What is the best initial treatment of Parkinson’s disease?

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What is the best initial treatment of Parkinson’s disease?
EVIDENCE-BASED ANSWER

No studies clearly demonstrate the best initial treatment for Parkinson’s disease. Levodopa improves motor function in Parkinson’s disease; however, long-term use is associated with irreversible dyskinesias and motor fluctuations. Compared with placebo, selegiline improves the motor symptoms of Parkinson’s disease and allows a physician to delay the introduction of levodopa by 9 to 12 months (strength of recommendation [SOR]: A, based on randomized controlled trials).

Dopamine agonists—alone or combined with levodopa—have fewer associated dyskinesias and other motor complications but produce lower scores on activities of daily living and Unified Parkinson’s Disease Rating Scale (UPDRS) when compared with levodopa alone (SOR: A, based on systematic reviews of randomized controlled trials). Drug choices should be based on each patient’s individual symptoms and response to medication (Table).

TABLE
Medications for Parkinson’s disease

MedicationStarting doseUsual daily doseApprox cost/mo
Selegiline5 mg every morning5 mg every morning and at noon$29 for 10 mg/d
Carbidopa/levodopa25/100 mg tab 3 times daily25/100 mg 3 times daily$76 for 75/300 mg/d
Pergolide0.05 mg/d2–3 mg/d divided 3 times daily$223 for 2 mg/d
Pramipexole0.375 mg/d divided 3 times daily1.5–4.5 mg/d divided 3 times daily$177 for 3 mg/d
Ropinirole0.25 mg 3 times daily3 mg divided 3 times daily$185 for 3 mg/d
 

Evidence summary

Five randomized controlled trials15 have shown improved motor function and activities of daily living with selegiline vs placebo in early Parkinson’s disease. Two of these trials1,2 found that selegiline delayed the need for levodopa for 9 to 12 months.

One large randomized controlled trial showed no difference in disability scores and an increase in mortality at 5.6 years when comparing selegiline combined with levodopa to levodopa alone.6 A re-analysis of this study, as well as subsequent studies, have not supported this conclusion and found no increase in mortality in patients with a history of selegiline use.7-10

Two Cochrane reviews found that patients who tolerated the dopamine agonist bromocriptine—when administered alone or with levodopa—had delayed dyskinesias and motor complications compared with levodopa alone.11,12 There was no change in off-time with the combination.12 A large randomized controlled trial comparing bromocriptine with levodopa demonstrated that at 3 years, disability scores were lower in the patients initially assigned to bromocriptine, but the difference was no longer significant at 9 years.13

The bromocriptine group in this trial showed a lower incidence of dyskinesias when data from all patient groups were combined. However, when moderate to severe cases were analyzed separately, there was no significant difference.13 There was no difference in mortality between patients initially treated with bromocriptine vs levodopa.13,14

Studies of other dopamine agonists show results comparable with bromocriptine. Lisuride (not available in the US) with rescue levodopa vs levodopa alone had fewer motor complications at 4 years but lower UPDRS and activities of daily living scores.15 Another study comparing lisuride (with or without levodopa) vs levodopa alone found no difference in motor complications at 5 years.16 Studies with cabergoline, pramipexole, and pergolide—alone or combined with levodopa—vs levodopa alone showed a decrease in motor complications with the dopamine agonist but lower activities of daily living and UPDRS scores.17-19

Recommendations from others

In 2002, the American Academy of Neurology published practice parameters for the initiation of treatment for Parkinson’s disease based on literature from 1966 to 1999. The authors concluded:

  • selegiline has mild symptomatic benefit and may be tried as initial therapy, but confers no neuroprotective effect
  • either levodopa or a dopamine agonist can be used for the initial treatment of symptomatic Parkinson’s disease
  • levodopa has a higher risk of dyskinesias than a dopamine agonist but superior motor benefits,20 and is less likely to have other side effects (nausea, hallucinations, somnolence, and edema).
CLINICAL COMMENTARY

Family physicians play a key role in monitoring Parkinson’s
Randy Ward, MD
Medical College of Wisconsin, Milwaukee

Parkinson’s disease has a profound impact on a patient’s physical and psychological wellbeing. Difficulties with movement, autonomic nervous system abnormalities, neuropsychiatric symptoms, and problems with medication effectiveness and side effects all occur throughout its course. Consultation with a neurologist skilled in this disorder can be quite helpful, particularly in younger patients or when the diagnosis is unclear. The family physician plays a key role in monitoring of the patient’s condition. Active management of symptoms (and comorbidities as they arise) is crucial in helping patients maintain their functional status and quality of life.

