Objective

Background

Gabapentin (Neurontin) has recently been recognized to be successful in the treatment on restless legs syndrome. Gabapentin is an anitconvulsant with known effectiveness as adjunctive therepy in the treatment of partial seizures with and without secondary generalization in adults with epilepsy. First introduced in February 1994, gabapentin, a structural analogue of GABA, was synthesized as a GABA-mimetic drug which could cross the blood-brain barrier, however, its pharmacodynamic mechanism is different from other substances that interct with GABA synapses, such as valproic acid, phenobarbital, benzodiazepines, and vigabatrin. Its binding occurs in the outer layers of the neocortex, hippocampus, and other brain locations but the receptor and its biochemical function remain undiscovered. Pharmacologic studies disclose that gabpentin does not bind to benzodiazepine, glutamate, glycine, GABAa, GABAb, and NMDA receptors and may have a novel binding site in the nervous system.

Results

Conclusion

The mechanism of gabapentin induced RLS relief is unknown; however, animal research by Xiao and Bennett has recently shown that gabapentin provides significant efficancy against heat-hyperalgesia and mecho-allodynia in rats and that this pain relief appears to be meditated largely or entirely by a spinal site of action.

Other research has shown a gabapentin induced elevation of CNS serotonin (5HT) in both humans and animals. A 5HT mechanism may occur via the raphe-spinal descending control system which acts to impede nociception at the substantia gelatinosa of the spinal cord, an area with high density of projections from the raphe magnus and which contains substance P terminals, opiate reeptors, and serotonin terminals.

Satisfactory relief of symptoms of restless leg syndrome in these patients suggests that gabapentin (Neurontin) may be effective new therapy for this condition. We believe the role of gabapentin in the treatment of restless legs syndrome-periodic limb movement disorder merits further scientific investigation. This report represents the first documented use of gabapentin for restless legs syndrome.

Drs. Gary and Larry Mellick have prescribed this drug to 16 patients with RLS at a dosage range of 300 to 2,000 mg per day. Patients ranging from 36 to 75 years of age with RLS for one to forty years experienced 50-100% control of their RLS dyesthesias and associated leg movements after beginning gabapentin. Relatively few adverse effects have been experienced by these patients and relief of their symptoms have been sustained.

A number of patients report relief of periodic limb movement disorder and all patients describe improved qulality of sleep with few nocturnal awakenings. All patients have achieved satisfactory control without experiencing the symptom rebound frequently associated with dopaminergic therapy.

There's been much talk in the RLS/PLMS community about the drug Neurontin, and David has described his experiences with the drug to the Cyberspace support group. I've been on Neurontin for just over a week, and I thought this would be a good time to report on my experiences with the drug to the group, because my symptoms differ significantly both in quality and severity from David's, and because of the interest that I believe we all have in Neurontin.

By way of background, I'm 43, and I have PLMS but no RLS. This means I have sleep difficulties, but I have no paresthesia in my legs or other limbs. Since there's no paresthesia, I have no trouble whatsoever falling asleep, but I awaken anywhere from five to seven hours later, unable to return to sleep, but feeling quite tired. I've had PLMS for nine years, but the problem was first diagnosed as depression, and it was not correctly diagnosed until a sleep lab study was done in early 1994. That study showed that while the quantity of sleep was poor, the quality of sleep was far worse: the periodic limb movements during sleep so badly disrupted my sleep cycle, that I was getting mimimal REM sleep.

Before trying Neurontin, I tried Klonipin and Sinemet. Klonipin produced only a slight improvement in the restfulness of my sleep, but no change at all in sleep duration. Sinemet did nothing for me but give me a dry mouth.

I've been on Neurontin for nine days now. The dosage has been two 300mg capsules at bedtime. The main effect of Neurontin has been a significant improvement in the restfulness of my sleep. I still feel tired during the day, but less so than previously. While there have been no serious side effects to the drug, I've noticed some grogginess upon awakening, but this seems to be gradually fading. The Neurontin has had less effect on the quantity of sleep. I still get about six hours of sleep, although on the third or fourth day, I slept for nine hours. During the last three days, sleep duration has shown very slight improvement, but given that my symptoms (and it seems the symptoms of most RLS/PLMS sufferers) can fluctuate significantly from day to day, it's too soon to say if this slight improvement is significant.

Apart from the improvements in sleep restfulness, I'm noticing two improvements (other than sleep itself) that may be byproducts of better sleep. First, my appetite has increased noticeably since I started on Neurontin. To the best of my knowledge, Neurontin is not an appetite stimulant, but ever since my PLMS started, my appetite has been a bit depressed. Three days ago, I had three complete meals: breakfast, lunch and dinner. I can't remember the last time that happened. Also, I seem to be handling stress much better.

My physician said I could increase my dosage beyond 600mg if that was necessary to obtain adequate relief. I haven't told him yet about my experiences with Neurontin, but I plan to do that tomorrow, and I'll ask him then if I should increase the dosage.

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