Methods

Randomised: Yes (method used not given)

Blinding: Single (assessor)

Treatment period: Mean = 31 months

Participants

Eligibility:
Idiopathic PD patients who had not received any prior anti‐PD medication.

No. randomised
Total: 86
DA/Ctl: 26/31/29

Interventions

Comparison:
DA + LD vs. LD:
Bromocriptine
(<= 12.5 mg/d) + LD (<= 1000 mg/d) vs. LD (<= 1000 mg/d).

DA vs. LD
Bromocriptine (<= 20 mg/d) (± LD) vs. LD (<= 1000 mg/d).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose

Notes

Treatment Schedule:
Bromocriptine start 1.25 mg, increased by doses of 1.25 mg. LD start 125/12.5 mg, increased by 125/12.5 mg up to daily optimal dose.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Single (assessor)

Treatment period: 2 years

Participants

Eligibility:
Idiopathic PD patients who had never received anti‐PD medication.

No. randomised
Total: 20
DA/Ctl: 10/10

Interventions

Comparison:
Pergolide
(<= 3 mg/d) + LD
(<= 600 mg/d) vs.
LD (<= 600 mg/d)
(first 6 months ‐ DA vs. LD).

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals
Levodopa dose

Notes

Treatment Schedule:
Pergolide dose increased every 3 days (start 0.05 mg, then 0.1, 0.2, 0.25 and 0.5 mg tid), reaching 1.5 mg/d by day 15. LD dose increased every 3 days (start 25 mg, then 50, 100 mg tid), reaching 300 mg/d in 9 days. Thereafter, doses titrated individually every month. Patients on pergolide started LD after 6 months.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Double blind

Treatment period: 23 weeks

Participants

Eligibility:
Idiopathic PD patients, no previous anti‐PD therapy (other than anticholinergics).

No. randomised
Total: 81
DA/Ctl: 42/39

Interventions

Comparison:
Bromocriptine
(<= 30 mg/d) vs. LD (<= 300 mg/d) in identical capsules.

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose

Notes

Treatment Schedule:
Phase (1): 2‐week baseline. Phase (2): 15‐week titration period‐medication increased every 3 weeks until stable improvement or maximum 30 mg/d bromocriptine or 300/75 mg LD achieved.
Phase (3): 6‐week maintenance period of constant dosage.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Open

Treatment period: 5 years
(12 month data reported)

Participants

Eligibility:
Idiopathic PD patients aged < 65 years at onset of disease in Hoehn & Yahr stages I‐IV. Taken LD therapy for < 2 years.

No. randomised
Total: 277
DA/Ctl: 137/140

Interventions

Comparison:
Bromocriptine
(<= 30 mg/d) + LD (stable dose) vs. LD (stable dose).

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals
Levodopa dose

Notes

Treatment Schedule:
Bromocriptine 1.25 mg/d week 1, 2.5 mg/d week 2; thereafter, increased weekly by 1.25 mg, up to maximum 30 mg/d. LD dose stable as possible.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Double blind

Treatment period: 8 weeks

Participants

Eligibility:
Idiopathic PD patients treated with LD with basal motor status rating of at least 2 in two of the cardinal extrapyramidal symptoms using 0 to 4 UPDRS. LD dosage stable for > 1 month before start of trial.

No. randomised
Total: 36
DA/Ctl: 24/12

Interventions

Comparison:
CQA 206‐291 (<= 30 mg/d) + LD (stable dose) vs. Placebo + LD (stable dose).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals

Notes

Treatment Schedule:
CQA 206‐291 titrated within 4 weeks from 0.2 mg/d up to maximum 30 mg/d. Maintenance dose given for additional 4 weeks.
No change in LD regimen or dose allowed during study.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (computer generated list)

Blinding: Double blind

Treatment period: 3 years

Participants

Eligibility:
Aged 30 to 75 years, diagnosed < 2 years, modified Hoehn & Yahr stage 1 to 2.5, UPDRS part III score 5 to 25 and positive response to apomorphine challenge. Patients had to be LD or dopamine agonist drug naive.