References

1. Myllyla VV, Sotaniemi KA, Vuorinen JA, Heinonen EH. Selegiline as initial treatment in de novo parkinsonian patients. Neurology 1992;42:339-343.

2. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. The Parkinson Study Group. N Engl J Med 1993;328:176-183.

3. Olanow CW, Hauser RA, Gauger L, et al. The effect of deprenyl and levodopa on the progression of Parkinson’s disease. Ann Neurol 1995;38:771-777.

4. Larsen JP, Boas J, Erdal JE. Does selegiline modify the progression of early Parkinson’s disease? Results from a five-year study. The Norwegian-Danish Study Group. Eur J Neurol 1999;6:539-547.

5. Przuntek H, Conrad B, Dichgans J, et al. SELEDO: a 5-year long-term trial on the effect of selegiline in early Parkinsonian patients treated with levodopa. Eur J Neurol 1999;6:141-150.

6. Lees AJ. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in people with early, mild Parkinson’s disease. Parkinson’s Disease Research Group of the United Kingdom. BMJ 1995;311:1602-1607.

7. Counsell C. Effect of adding selegiline to levodopa in early, mild Parkinson’s disease. Formal systematic review of data on patients in all relevant trials is required. BMJ 1998;17:1586.-

8. Ben-Shlomo Y, Churchyard A, Head J, et al. Investigation by Parkinson’s Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson’s disease: further results of randomised trial and confidential inquiry. BMJ 1998;316:1191-1196.

9. Olanow CW, Myllyla VV, Sotaniemi K, et al. Effect of selegiline on mortality in patients with Parkinson’s disease: a meta-analysis. Neurology 1998;51:825-830.

10. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP patients requiring levodopa. Parkinson Study Group. Ann Neurol 1996;39:37-45.

11. Ramaker C, van Hilten JJ. Bromocriptine versus levodopa in early Parkinson’s disease. The Cochrane Library, Issue 3, 2003. Oxford: Update Software, last updated February 2, 2000. Accessed on April 15, 2003.

12. Ramaker C, van Hilten JJ. Bromocriptine/levodopa combined versus levodopa alone for early Parkinson’s disease (Cochrane Review). The Cochrane Library, Issue 3, 2003. Oxford: Update Software, last updated October 21, 2001. Accessed on April 15, 2003.

13. Lees AJ, Katzenschlager R, Head J, Ben-Shlomo Y. Ten-year follow-up of three different initial treatments in de-novo PD: A randomized trial. Neurology 2001;57:1687-1694.

14. Hely MA, Morris JG, Traficante R, et al. The Sydney multicentre study of Parkinson’s disease: progression and mortality at 10 years. J Neurol Neurosurg Psychiatry 1999;67:300-307.

15. Rinne UK. Lisuride, a dopamine agonist in the treatment of early Parkinson’s disease. Neurology 1989;39:336-339.

16. Allain H, Destee A, Petit H, et al. Five-year follow-up of early lisuride and levodopa combination therapy versus levodopa monotherapy in de novo Parkinson’s disease. The French Lisuride Study Group. Eur Neurol 2000;44:22-30.

17. Rinne U. A 5-year double-blind study with cabergoline versus levodopa in the treatment of early Parkinson’s disease. Parkinsonism Relat Disord 1999;5(suppl):84.-

18. Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial. Parkinson Study Group. JAMA 2000;284:1931-1938.

19. Oertel W. Pergolide or levodopa for Parkinson’s therapy? 6th International Congress of Parkinson’s Disease and Movement Disorders, June 11–15, 2000. Available at: http://www.parkinsonsdisease.com/news/N100_arc.HTM #Pergolide. Accessed on April 15, 2003.

20. Miyasaki JM, Martin W, Suchowersky O, Weiner WJ, Lang AE. Practice parameter: initiation of treatment for Parkinson’s disease: An evidence-based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2002;58:11-17.

