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RLS treatments compared

Clinical bottom line

There is little clinical trial information on drugs for RLS. Nine drugs have been tested in only a single trial, and for only two drugs have been tested on more than 100 patients, L-Dopa (142) and ropinirole (233). The best information in terms of overall results and numbers exists for ropinirole and pergolide, though there are restrictions in some countries about prescribing pergolide.


Trials in RLS (March 2005)

Trials in RLS are characterised as being relatively small and relatively short duration, predominantly of 2-4 weeks. Only some trials with ropinirole have had durations up to 12 weeks. Most have relatively good reporting quality, and have been adequately randomised and blinded.

Outcomes measured are of several general types:

  1. Sleep outcomes: these can be detailed and are obtained in relatively small numbers of patients in sleep laboratories. These can include sleep latency (time to fall asleep), sleep duration, and more complicated aspects of sleep.
  2. Periodic leg movements while asleep: again obtained from sleep laboratory studies.
  3. RLS symptoms: there are internationally recognised symptom sets, and that usually used is from the International Restless Legs Syndrome Study Group (IRLSSG).

Results

The amount of information is shown in Table 1. Ropinirole and L-Dopa were studied in six trials, but the larger data set, longer trials, and better results were seen with ropinirole. Results with pergolide were also quite good, though only 84 patients were given the drug. Pergolide use in patients with Parkinson's syndrome may be restricted because of the occurrence of sudden sleep episodes that may cause accidents.

Other drugs were used in small single trials or several small trials, with insufficient information from which to draw any satisfactory conclusions.

Table 1: Summary of trials in RLS

Number of
Drug
Trials
Patients on drug
Main results
Some evidence
Ropinirole
6
233
Ropinirole was significantly better than placebo or L-dopa in producing good results in patients with much or very much improved results on global impression of treatment, or patients with no RLS symptoms. 169/310 patients (55%) had the outcome with ropinirole compared with 109/304 (36%) with placebo or L-dopa. Most patients were in longer duration trials
L-Dopa
6
142
Consistent picture of reduction in periodic limb movements while asleep, but no consistent picture of resolution of RLS symptoms.
Pergolide
4
86
73/96 patients on pergolide (76%) had an outcome of almost or complete abolition of RLS symptoms, compared with 18/102 (18%) on placebo or L-Dopa
Carbamazepine
1
84
On the basis of this single trial, carbamazepine appears to have some efficacy, at least over the short term
Gabapentin
3
48
On the basis of very limited information from 48 patients, gabapentin appears to be effective for treatment of RLS
Iron
2
25
Possibly some effect in people with anaemia
Too little evidence in patient number or effect
Carbergoline
1
63
 
Rotigotine
1
49
 
Hydroquinine
1
48
 
Oxycodone
1
11
 
Clonidine
1
10
 
Pramipexole
1
10
 
Clonazepam
1
6
 
Bromocriptine
1
6
 

Comment

Where there was sufficient evidence, some treatments were obviously effective, ropinirole and pergolide, for instance, while others, like L-Dopa, were less effective. Ant comparisons must be tempered by the relative paucity of evidence for most treatments.

Outcomes most affected were periodic limb movements while asleep, and sleep latency. Symptoms were often less affected, though some trials report a significant proportion of treated patients with a large reduction of even elimination of RLS symptoms. This is interesting, because all of the trials have used patients with moderate or severe RLS symptoms, and who have generally had RLS symptoms for many years, often decades.

One final comment about results with placebo. In general, short term trials have little in the way of any effect seen with placebo. Some of the longer-term 12-week studies with ropinirole demonstrate much greater effects with placebo with longer duration. This probably is a description of periodicity in RLS symptoms. Any such periodicity has two possible consequences, first that comparing different treatments at different times would be wrong, and more important, that treatments for RLS might not need to be continuous. The literature is relatively silent on both topics.