No. randomised
Total: 294
DA/Ctl: 148/146

Interventions

Comparison:
Pergolide (<= 5 mg/d) vs. LD (<= 1200 mg/d).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose
Mortality

Notes

Treatment Schedule:
Study period I: 2‐week non‐randomised, non‐treatment observational period.
Study period II: 8 week fixed‐dose titration schedule, pergolide 0.05 to 0.75 mg/d and LD 50 to 150 mg/d.
Study period III: 34‐month treatment phase with flexible‐titration schedule. Maximum doses allowed 5 mg/d pergolide and 1200 mg/d LD. After 3‐years, 1‐week washout period, then 2‐weeks off medication.

Additional Treatment:
No other anti‐PD medications allowed. Rescue therapy with LD not permitted during trial.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Double blind for 1 year then open label.

Treatment period: 5 years

Participants

Eligibility:
Idiopathic PD with disease duration <= 3 years and Hoehn & Yahr stage <= 3. Patients on LD prior to study could be included if treatment duration < 1 year and daily dose < 300mg.

No. randomised
Total: 82
DA/Ctl: 41/41

Interventions

Comparison:
Lisuride
(<= 1.2 mg/d) + LD (stable dose for first year) vs. Placebo + LD (stable dose for first year)

(Placebo‐controlled for 1‐year then open dose variable study).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose

Notes

Treatment Schedule:
Adapted lisuride/placebo dose (up to maximum 1.2 mg/d) during first year without modifying initial LD dose (300 mg).
During 4 years of open trial, daily dose of LD or lisuride (in priority over LD) could be modified to obtain optimal efficacy/tolerance ratio.

Additional Treatment:
At 12 months, selegiline (10 mg/d) added to both groups. Other anti‐PD drugs prohibited during study.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (blocks of 4, stratified by country)

Blinding: Double blind

Treatment period: 6 months

Participants

Eligibility:
Idiopathic PD patients aged 35 to 75 years, PD for < 10 years (Hoehn & Yahr stage I to III). Had to be receiving LD for > 6 months but < 8 years. Prior treatment with dopamine agonist, anticholinergics and amantadine discontinued for > 1 month before screening. Patients treated with selegiline could be included as long as on stable dosage for > 1 month before entry.

No. randomised
Total: 115
DA/Ctl: 61/54

Interventions

Comparison:
Piribedil (<= 450 mg/d) + LD (4 month stable dose) vs. Placebo + LD (4 month stable dose).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose

Notes

Treatment Schedule:
Placebo run‐in period of 15 days then piribedil/matching placebo for 6 months. Titration starting dose 50 mg od, increased every 2 weeks by 50 mg up to 150 mg tid. Daily dose could be adjusted by 50 mg as necessary. Week 5 ‐ up to 6 months, patients received dosage level achieved in titration. LD kept stable until 4th month but could be adjusted afterwards.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Open

Treatment period: 4.5 years (Stopped after 4 years, due to increased mortality in LD arm)

Participants

Eligibility:
Idiopathic PD patients in Hoehn & Yahr stages I to IV, never treated with anticholinergics, amantadine or dopamine agonist and previous LD therapy < 6 months duration.

No. randomised
Total: 674 (587 analysed)
DA/Ctl: 285/302

Interventions

Comparison:
Bromocriptine (mean = 14 mg/d) + LD (60% stable dose) vs. LD (stable dose).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose
Mortality

Notes

Treatment Schedule:
Both groups: 3 month LD optimal monotherapy phase. In bromocriptine + LD group between 3 and 6 months gradual substitution of LD by up to 40 +/‐ 10% of bromocriptine. Followed by long‐term treatment phase from months 7 to 54, with dose adjusted as required.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Double blind

Treatment period: 5 years
(1 year interim analysis reported)

Participants

Eligibility:
Idiopathic PD patients established on LD (< 2 years). Anticholinergic drugs or previous treatment with amantadine were allowed, but not previous treatment with bromocriptine or selegiline.

No. randomised
Total: 31
DA/Ctl: 16/15

Interventions

Comparison:
Bromocriptine
(<= 30 mg/d) + LD (40%, <= 750 mg/d) vs. Placebo + LD (<= 750 mg/d).

