Bromocriptine versus levodopa in early Parkinson's disease

van Hilten; Claudia C Ramaker; Rebecca Stowe; Natalie Ives

doi:10.1002/14651858.CD002258.pub2

Bromocriptina versus levodopa en la enfermedad de Parkinson temprana

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Referencias

Referencias de los estudios incluidos en esta revisión

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estudios excluidos
otras referencias

Hely MA, Morris JG, Rail D, O'Sullivan DJ, Williamson PM, Genge S, et al. The Sydney multicentre study of Parkinson's disease: The first 18 months. The Medical Journal of Australia 1987;146:195‐8.

Hely MA, Morris JG, Rail D, Reid WG, O'Sullivan DJ, Willaimson PM, et al. The Sydney Multicentre Study of Parkinson's disease: a report on the first 3 years. Journal of Neurology, Neurosurgery, and Psychiatry 1989;52:324‐8.

Hely MA, Morris JGL, Reid WGJ, O'Sullivan DJ, Williamson PM, Rail D, et al. The Sydney Multicentre Study of Parkinson's disease: a randomised, prospective five year study comparing with low dose bromocriptine with low dose levodopa‐carbidopa. Journal of Neurology, Neurosurgery, and Psychiatry 1994;57:903‐10.

Herskovits E, Yorio A, Leston J. Long term bromocriptine treatment in de novo Parkinsonian patients. Medicina (B Aires) 1988;48(4):345‐50.

Olanow CW, Alberts MJ, Stajich J, Burch G. A randomized blinded study of low‐dose bromocriptine versus low‐dose carbidopa/levodopa in untreated Parkinson's patients. In: Fahn S, Marsden D, Calne D, Goldstein M editor(s). Recent developments in Parkinson's disease. Vol. II, New York: Macmillan Healthcare, 1987:201‐208.

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Riopelle RJ, Gawel MJ, Libman I, King DB, McLean DR, Paulseth R, et al. A double‐blind study of bromocriptine and L‐dopa in de novo Parkinson's disease. Short term results. European Neurology 1988;28 Suppl 1:11‐4.

Lees AJ, Frankel J, Eatough V, Stern GM. New approaches in the use of selegiline for the treatment of Parkinson's disease. Acta Neurologica Scandinavica. Supplementum 1989;126:139‐45.

Lees AJ. Comparison of therapeutic effects, mortality data of levodopa, levodopa combined with selegiline in patients with early. mild Parkinson's disease. Parkinson's Disease Research Group of the United Kingdom. BMJ 1995;311:1602‐7.

Parkinson's Disease Research Group in the United Kingdom. Comparisons of therapeutic effects of levodopa, levodopa and selegiline, and bromocriptine in patients with early, mild Parkinson's disease: three year interim report. BMJ 1993;307:469‐72.

Weiner WJ, Factor SA, Sanchez‐Ramos JR, Singer C, Sheldon RN, Cornelius L, et al. Early combination therapy (bromocriptine and levodopa) does not prevent motor fluctuations in Parkinson's disease. Neurology 1993;43(1):21‐7.

Referencias de los estudios excluidos de esta revisión

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estudios incluidos
otras referencias

Caraceni T, Musicco M. Levodopa or dopamine agonists, or deprenyl as initial treatment for Parkinson's disease. A randomized multicentre study. Parkinsonism and Related Disorders 2001;107:107‐14.

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Libman I, Gawel MJ, Riopelle RJ, Bouchard S. A comparison of bromocriptine (Parlodel) and levodopa‐carbidopa (Sinemet) for treatment of "de novo" Parkinson's disease patients. The Canadian Journal of Neurological Sciences 1987;14:576‐80.

Riopelle RJ. Bromocriptine and the clinical spectrum of Parkinson's disease. The Canadian Journal of Neurological Sciences 1987;14(Suppl):S455‐S9.

Wallis WE. A progress report on the New Zealand Multicentre Parkinson's disease trial. A comparison of low‐dose treatment with bromocriptine or L‐dopa. European Neurology 1988;28(Suppl 1):S9‐S10.

Referencias adicionales

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estudios excluidos

Ahlskog JE. Treatment of Parkinson's disease. From theory to practice. Postgraduate Medicine 1994;95:52‐4.