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Gary Kelsberg, MD
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University of Washington Health Sciences Libraries, Seattle

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Gary Kelsberg, MD
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University of Washington Health Sciences Libraries, Seattle

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Gary Kelsberg, MD
Valley Medical Center Family Practice Residency, Renton, Wash

Joanne Rich, BSc (Pharm), MLIS
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EVIDENCE-BASED ANSWER

No studies clearly demonstrate the best initial treatment for Parkinson’s disease. Levodopa improves motor function in Parkinson’s disease; however, long-term use is associated with irreversible dyskinesias and motor fluctuations. Compared with placebo, selegiline improves the motor symptoms of Parkinson’s disease and allows a physician to delay the introduction of levodopa by 9 to 12 months (strength of recommendation [SOR]: A, based on randomized controlled trials).

Dopamine agonists—alone or combined with levodopa—have fewer associated dyskinesias and other motor complications but produce lower scores on activities of daily living and Unified Parkinson’s Disease Rating Scale (UPDRS) when compared with levodopa alone (SOR: A, based on systematic reviews of randomized controlled trials). Drug choices should be based on each patient’s individual symptoms and response to medication (Table).

TABLE
Medications for Parkinson’s disease

MedicationStarting doseUsual daily doseApprox cost/mo
Selegiline5 mg every morning5 mg every morning and at noon$29 for 10 mg/d
Carbidopa/levodopa25/100 mg tab 3 times daily25/100 mg 3 times daily$76 for 75/300 mg/d
Pergolide0.05 mg/d2–3 mg/d divided 3 times daily$223 for 2 mg/d
Pramipexole0.375 mg/d divided 3 times daily1.5–4.5 mg/d divided 3 times daily$177 for 3 mg/d
Ropinirole0.25 mg 3 times daily3 mg divided 3 times daily$185 for 3 mg/d
 

Evidence summary

Five randomized controlled trials15 have shown improved motor function and activities of daily living with selegiline vs placebo in early Parkinson’s disease. Two of these trials1,2 found that selegiline delayed the need for levodopa for 9 to 12 months.

One large randomized controlled trial showed no difference in disability scores and an increase in mortality at 5.6 years when comparing selegiline combined with levodopa to levodopa alone.6 A re-analysis of this study, as well as subsequent studies, have not supported this conclusion and found no increase in mortality in patients with a history of selegiline use.7-10

Two Cochrane reviews found that patients who tolerated the dopamine agonist bromocriptine—when administered alone or with levodopa—had delayed dyskinesias and motor complications compared with levodopa alone.11,12 There was no change in off-time with the combination.12 A large randomized controlled trial comparing bromocriptine with levodopa demonstrated that at 3 years, disability scores were lower in the patients initially assigned to bromocriptine, but the difference was no longer significant at 9 years.13

The bromocriptine group in this trial showed a lower incidence of dyskinesias when data from all patient groups were combined. However, when moderate to severe cases were analyzed separately, there was no significant difference.13 There was no difference in mortality between patients initially treated with bromocriptine vs levodopa.13,14

Studies of other dopamine agonists show results comparable with bromocriptine. Lisuride (not available in the US) with rescue levodopa vs levodopa alone had fewer motor complications at 4 years but lower UPDRS and activities of daily living scores.15 Another study comparing lisuride (with or without levodopa) vs levodopa alone found no difference in motor complications at 5 years.16 Studies with cabergoline, pramipexole, and pergolide—alone or combined with levodopa—vs levodopa alone showed a decrease in motor complications with the dopamine agonist but lower activities of daily living and UPDRS scores.17-19

Recommendations from others

In 2002, the American Academy of Neurology published practice parameters for the initiation of treatment for Parkinson’s disease based on literature from 1966 to 1999. The authors concluded:

  • selegiline has mild symptomatic benefit and may be tried as initial therapy, but confers no neuroprotective effect
  • either levodopa or a dopamine agonist can be used for the initial treatment of symptomatic Parkinson’s disease
  • levodopa has a higher risk of dyskinesias than a dopamine agonist but superior motor benefits,20 and is less likely to have other side effects (nausea, hallucinations, somnolence, and edema).
CLINICAL COMMENTARY

Family physicians play a key role in monitoring Parkinson’s
Randy Ward, MD
Medical College of Wisconsin, Milwaukee

Parkinson’s disease has a profound impact on a patient’s physical and psychological wellbeing. Difficulties with movement, autonomic nervous system abnormalities, neuropsychiatric symptoms, and problems with medication effectiveness and side effects all occur throughout its course. Consultation with a neurologist skilled in this disorder can be quite helpful, particularly in younger patients or when the diagnosis is unclear. The family physician plays a key role in monitoring of the patient’s condition. Active management of symptoms (and comorbidities as they arise) is crucial in helping patients maintain their functional status and quality of life.