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals
Levodopa dose

Notes

Treatment Schedule:
Bromocriptine/matching placebo (start 1.25 mg bid, 2.5 bid week 3, 2.5 mg tid week 5, 5 mg tid week 7, 7.5 mg tid week 9 and 10 mg tid week 10). Maximum LD dose 750 mg/d; reduced each week (week 10 LD dosage 40% of pre‐study LD).

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (computer generated blocks of 4)

Blinding: Double blind

Treatment period: 14 weeks

Participants

Eligibility:
PD for <= 3 years, modified Hoehn & Yahr stage I to III, UPDRS Motor Score > 14 points. Previous LD allowed if < 12 weeks duration. Any previous selegiline therapy discontinued > 8 weeks before entry; LD, dopamine agonists, amantadine and anticholinergics discontinued > 4 weeks before entry.

No. randomised
Total: 105
DA/Ctl: 53/52

Interventions

Comparison:
Pergolide (<= 3 mg/d) vs. Placebo.

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals

Notes

Treatment Schedule:
3‐week fixed‐dose titration period 0.05 mg/d to 0.75 mg/d. Only patients tolerating fixed‐dose titration were eligible to continue; 9‐week flexible dose period (0.75 to 3 mg/d), then fixed dose for last 2‐weeks of this period. Finally, 1 to 2‐week de‐titration period.

Additional Treatment:
No concomitant treatment with any anti‐PD agent allowed.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (computer generated list)

Blinding: Double blind

Treatment period: Until development of motor complications or maximum of 5 years treatment

Participants

Eligibility:
Newly and recently diagnosed PD patients (Hoehn & Yahr stage I to III) requiring treatment. Prior use of LD, selegiline or dopamine agonists ‐ exclusion criteria. Previous treatment with amantadine/anticholinergics allowed but had to be discontinued > 4 weeks prior to study.

No. randomised
Total: 420
DA/Ctl: 211/209

Interventions

Comparison:
Cabergoline (<= 4 mg/d) + Placebo (±LD) vs. LD (<= 600 mg/d) + Placebo (±LD).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose
Mortality

Notes

Treatment Schedule:
Cabergoline/LD titrated over 24 weeks, from 0.25 mg/d cabergoline or 100 mg/d LD to 4 mg/d cabergoline or 600 mg/d LD. Titration continued until achievement of optimal/maximum dose. Thereafter, optimal/maximum dose continued until the onset of motor complications or up to 3 years (minimum) and 5 years (maximum).

Additional Treatment:
If diminishing control open‐label LD could be added to both arms.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

Randomised: Yes (blocks, stratified by investigator)

Blinding: Double blind

Treatment period: 48 months

Participants

Eligibility:
Idiopathic PD patients aged >= 30 years, diagnosed for < 7 years with Hoehn & Yahr stage I to III, requiring dopaminergic anti‐PD therapy. Patients who had taken LD or dopaminergic agonist in 2 months prior to enrolment excluded.

No. randomised
Total: 301
DA/Ctl: 151/150

Interventions

Comparison:
Pramipexole
(<= 4.5 mg/d) + Placebo (±LD) vs. LD (<=600 mg/d) + Placebo (±LD).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose
Mortality

Notes

Treatment Schedule:
10‐week dose escalation period to 1.5 mg/d pramipexole (or matching placebo) or 300/75 mg/d LD (or matching placebo). Participants requiring additional therapy could escalate to 3 mg pramipexole or 450/112.5 mg LD, or 4.5 mg pramipexole or 600/150 mg LD.

Additional Treatment:
During maintenance open‐label carbidopa/levodopa prescribed as needed. Sustained release carbidopa/levodopa preparations not permitted.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

Randomised: Yes (method used not given)

Blinding: Double blind

Treatment period: 12 weeks

Participants

Eligibility:
Idiopathic PD patients aged 30 to 80 years (Hoehn & Yahr stages I to IV). Patients untreated or had received LD or dopamine agonists for < 6 months (discontinued > 2 weeks before screening visit).

No. randomised
Total: 63
DA/Ctl: 41/22

Interventions

Comparison:
Ropinirole (<= 10 mg/d) vs. Placebo.