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

Hely 1994

Methods	Randomised: randomisation tables. 'Double blind': only in titration phase. Duration: 5 years (on going), including a 6‐month dose titration.
Participants	Country: Australia. Centres: 4. Inclusion criteria: idiopathic PD, receiving no or less than 3 months LD. Exclusion criteria: NA. No. Randomised: 149. Excluded patients: 13 revised diagnoses and 10 failed to complete dose titration phase. Mean age: 62 years (BR), 62 years (LD). Female:Male = 56:70. Mean disease duration: 22 months (BR), 25 months (LD).
Interventions	1) BR monotherapy (start: 1mg/day increased at weekly, then monthly intervals to a max. of 30 mg/day after 40 weeks) [62]. Mean dose: 32 mg/day, range 7.5‐60 mg/day. 2) LD/carbidopa monotherapy (start: 20/5 mg/day LD increased at weekly, then monthly intervals to a max. of 600/150 mg LD after 40 weeks) [64]. Mean dose: 475 mg/day, range 300‐600 mg/day.
Outcomes	Dyskinesias: significant more in LD‐group at 1‐2‐3‐4‐5 year(s). Dystonia: significant more in LD‐group at 1‐2‐3‐4‐5 year(s). Wearing‐off: significant more in BR‐group at 2 years and significant more in LD‐group at 4‐5 years. On‐off fluctuations: 1 patient in the LD‐group at 5 years. IMP: mod. CURS: NS. DIS: mod. NUDS: NS.
Notes	LD:carbidopa = 4:1. Trial design allowed switching from or addition of therapy. Dropouts: 20 (BR), 11 (LD).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Herskovits 1988

Methods	Randomised: unclear. 'Single blind'. Duration: follow up varied between 18‐45 months.
Participants	Country: Argentina. Centres: NA. Inclusion criteria: recently diagnosed idiopathic PD, prior to trial not receiving any antiparkinsonian medication. No. Randomised: 86. BR/LD combination treatment: 31. Mean age: 67.5 years. Female:Male = 52:34. Mean disease duration: NA.
Interventions	1) BR monotherapy (start: 1.25 mg/day increased with 1.25 mg/day to a max. of 15 mg/day) [26]. Mean daily dose: 12.6 mg, range: 7.5‐20 mg. 2) LD/carbidopa monotherapy (start: 125/12.5 mg/day increased with 125/12.5 mg [29]. Mean daily dose: 556.1 mg, range: 250‐625 mg.
Outcomes	Dyskinesias: 1 patient on a low dose of BR and 1 patient in the LD‐group. Dystonia: 2 patients in the LD‐group. Wearing‐off: NA. On‐off fluctuations: NA. IMP: Webster: NS. DIS: no scale used.
Notes	LD:carbidopa = 10:1. Third group on BR/LD combination therapy [29]. After a mean of 16.3 months 14 patients on BR used additionally LD. Dropouts: 2 (BR), 1 (LD).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Olanow 1987

Methods	Randomised: unclear. 'Single blind'. Duration: mean 17.2 months (all patients completed first 6 months).
Participants	Country: USA. Centres: NA. Inclusion criteria: idiopathic PD and functional disability. Exclusion criteria: previous therapy of LD or dopamine agonists, Parkinson's Plus syndromes, drug‐induced parkinsonism, dementia, significant neurological or medical disease. No. Randomised: 47. Mean age: 60.6 years (BR), 63.8 years (LD). Female:Male = 8:15 (BR), 10:14 (LD). Mean disease duration: 1.3 years (BR), 1.5 years (LD).
Interventions	1) BR monotherapy (start: 1.25 mg/day, increased with 1.25 mg/week) [23]. Mean dose: 10.9 mg/day (6 months), 16.8 mg/day (15 months). 2) LD/carbidopa monotherapy (start: 50/12.5 mg/day increased with 50/12.5 mg/week) [24]. Mean dose: 322.9 mg/day (6 months), 383.3 mg/day (15 months).
Outcomes	Dyskinesias: absent. Dystonia: significant more in LD‐group at 1‐2 year(s). Wearing‐off: 1 patient in the LD‐group at 6 months. On‐off fluctuations: absent. IMP & DIS: TP score: NS.
Notes	LD:carbidopa = 4:1. After a mean of 17 months, 5 patients on BR used additionally LD. After 18 months, 1 patient on LD used additionally BR. Dropouts: 1 (BR), 4 (LD).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Riopelle 1988