EVIDENCE-BASED ANSWER

No studies clearly demonstrate the best initial treatment for Parkinson’s disease. Levodopa improves motor function in Parkinson’s disease; however, long-term use is associated with irreversible dyskinesias and motor fluctuations. Compared with placebo, selegiline improves the motor symptoms of Parkinson’s disease and allows a physician to delay the introduction of levodopa by 9 to 12 months (strength of recommendation [SOR]: A, based on randomized controlled trials).

Dopamine agonists—alone or combined with levodopa—have fewer associated dyskinesias and other motor complications but produce lower scores on activities of daily living and Unified Parkinson’s Disease Rating Scale (UPDRS) when compared with levodopa alone (SOR: A, based on systematic reviews of randomized controlled trials). Drug choices should be based on each patient’s individual symptoms and response to medication (Table).

TABLE
Medications for Parkinson’s disease

MedicationStarting doseUsual daily doseApprox cost/mo
Selegiline5 mg every morning5 mg every morning and at noon$29 for 10 mg/d
Carbidopa/levodopa25/100 mg tab 3 times daily25/100 mg 3 times daily$76 for 75/300 mg/d
Pergolide0.05 mg/d2–3 mg/d divided 3 times daily$223 for 2 mg/d
Pramipexole0.375 mg/d divided 3 times daily1.5–4.5 mg/d divided 3 times daily$177 for 3 mg/d
Ropinirole0.25 mg 3 times daily3 mg divided 3 times daily$185 for 3 mg/d
 

Evidence summary

Five randomized controlled trials15 have shown improved motor function and activities of daily living with selegiline vs placebo in early Parkinson’s disease. Two of these trials1,2 found that selegiline delayed the need for levodopa for 9 to 12 months.

One large randomized controlled trial showed no difference in disability scores and an increase in mortality at 5.6 years when comparing selegiline combined with levodopa to levodopa alone.6 A re-analysis of this study, as well as subsequent studies, have not supported this conclusion and found no increase in mortality in patients with a history of selegiline use.7-10

Two Cochrane reviews found that patients who tolerated the dopamine agonist bromocriptine—when administered alone or with levodopa—had delayed dyskinesias and motor complications compared with levodopa alone.11,12 There was no change in off-time with the combination.12 A large randomized controlled trial comparing bromocriptine with levodopa demonstrated that at 3 years, disability scores were lower in the patients initially assigned to bromocriptine, but the difference was no longer significant at 9 years.13

The bromocriptine group in this trial showed a lower incidence of dyskinesias when data from all patient groups were combined. However, when moderate to severe cases were analyzed separately, there was no significant difference.13 There was no difference in mortality between patients initially treated with bromocriptine vs levodopa.13,14

Studies of other dopamine agonists show results comparable with bromocriptine. Lisuride (not available in the US) with rescue levodopa vs levodopa alone had fewer motor complications at 4 years but lower UPDRS and activities of daily living scores.15 Another study comparing lisuride (with or without levodopa) vs levodopa alone found no difference in motor complications at 5 years.16 Studies with cabergoline, pramipexole, and pergolide—alone or combined with levodopa—vs levodopa alone showed a decrease in motor complications with the dopamine agonist but lower activities of daily living and UPDRS scores.17-19

Recommendations from others

In 2002, the American Academy of Neurology published practice parameters for the initiation of treatment for Parkinson’s disease based on literature from 1966 to 1999. The authors concluded:

  • selegiline has mild symptomatic benefit and may be tried as initial therapy, but confers no neuroprotective effect
  • either levodopa or a dopamine agonist can be used for the initial treatment of symptomatic Parkinson’s disease
  • levodopa has a higher risk of dyskinesias than a dopamine agonist but superior motor benefits,20 and is less likely to have other side effects (nausea, hallucinations, somnolence, and edema).
CLINICAL COMMENTARY