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals

Notes

Treatment Schedule:
Start 0.5 mg bid, increased weekly by 0.5 or 1 mg bid to maximum dose of 5 mg bid.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (stratified by selegiline use)

Blinding: Double blind

Treatment period: 5 years

Participants

Eligibility:
PD patients in Hoehn & Yahr stage I to III who required dopaminergic therapy. Patients could have received prior LD or dopamine agonist therapy for < 6 weeks (but discontinued > 2 weeks before entry).

No. randomised
Total: 268
DA/Ctl: 179/89

Interventions

Comparison:
Ropinirole (<= 24 mg/d) + Placebo (±LD) vs. LD (<= 1200 mg/d) + Placebo (±LD).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose
Mortality

Notes

Treatment Schedule:
Ropinirole start 0.75 mg/d and LD 50 mg od plus placebo bid. Dose titration weekly intervals; maximum doses 24 mg/d ropinirole and 1200 mg/d LD.

Additional Treatment:
No other anti‐PD therapies (except rescue LD) allowed.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (within centre randomisation)

Blinding: Double blind

Treatment period: 18 months
(Stopped after 3 month interim analysis)

Participants

Eligibility:
Aged < 80 years, with untreated idiopathic PD of <= 5 years duration, Hoehn & Yahr stages I & II.

No. randomised
Total: 123
DA/Ctl: 62/61

Interventions

Comparison:
Alpha‐DHEC (<= 120 mg/d) vs. Placebo.

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals

Notes

Treatment Schedule:
Increased from 5 mg bid week 1/2, 10 mg bid week 3/4, to 20 mg bid week 5/6; then dose adjusted as necessary, up to a maximum dose of 120 mg/d.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Double blind

Treatment period: 6 months

Participants

Eligibility:
Idiopathic PD patients with stable response to LD without on‐off phenomena or dystonia/dyskinesia.

No. randomised
Total: 20
DA/Ctl: 10/10

Interventions

Comparison:
Alpha‐DHEC
(<= 60 mg/d) + LD (stable dose) vs. Placebo + LD (stable dose).

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals

Notes

Treatment Schedule:
2‐week placebo run‐in phase in addition to usual LD treatment. Then 6‐month alpha‐DHEC/matching placebo (start 3 mg/d, increased at every control without exceeding 60 mg/d).

Additional Treatment:
No dopamine agonists, anticholinergics, amantadine, selegiline or other drugs acting on CNS allowed, in addition to LD.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (blocks of 6, stratified by centre)

Blinding: Open

Treatment period:
Median = 34 months

Participants

Eligibility:
PD diagnosed < 2 years who had not taken any of the study drugs for > 4 months.

No. randomised
Total: 335
DA/Ctl: 169/166

Interventions

Comparison:
Bromocriptine
(<= 60 mg/d) or Lisuride (<= 6 mg/d) (±LD) vs. LD
(<= 750 mg/d).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Withdrawals
Mortality

Notes

Treatment Schedule:
Drug doses increased over 2‐4 weeks until optimum dose acheived. Maximum doses; 60 mg bromocriptine, 6 mg lisuride, 750 mg LD.

Additional Treatment:
If dopamine agonists were/became ineffective, LD added.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

Randomised: Yes (method used not given)

Blinding: Single (assessor)

Treatment period: Until development of motor complication or 3 years treatment

Participants

Eligibility:
Idiopathic PD patients aged 20 to 80 years in Hoehn & Yahr stages I to IV. No LD or dopaminergic agonists before study and any treatment with minor anti‐PD drugs (i.e. anticholinergic drugs) suspended > 4 weeks before entry.

No. randomised
Total: 87 (78 analysed)
DA/Ctl: 40/38

Interventions

Comparison:
Bromocriptine
(<= 15 mg/d) + LD (<= 1000 mg/d) vs. LD (<= 750 mg/d).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose

Notes

Treatment Schedule:
Bromocriptine start 1.25 mg/d at month 3, then increased every 2 weeks by same amount (maximum dose 15 mg/d). LD dose start 125 mg/d, increased each week by same amount then adjusted to achieve maximum "on" time/as little "off" time as possible.

Additional Treatment:
If diminishing clinical control, LD or bromocriptine added on an open basis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Double blind for 1st 8 months then open label.