Methods	Randomised: unclear. 'Double blind'. Duration: 2‐week baseline, 15‐week titration and a 6‐week maintenance phase (= pilot study, trial on going).
Participants	Country: Canada. Centres: 7. Inclusion criteria: idiopathic PD. Exclusion criteria: previously antiparkinsonism therapy other than anticholinergics. No. Randomised: 81. Mean age: 66.5 years (BR), 66.2 years (LD). Mean disease duration: NA. Female:Male = 13:29 (BR), 19:20 (LD).
Interventions	1) BR monotherapy (start: 5 mg/day increased every 3rd week to a max. of 30 mg/day [42]. Mean dose: 26.1 mg/day. 2) LD monotherapy (start: 50 mg/day increased every 3rd week to a max. of 300 mg/day [39]. Mean dose: 262.8 mg/day (plain LD).
Outcomes	Dyskinesias were absent. Dystonia: NA. Wearing‐off: NA. On‐off fluctuations: NA. IMP: CURS: NS. DIS: NUDS: NS.
Notes	LD:carbidopa = 4:1. No change in treatment regime allowed. Dropouts: 4 (BR), 0 (LD).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

UK‐PDRG 1993

Methods	Randomised: random number tables. 'Open study'. Duration: > 72 months (on going).
Participants	Country: UK. Centres: 93. Inclusion criteria: PD (according to the criteria of the PD Society of the UK Brain Tissue Bank), incapacity, which in the judgement of the clinician was sufficient to merit dopaminergic treatment. Exclusion criteria: previously failed to respond to dopaminergic drugs, incapacitating cognitive impairment. No. Randomised: 782. Selegine treatment: 271. Mean age: 62.1 years (BR), 62.7 years (LD). Female:Male = 114:148 (BR), 111:138 (LD). Mean disease duration: 14 months (1‐144).
Interventions	1) BR monotherapy (start: 2.5 mg/day increased with 2.5 mg/ 3rd day to a max. of 120 mg/d [262]. Mean dose: NA, range: 7.5 ‐120 mg/day. 2) LD/benserazide monotherapy (start: 150/37.5 mg/day increased to a max. of 300/75 mg/day [249]. Mean dose: NA, range: NA.
Outcomes	Dyskinesias: statistically significant more in LD‐group at 3 years. Dystonia: statistically significant more in LD‐group at 3 years. Wearing‐off: NA. On‐off fluctuations: statistically significant more in LD‐group at 3 years. IMP: mod. Webster statistically significant in favour of LD‐group during first year of follow up. DIS: NUDS: no results reported; the trend was similar with Webster.
Notes	LD:benserazide = 4:1. Intention to treat. No change in treatment regime. Dropouts: 181 (BR), 80 (LD).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Weiner 1993

Methods	Randomised: computerised random allocation. 'Double blind'. Duration: 4 years.
Participants	Country: USA. Centres: NA. Inclusion criteria: PD. Exclusion criteria: previously treated with BR or LD. No. Randomised: 25. Excluded patients: 1 lost to follow up (BR), 1 orthostatic hypotension (BR), 1 revised diagnosis (LD). Mean age: 60.3 years (BR), 65.7 years (LD). Female:Male = 11:14. Mean disease duration: 34 months (BR), 11.6 months (LD).
Interventions	1) BR monotherapy (start 1.25 mg/day increased to a max. of 30 mg/day [6]. Mean dose: 18 mg, range 6.25‐30 mg. 2) LD/carbidopa monotherapy (start 50/12.5 mg/d increased to a max. of 1200/300 mg/day [9]. Mean dose: 417 mg, range 150‐700.
Outcomes	Dyskinesias: significant more in LD‐group at 1‐2‐3 year(s). Dystonia: significant more in LD‐group at 1‐2‐3 year(s), only statistically significant at 3 years. Wearing‐off: NA. On‐off fluctuations: NA. IMP: mod. CURS: NS. DIS: ADL scale: significant difference in favour of BR at 1 moment (48 months).
Notes	LD:carbidopa = 4:1. No change in treatment regime. Dropouts: 1 (BR), 1 (LD).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

ADL: Activities‐of‐daily‐living (scale)
BR: bromocriptine
CURS: Columbia University Rating Scale
DIS: disability
IMP: impairment
LD: levodopa
max.: maximum
(mod.) NUDS: (modified) Northwestern University Disability Scale
(mod.) CURS: (modified) Columbia University Rating Scale
NA: not available
NS: not significant
TP: Total Parkinson's score, a combination of the modified England‐Schwab Disability Scale, a modified Columbia Scale and the Hoehn and Yahr stage with a maximum total score of 420
[X]: number of patients

Characteristics of excluded studies [ordered by study ID]

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estudios incluidos

Study	Reason for exclusion
Caraceni 2001	Bromocriptine or lisuride could be used. Results not split.
Gawel 1987	Identical to included study of Riopelle 1988.
Libman 1987	Identical to included study of Riopelle 1988.
Riopelle 1987	Identical to included study of Riopelle 1988.
Wallis 1988	Lack of final results.