Family physicians play a key role in monitoring Parkinson’s
Randy Ward, MD
Medical College of Wisconsin, Milwaukee

Parkinson’s disease has a profound impact on a patient’s physical and psychological wellbeing. Difficulties with movement, autonomic nervous system abnormalities, neuropsychiatric symptoms, and problems with medication effectiveness and side effects all occur throughout its course. Consultation with a neurologist skilled in this disorder can be quite helpful, particularly in younger patients or when the diagnosis is unclear. The family physician plays a key role in monitoring of the patient’s condition. Active management of symptoms (and comorbidities as they arise) is crucial in helping patients maintain their functional status and quality of life.

References

1. Myllyla VV, Sotaniemi KA, Vuorinen JA, Heinonen EH. Selegiline as initial treatment in de novo parkinsonian patients. Neurology 1992;42:339-343.

2. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. The Parkinson Study Group. N Engl J Med 1993;328:176-183.

3. Olanow CW, Hauser RA, Gauger L, et al. The effect of deprenyl and levodopa on the progression of Parkinson’s disease. Ann Neurol 1995;38:771-777.

4. Larsen JP, Boas J, Erdal JE. Does selegiline modify the progression of early Parkinson’s disease? Results from a five-year study. The Norwegian-Danish Study Group. Eur J Neurol 1999;6:539-547.

5. Przuntek H, Conrad B, Dichgans J, et al. SELEDO: a 5-year long-term trial on the effect of selegiline in early Parkinsonian patients treated with levodopa. Eur J Neurol 1999;6:141-150.

6. Lees AJ. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in people with early, mild Parkinson’s disease. Parkinson’s Disease Research Group of the United Kingdom. BMJ 1995;311:1602-1607.

7. Counsell C. Effect of adding selegiline to levodopa in early, mild Parkinson’s disease. Formal systematic review of data on patients in all relevant trials is required. BMJ 1998;17:1586.-

8. Ben-Shlomo Y, Churchyard A, Head J, et al. Investigation by Parkinson’s Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson’s disease: further results of randomised trial and confidential inquiry. BMJ 1998;316:1191-1196.

9. Olanow CW, Myllyla VV, Sotaniemi K, et al. Effect of selegiline on mortality in patients with Parkinson’s disease: a meta-analysis. Neurology 1998;51:825-830.

10. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP patients requiring levodopa. Parkinson Study Group. Ann Neurol 1996;39:37-45.

11. Ramaker C, van Hilten JJ. Bromocriptine versus levodopa in early Parkinson’s disease. The Cochrane Library, Issue 3, 2003. Oxford: Update Software, last updated February 2, 2000. Accessed on April 15, 2003.

12. Ramaker C, van Hilten JJ. Bromocriptine/levodopa combined versus levodopa alone for early Parkinson’s disease (Cochrane Review). The Cochrane Library, Issue 3, 2003. Oxford: Update Software, last updated October 21, 2001. Accessed on April 15, 2003.

13. Lees AJ, Katzenschlager R, Head J, Ben-Shlomo Y. Ten-year follow-up of three different initial treatments in de-novo PD: A randomized trial. Neurology 2001;57:1687-1694.

14. Hely MA, Morris JG, Traficante R, et al. The Sydney multicentre study of Parkinson’s disease: progression and mortality at 10 years. J Neurol Neurosurg Psychiatry 1999;67:300-307.

15. Rinne UK. Lisuride, a dopamine agonist in the treatment of early Parkinson’s disease. Neurology 1989;39:336-339.

16. Allain H, Destee A, Petit H, et al. Five-year follow-up of early lisuride and levodopa combination therapy versus levodopa monotherapy in de novo Parkinson’s disease. The French Lisuride Study Group. Eur Neurol 2000;44:22-30.

17. Rinne U. A 5-year double-blind study with cabergoline versus levodopa in the treatment of early Parkinson’s disease. Parkinsonism Relat Disord 1999;5(suppl):84.-

18. Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial. Parkinson Study Group. JAMA 2000;284:1931-1938.