Treatment period: 44 months

Participants

Eligibility:
Aged 40 to 70 years in Hoehn & Yahr stage <= 3 and responsive to LD therapy introduced 2 to 6 months before study entry. No previous exposure to any dopaminergic agonist allowed.

No. randomised
Total: 57 (50 analysed)
DA/Ctl: 27/23

Interventions

Comparison:
Bromocriptine
(<= 30 mg/d) + LD (75% stable dose) vs. Placebo + LD (75% stable dose).

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Withdrawals
Levodopa dose
Mortality

Notes

Treatment Schedule:
Bromocriptine 1.25 mg for 7 days, then increased by 1.25 mg weekly; after 6 weeks, increased by 2.5 mg/week, up to a maximum 15 mg by day 63. After a month, clinician attempted to reduce the LD dose by 20 to 30% (bromocriptine could be increased to maximum of 30 mg/d, with LD dose unchanged).

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Double blind

Treatment period: 5 years (Mortality at 10 years)

Participants

Eligibility:
Idiopathic de novo PD patients (including patients who had received LD for < 3 months but discontinued 1 month prior to study entry).

No. randomised
Total: 133
DA/Ctl: 66/67

Interventions

Comparison:
Bromocriptine
(<= 30 mg/d) (±LD) vs.
LD (<= 600 mg/d) in identical capsules.

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose
Mortality

Notes

Treatment Schedule:
1 month placebo baseline phase. Then 1 mg/d of bromocriptine or 20/5 mg/d LD. Dose gradually increased at weekly, then monthly intervals. Maximum doses 30 mg/d bromocriptine and 600/150 mg/d LD.

Additional Treatment:
Rescue LD could replace or be added to bromocriptine arm.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (blocks of 4)

Blinding: Open

Treatment period: 10 years (Drop‐outs at 3 years)

Participants

Eligibility:
Untreated PD patients of any age requiring dopaminergic treatment. Patients known to have failed to respond to dopaminergic drugs excluded.

No. randomised
Total: 511
DA/Ctl: 262/249

Interventions

Comparison:
Bromocriptine
(<= 120 mg/d) vs. LD.

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Withdrawals
Mortality

Notes

Treatment Schedule:
Bromocriptine start 2.5 mg, increasing by 2.5 mg every 3 days to dose of 30 mg/d. Maximum dose allowed 40 mg tid. LD start 62.5 mg tid, increased to 125 mg tid and maintained for > 3 months before further increments considered.

Additional Treatment:
Additional anti‐PD drugs allowed.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

Randomised: Yes (blocks of 4)

Blinding: Double blind

Treatment period: Until LD needed (Mean = 16 months)

Participants

Eligibility:
Aged 30 to 79 years with disease duration < 5 years, not taking nor requiring anti‐PD therapy.

No. randomised
Total: 106
DA/Ctl: 53/53

Interventions

Comparison:
Pergolide (50 µg/d) vs. Placebo.

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals

Notes

Treatment Schedule:
25 µg twice daily from week 0.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

Randomised: Yes (method used not given)

Blinding: Double blind

Treatment period: 14 months

Participants

Eligibility:
PD patients with Hoehn & Yahr stage I to III, who had >= 2 of resting tremor, bradykinesia or rigidity. Patients on no medication at baseline/received no selegiline during preceding 60 days or other anti‐PD therapy for >= 30 days prior entry.

No. randomised
Total: 101
DA/Ctl: 52/49

Interventions

Comparison:
Bromocriptine
(<= 20 mg/d) (±LD) vs. LD
(+/‐ selegiline in each arm).

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals
Levodopa dose
Mortality

Notes

Treatment Schedule:
Initiated on 10 mg/d of selegiline or matching placebo. On 3rd day started either bromocriptine (5 mg) or LD (25/100). Dose of bromocriptine titrated up or down as appropriate.

Additional Treatment:
Bromocriptine patients could receive supplementary LD once 20 mg/d bromocriptine achieved.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (computer generated blocks of 10, stratified by investigator)

Blinding: Double blind

Treatment period: 11 weeks

Participants

Eligibility:
Aged > 30 years with idiopathic PD for < 7 years; Hoehn & Yahr stages I to III. Did not require anti‐PD treatment and had not taken such medication within 3 months prior to enrolment.