Data and analyses

Open in table viewer

Comparison 1. Occurrence of dyskinesias

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 At one year Show forest plot	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.1 Comparison 1 Occurrence of dyskinesias, Outcome 1 At one year.
2 At two years Show forest plot	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.2 Comparison 1 Occurrence of dyskinesias, Outcome 2 At two years.
3 At three years Show forest plot	3		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.3 Comparison 1 Occurrence of dyskinesias, Outcome 3 At three years.
4 At four years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.4 Comparison 1 Occurrence of dyskinesias, Outcome 4 At four years.
5 At five years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.5 Comparison 1 Occurrence of dyskinesias, Outcome 5 At five years.

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Comparison 2. Occurrence of dystonia

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 At one year Show forest plot	3		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.1 Comparison 2 Occurrence of dystonia, Outcome 1 At one year.
2 At two years Show forest plot	3		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.2 Comparison 2 Occurrence of dystonia, Outcome 2 At two years.
3 At three years Show forest plot	3		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.3 Comparison 2 Occurrence of dystonia, Outcome 3 At three years.
4 At four years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.4 Comparison 2 Occurrence of dystonia, Outcome 4 At four years.
5 At five years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.5 Comparison 2 Occurrence of dystonia, Outcome 5 At five years.

Open in table viewer

Comparison 3. Occurrence of on/off‐fluctuations

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 At one year	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
2 At two years	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
3 At three years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.3 Comparison 3 Occurrence of on/off‐fluctuations, Outcome 3 At three years.
4 At four years	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
5 At five years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.5 Comparison 3 Occurrence of on/off‐fluctuations, Outcome 5 At five years.

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Comparison 4. Occurrence of wearing‐off

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 At one year Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 4.1 Comparison 4 Occurrence of wearing‐off, Outcome 1 At one year.
2 At two years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 4.2 Comparison 4 Occurrence of wearing‐off, Outcome 2 At two years.
3 At three years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 4.3 Comparison 4 Occurrence of wearing‐off, Outcome 3 At three years.
4 At four years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 4.4 Comparison 4 Occurrence of wearing‐off, Outcome 4 At four years.
5 At five years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 4.5 Comparison 4 Occurrence of wearing‐off, Outcome 5 At five years.

Open in table viewer

Comparison 5. Withdrawal rate

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All causes Show forest plot	5		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 5.1 Comparison 5 Withdrawal rate, Outcome 1 All causes.
2 Lost to follow up Show forest plot	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 5.2 Comparison 5 Withdrawal rate, Outcome 2 Lost to follow up.
3 Poor compliance Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 5.3 Comparison 5 Withdrawal rate, Outcome 3 Poor compliance.
4 Protocol violation Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 5.4 Comparison 5 Withdrawal rate, Outcome 4 Protocol violation.
5 Lack of response Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 5.5 Comparison 5 Withdrawal rate, Outcome 5 Lack of response.
6 Deterioration Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 5.6 Comparison 5 Withdrawal rate, Outcome 6 Deterioration.
7 Adverse reaction Show forest plot	4		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 5.7 Comparison 5 Withdrawal rate, Outcome 7 Adverse reaction.
7.1 Hallucinations/confusion	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 Nausea	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.3 Orthostase	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.4 Other/unclear	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Revised diagnosis Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 5.8 Comparison 5 Withdrawal rate, Outcome 8 Revised diagnosis.

Analysis 1.1

Comparison 1 Occurrence of dyskinesias, Outcome 1 At one year.

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Analysis 1.2

Comparison 1 Occurrence of dyskinesias, Outcome 2 At two years.

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Analysis 1.3

Comparison 1 Occurrence of dyskinesias, Outcome 3 At three years.

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Analysis 1.4

Comparison 1 Occurrence of dyskinesias, Outcome 4 At four years.

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Analysis 1.5

Comparison 1 Occurrence of dyskinesias, Outcome 5 At five years.

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Analysis 2.1

Comparison 2 Occurrence of dystonia, Outcome 1 At one year.

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Analysis 2.2

Comparison 2 Occurrence of dystonia, Outcome 2 At two years.

