Clinical Question: Does gabapentin (Neurontin) improve symptoms in patients with restless leg syndrome (RLS)?

Setting: Outpatient (specialty)

Study Design: Cross-over trial (randomized)

Synopsis: This study focuses on the effect of gabapentin on patients with RLS. The investigators enrolled eight men and 16 women with RLS who had not been treated previously with gabapentin or a dopaminergic agent (e.g., bromocriptine, levodopa). The patients had moderate RLS based on the RLS Rating Scale (average score: 20 out of a possible 40 points, 40 being the worst). Oddly, the report provides almost no other information about the baseline status of the patients, such as the range of baseline scores on the RLS Rating Scale. This information is important, given that the investigators found better results in patients with higher than average scores at baseline.

The patients received, in a randomized fashion, gabapentin or placebo for six weeks. The dosage of 600 mg daily could be changed every two weeks to a maximum of 2,400 mg per day. After one week of no therapy, the study participants were switched to the alternative treatment. Allocation and treatment assignment were carefully hidden from the investigators, although the patients may not have been masked to treatment. Forty-eight percent of patients taking gabapentin experienced side effects compared with only 21 percent of patients taking the placebo. Because all of the rating scales involved patient self-assessment, the presence of side effects could have led the subjects to think the medication was “working,” resulting in higher scores.

After six weeks of therapy, scores on the RLS scale were significantly different while patients were taking gabapentin (9.5 versus 17.9 for placebo, P <.0005). Patients' global impressions of change were also different at the end of therapy (8.3 cm on a 10-cm visual analog scale versus 6.3 cm with placebo, P <.001). The researchers did not note whether this difference was clinically important. Similarly, while patients took gabapentin, improvements were seen on the Pittsburgh Sleep Quality Index and on some measures of sleep architecture but not others. Pain scores were low at the beginning of the study (2.2 cm on a 10-cm visual analog scale) and were not affected by active treatment.

Bottom Line: Gabapentin, in dosages of about 1,800 mg per day, was more effective than placebo in diminishing some symptoms of RLS. Side effects, although not major, occurred in about one half of patients and could have led them to think the medication worked better than it actually did. (Level of Evidence: 1c)