No. randomised
Total: 264
DA/Ctl: 213/51

Interventions

Comparison:
Pramipexole (1.5, 3, 4.5 or 6 mg/d) vs. Placebo.

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals
Mortality

Notes

Treatment Schedule:
Titration schedule used (including up to 4 weeks of matching placebo); target/achieved dose (1.5, 3, 4.5 or 6 mg/d) by week 6 for 4 weeks, then 1‐week discontinuation period.

Additional Treatment:
LD or other dopamine agonists not permitted during study. Selegiline, anticholinergics and amantadine permitted if stable dosages for 30 days prior to and during study.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

Randomised: Yes (method used not given)

Blinding: Double blind

Treatment period: 4 years (Mean = 40 months)

Participants

Eligibility:
PD patients previously untreated with bromocriptine or LD.

No. randomised
Total: 25
DA/Ctl: 7/8/10

Interventions

Comparison:
DA + LD vs. Placebo + LD:
Bromocriptine (<= 18 mg/d) + LD
(<= 1200 mg/d) vs. Placebo + LD (<= 1200 mg/d).

DA + LD:
Bromocriptine (<= 30 mg/d) + Placebo vs. LD (<= 1200 mg/d) + Placebo.

Outcomes

Data Reported:
Clinician rated disability
Motor complications
Side‐effects
Withdrawals
Levodopa dose

Notes

Treatment Schedule:
Bromocriptine start 2.5 mg/d, then after 2 weeks LD (100/25 mg) added. Doses could be gradually increased to maximum doses of 18 mg bromocriptine and 1200/300 mg LD.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (method used not given)

Blinding: Double blind

Treatment period: 9 weeks

Participants

Eligibility:
Aged > 20 years with early idiopathic PD (Hoehn & Yahr stages I to III).

No. randomised
Total: 56
DA/Ctl: 28/28

Interventions

Comparison:
Pramipexole (<= 4.5 mg/d) vs. Placebo.

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals

Notes

Treatment Schedule:
Start 0.3 mg/d, increased weekly up to 4.5 mg/d by week 6, then 3‐week fixed maintenance dose phase, then dose reduction phase.

Additional Treatment:
Selegiline (10 mg/d) received throughout. No other anti‐PD medications allowed.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (stratified by selegiline and centre)

Blinding: Double blind

Treatment period: 8 months

Participants

Eligibility:
Aged > 25 years with idiopathic PD in Hoehn & Yahr stage I to III, not taking LD. Up to 180 days of prior LD exposure allowed, but LD‐free for 60 days prior to entry.

No. randomised
Total: 335
DA/Ctl: 165/171

Interventions

Comparison:
Pramipexole (<= 4.5 mg/d) vs. Placebo.

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals

Notes

Treatment Schedule:
Dose titration over 7‐week period, 0.375 to 4.5 mg/d. Then 6 month maintenance phase (on maximum dose), then 1‐week dose‐reduction phase.

Additional Treatment:
Selegiline allowed if dose stable for 30 days and did not exceed 10 mg/d.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Randomised: Yes (stratified by selegiline use)

Blinding: Double blind

Treatment period: 6 months

Participants

Eligibility:
Early PD (Hoehn & Yahr stages I to III) requiring dopaminergic therapy, but no LD or any dopaminergic agonist for > 6 weeks prior study entry. All anti‐PD therapies, except selegiline, discontinued > 4 weeks prior to entry.

No. randomised
Total: 241
DA/Ctl: 116/125

Interventions

Comparison:
Ropinirole (<= 24 mg/d) (±LD) vs. Placebo (±LD).

Outcomes

Data Reported:
Clinician rated disability
Side‐effects
Withdrawals

Notes

Treatment Schedule:
Start 0.25 mg tid, then titration up to optimal response (minimum 1.5 mg tid, maximum 8 mg tid) for remainder of study.

Additional Treatment:
Patients on selegiline remained on stable dose for 4 weeks prior to entry and during study. Additional therapy (LD) permitted if patient first been titrated to highest tolerated.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear