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L-dopa for RLS

Clinical bottom line

Only 142 patients have been enrolled in RCTs of L-dopa. Most of the studies were small, and concentrated on sleep parameters. L-dopa does appear to reduce periodic limb movements, but there is no clear picture of reduced symptoms of RLS.


Reference

PW Kaplan et al. A double blind placebo controlled study of the treatment of periodic limb movements in sleep using carbidopa/levodopa and propoxyphene. Sleep 1993 16: 717-723.

C Trenkwalder et al. L-dopa therapy of uraemic and idiopathic restless legs syndrome: a double-blind crossover trial. Sleep 1995 18: 681-688.

J Staedt et al. Pergolide: treatment of choice in restless legs syndrome (RLS) and nocturnal myoclonus syndrome (NMS). A double-blind randomized crossover trial of pergolide versus L-Dopa. Journal of Neural Transmission 1997 104: 461-468.

H Benes et al. Rapid onset of action of levodopa in restless legs syndrome: a double-blind randomized multicenter crossover trial. Sleep 1999 22: 1073-1081.

V Collado-Seidel et al. A controlled study of additional sr-L-dopa in L-dopa-responsive restless legs syndrome with late night symptoms. Neurology 1999 52: 285-290.

M Saletu et al. Acute double-blind placebo controlled sleep laboratory and clinical follow up studies with a combination treatment of rr-L-dopa and sr-L-dopa in restless legs syndrome. Journal of Neural Transmission 2003 110: 611-626.

Clinical trials

There were six trials (Table 1). Most were involved with sleep studies, and some were very short term. All were small. None reported outcomes in terms of patients with RLS resolved completely or partially.

Results

In total 142 patients received L-dopa in one form or another. There was a consistent picture of reduction in periodic limb movements while asleep, but no consistent picture of resolution of RLS symptoms. Treatment-related adverse events were usually mild.

Table 1: Clinical trials with L-dopa

Reference
Design
Treatments and Outcomes
Patient details
Efficacy
Adverse Events
Kaplan et al. Sleep 1993 16: 717-723 R = 1
DB = 1
WD = 0
QS = 2
Crossover
Duration = three periods of two weeks
Treatments
1 Carbidopa/levodopa (25/100 mg; 50/200 mg)
2 Propoxyphene 100 mg and 200 mg daily (6)
3 Placebo (6)

Outcomes
Sleep studies, leg activity
Average age 61 years (range 44-72), 4 women/2 men Dopa provided some significant improvements in sleep. Dopa, but not propoxyphene, significantly reduced the number of periodic leg movements Few minor adverse events reported. One discontinuation on propoxyphene
Trenkwalder et al. Sleep 1995 18: 681-688 R = 1
DB = 1
WD = 1
QS = 3
Crossover
Duration = two periods of four weeks
Treatments
1 L-dopa 100 mg plus benserazide 25 mg (32) at night
2 Placebo (32)

Outcomes
Sleep measurements, rating of symptoms and quality of life
Average age 52 years (range 29 to 73 years), 17 with idiopathic and 11 uraemic RLS on dialysis L-dopa was significantly better than placebo on many sleep outcomes. Significant reduction in periodic leg movements over placebo with L-dopa. Significant improvement in RLS symptoms at night, and quality of life, with L-dopa Adverse events were reported by
12/32 L-dopa
8/32 placebo
One severe adverse event on L-dopa
Two uraemic patients discontinued
Staedt et al. J Neural Transm 1997 104: 461-468 R = 1
DB = 2
WD = 1
QS = 4
Crossover
Duration = two 16-day phases
Treatments
1 Pergolide 0.125 mg daily (11)
2 250 mg L-dopa + carbidopa (11)

Outcomes
Sleep studies and symptoms
Eleven patients aged 50-69 years, with duration of RLS 2-15 years, half female Therapeutic response of complete relief of night time restlessness
9/11 pergolide
1/11 dopa
No significant change in sleep
There were no serious adverse events
Nausea 9/11 pergolide
1/11 dopa
Benes et al. Sleep 1999 22: 1073-1081 R = 2
DB = 2
WD = 1
QS = 5
Crossover
Duration = two four week treatment periods
Treatments
1 L-dopa 100 mg plus benserazide 25 mg (35) at night
2 Placebo (35)

Outcomes
Leg movements while asleep, RLS and sleep quality, and quality of life
Average age 56 years (range 30 to 70 years), mean duration of RLS about 20 year, 60% women L-dopa produced significant improvements in leg movements while asleep by more than 50%, and in physician rating of sleep, RLS symptoms, and quality of life Patients with drug-related AE:
7/32 L-dopa
8/32 placebo
AE discontinuation:
0/32 L-dopa
2/32 placebo
Collado-Seidel et al. Neurology 1999 52 285-290 R = 1
DB = 1
WD = 1
QS = 3
Crossover
Duration = two four week periods
Treatments
1 sustained release-L-dopa 100 mg plus benserazide 25 mg (37) at night
2 Placebo (37)
both given to patients stabilised on regular release L-dopa 100 mg

Outcomes
RLS symptoms and sleep quality, and quality of life
Average age 58 years (range 31 to 75), two thirds women, mean duration of RLS 20 years, 3 with uraemic RLS Sustained release L-dopa significantly better than placebo on most measures, but not physician rating of RLS symptoms Three patients discontinued treatment, two because of serious adverse events
Saletu et al. J Neural Transm 2003 110:611-626 R = 1
DB = 1
WD = 1
QS = 3
Crossover
Duration = about 7 days
Treatments
1 100 mg regular release and 100 mg sustained release L-dopa plus bensarazide at night (21)
2 Placebo (21)

Outcomes
Mainly sleep studies
No patient data L-dopa reduced the number of period limb movements asleep and other RLS variables, but failed to improve sleep efficacy or quality No adverse events on placebo. Mild adverse events on l-dopa

 

Comment

This is not sufficient information on which to base treatment judgements.