assessment of hedonic tone: the Snaith-Hamilton Pleasure Scale. Br J Psychiatry 1995; 167: 99–103PubMedCrossRefGoogle Scholar
  155. 155.
    Cassano P, Lattanzi L, Fava M, et al. Ropinirole in treatment-resistant depression: a 16-week pilot study. Can J Psychiatry 2005; 50: 357–60PubMedGoogle Scholar
  156. 156.
    Perugi G, Toni C, Ruffolo G, et al. Adjunctive dopamine agonists in treatment-resistant bipolar II depression: an open case series. Pharmacopsychiatry 2001; 34: 137–41PubMedCrossRefGoogle Scholar
  157. 157.
    Bertaina-Anglade V, La Rochelle CD, Scheller DK. Antidepressant properties of rotigotine in experimental models of depression. Eur J Pharmacol 2006; 548: 106–14PubMedCrossRefGoogle Scholar
  158. 158.
    Mentenopoulos G, Katsarou Z, Bostantjopoulou S, et al. Piribedil therapy in Parkinson’s disease: use of the drug in the retard form. Clin Neuropharmacol 1989; 12(1): 23–8PubMedCrossRefGoogle Scholar
  159. 159.
    Rondot P, Ziegler M. Activity and acceptability of piribedil in Parkinson’s disease: a multicentre study. J Neurol 1992; 239Suppl. 1: S28–34PubMedGoogle Scholar
  160. 160.
    Ziegler M, Rondot P. Action of piribedil in Parkinson disease: multicenter study [in French]. Presse Med 1999; 28(26): 1414–8PubMedGoogle Scholar
  161. 161.
    Post RM, Gerner RH, Carman JS, et al. Effects of a dopamine agonist piribedil in depressed patients: relationship of pretreatment homovanillic acid to antidepressant response. Arch Gen Psychiatry 1978; 35(5): 609–15PubMedCrossRefGoogle Scholar
  162. 162.
    Elmer L, Schwid S, Eberly S, et al. Rasagiline-associated motor improvement in PD occurs without worsening of cognitive and behavioral symptoms. Parkinson Study Group TEMPO and PRESTO Investigators. J Neurol Sci 2006; 248: 78–83Google Scholar
  163. 163.
    Brooks DJ, Sagar H. Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson’s disease: a randomised, placebo controlled, double blind, six month study. UK-Irish Entacapone Study Group. J Neurol Neurosurg Psychiatry 2003; 74: 1071–9Google Scholar
  164. 164.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
  165. 165.
    Fava M, Rosenbaum JF, Kolsky AR, et al. Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder. J Clin Psychopharmacol 1999; 19: 329–35PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Department of Clinical NeurosciencesRoyal Free and University College Medical School, University College LondonLondonEngland
  2. 2.Institute of NeurologyUniversity College LondonLondonEngland

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