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Analysis 2.3

Comparison 2 Occurrence of dystonia, Outcome 3 At three years.

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Analysis 2.4

Comparison 2 Occurrence of dystonia, Outcome 4 At four years.

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Analysis 2.5

Comparison 2 Occurrence of dystonia, Outcome 5 At five years.

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Analysis 3.3

Comparison 3 Occurrence of on/off‐fluctuations, Outcome 3 At three years.

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Analysis 3.5

Comparison 3 Occurrence of on/off‐fluctuations, Outcome 5 At five years.

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Analysis 4.1

Comparison 4 Occurrence of wearing‐off, Outcome 1 At one year.

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Analysis 4.2

Comparison 4 Occurrence of wearing‐off, Outcome 2 At two years.

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Analysis 4.3

Comparison 4 Occurrence of wearing‐off, Outcome 3 At three years.

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Analysis 4.4

Comparison 4 Occurrence of wearing‐off, Outcome 4 At four years.

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Analysis 4.5

Comparison 4 Occurrence of wearing‐off, Outcome 5 At five years.

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Analysis 5.1

Comparison 5 Withdrawal rate, Outcome 1 All causes.

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Analysis 5.2

Comparison 5 Withdrawal rate, Outcome 2 Lost to follow up.

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Analysis 5.3

Comparison 5 Withdrawal rate, Outcome 3 Poor compliance.

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Analysis 5.4

Comparison 5 Withdrawal rate, Outcome 4 Protocol violation.

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Analysis 5.5

Comparison 5 Withdrawal rate, Outcome 5 Lack of response.

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Analysis 5.6

Comparison 5 Withdrawal rate, Outcome 6 Deterioration.

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Analysis 5.7

Comparison 5 Withdrawal rate, Outcome 7 Adverse reaction.

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Analysis 5.8

Comparison 5 Withdrawal rate, Outcome 8 Revised diagnosis.

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Comparison 1. Occurrence of dyskinesias

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 At one year Show forest plot	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

2 At two years Show forest plot	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

3 At three years Show forest plot	3		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

4 At four years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

5 At five years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

Comparison 1. Occurrence of dyskinesias

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Comparison 2. Occurrence of dystonia

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 At one year Show forest plot	3		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

2 At two years Show forest plot	3		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

3 At three years Show forest plot	3		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

4 At four years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

5 At five years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

Comparison 2. Occurrence of dystonia

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Comparison 3. Occurrence of on/off‐fluctuations

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 At one year	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
2 At two years	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
3 At three years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

4 At four years	0		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
5 At five years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

Comparison 3. Occurrence of on/off‐fluctuations

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Comparison 4. Occurrence of wearing‐off

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 At one year Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

2 At two years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

3 At three years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

4 At four years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

5 At five years Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

Comparison 4. Occurrence of wearing‐off

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Comparison 5. Withdrawal rate

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All causes Show forest plot	5		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

2 Lost to follow up Show forest plot	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

3 Poor compliance Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

4 Protocol violation Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

5 Lack of response Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

6 Deterioration Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

7 Adverse reaction Show forest plot	4		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected

7.1 Hallucinations/confusion	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 Nausea	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.3 Orthostase	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.4 Other/unclear	2		Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Revised diagnosis Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

Comparison 5. Withdrawal rate

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Referencias

Referencias de los estudios incluidos en esta revisión

Hely 1994 {published and unpublished data}

Herskovits 1988 {published data only}

Olanow 1987 {published data only}

Riopelle 1988 {published and unpublished data}

UK‐PDRG 1993 {published and unpublished data}

Weiner 1993 {published and unpublished data}

Referencias de los estudios excluidos de esta revisión

Caraceni 2001 {published data only}

Gawel 1987 {published data only}

Libman 1987 {published data only}

Riopelle 1987 {published data only}

Wallis 1988 {published data only}

Referencias adicionales

Ahlsog 1994

Begg 1996

Bernheimer 1973

Calne 1974

Canter 1961

Corrodi 1973

de Rijk 1995

Dickersin 1994

Factor 1993

Goetz 1990

Goldstein 1983

Hely 1987

Hely 1989

Hoehn 1967

Hornykiewicz 1966

Lees 1989

Lees,Frankel 1989

Luquin 1992

Marsden 1976

Marsden 1982

Parkinson's 1993

Poewe 1988

Schwab 1960

Shaw 1980

UPDRS 1987

Watts 1997

Webster 1968

Yahr 1969

Zhang 1993

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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Instituciones a las que se accedió previamente

Usuarios institucionales

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