19. Oertel W. Pergolide or levodopa for Parkinson’s therapy? 6th International Congress of Parkinson’s Disease and Movement Disorders, June 11–15, 2000. Available at: http://www.parkinsonsdisease.com/news/N100_arc.HTM #Pergolide. Accessed on April 15, 2003.

20. Miyasaki JM, Martin W, Suchowersky O, Weiner WJ, Lang AE. Practice parameter: initiation of treatment for Parkinson’s disease: An evidence-based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2002;58:11-17.

References

1. Myllyla VV, Sotaniemi KA, Vuorinen JA, Heinonen EH. Selegiline as initial treatment in de novo parkinsonian patients. Neurology 1992;42:339-343.

2. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. The Parkinson Study Group. N Engl J Med 1993;328:176-183.

3. Olanow CW, Hauser RA, Gauger L, et al. The effect of deprenyl and levodopa on the progression of Parkinson’s disease. Ann Neurol 1995;38:771-777.

4. Larsen JP, Boas J, Erdal JE. Does selegiline modify the progression of early Parkinson’s disease? Results from a five-year study. The Norwegian-Danish Study Group. Eur J Neurol 1999;6:539-547.

5. Przuntek H, Conrad B, Dichgans J, et al. SELEDO: a 5-year long-term trial on the effect of selegiline in early Parkinsonian patients treated with levodopa. Eur J Neurol 1999;6:141-150.

6. Lees AJ. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in people with early, mild Parkinson’s disease. Parkinson’s Disease Research Group of the United Kingdom. BMJ 1995;311:1602-1607.

7. Counsell C. Effect of adding selegiline to levodopa in early, mild Parkinson’s disease. Formal systematic review of data on patients in all relevant trials is required. BMJ 1998;17:1586.-

8. Ben-Shlomo Y, Churchyard A, Head J, et al. Investigation by Parkinson’s Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson’s disease: further results of randomised trial and confidential inquiry. BMJ 1998;316:1191-1196.

9. Olanow CW, Myllyla VV, Sotaniemi K, et al. Effect of selegiline on mortality in patients with Parkinson’s disease: a meta-analysis. Neurology 1998;51:825-830.

10. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP patients requiring levodopa. Parkinson Study Group. Ann Neurol 1996;39:37-45.

11. Ramaker C, van Hilten JJ. Bromocriptine versus levodopa in early Parkinson’s disease. The Cochrane Library, Issue 3, 2003. Oxford: Update Software, last updated February 2, 2000. Accessed on April 15, 2003.

12. Ramaker C, van Hilten JJ. Bromocriptine/levodopa combined versus levodopa alone for early Parkinson’s disease (Cochrane Review). The Cochrane Library, Issue 3, 2003. Oxford: Update Software, last updated October 21, 2001. Accessed on April 15, 2003.

13. Lees AJ, Katzenschlager R, Head J, Ben-Shlomo Y. Ten-year follow-up of three different initial treatments in de-novo PD: A randomized trial. Neurology 2001;57:1687-1694.

14. Hely MA, Morris JG, Traficante R, et al. The Sydney multicentre study of Parkinson’s disease: progression and mortality at 10 years. J Neurol Neurosurg Psychiatry 1999;67:300-307.

15. Rinne UK. Lisuride, a dopamine agonist in the treatment of early Parkinson’s disease. Neurology 1989;39:336-339.

16. Allain H, Destee A, Petit H, et al. Five-year follow-up of early lisuride and levodopa combination therapy versus levodopa monotherapy in de novo Parkinson’s disease. The French Lisuride Study Group. Eur Neurol 2000;44:22-30.

17. Rinne U. A 5-year double-blind study with cabergoline versus levodopa in the treatment of early Parkinson’s disease. Parkinsonism Relat Disord 1999;5(suppl):84.-

18. Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial. Parkinson Study Group. JAMA 2000;284:1931-1938.

19. Oertel W. Pergolide or levodopa for Parkinson’s therapy? 6th International Congress of Parkinson’s Disease and Movement Disorders, June 11–15, 2000. Available at: http://www.parkinsonsdisease.com/news/N100_arc.HTM #Pergolide. Accessed on April 15, 2003.

20. Miyasaki JM, Martin W, Suchowersky O, Weiner WJ, Lang AE. Practice parameter: initiation of treatment for Parkinson’s disease: An evidence-based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2002;58:11-17.

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