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To synthesize evidence from available randomized controlled trials (RCT) to compare the efficacies of dopaminergic drugs (pramipexole, ropinirole and rotigotine) and α-2-δ ligands (gabapentin enacarbil and pregabalin) for the treatment of restless legs syndrome (RLS). Restless legs syndrome (RLS) refers to an urge to move the legs, usually associated with unpleasant sensations. The urge to move the legs is worse at rest and at night and is relieved by movement. RLS is commonly associated with sleep disturbance and with involuntary, jerking movements of the legs during sleep, known as periodic limb movements Use of Alpha-2-Delta Ligand Calcium Channel Blockers: New evidence supports the strong recommendation for the use of three alpha-2-delta ligand calcium channel blockers — gabapentin enacarbil, gabapentin, and pregabalin — for the treatment of RLS. These medications are not associated with the augmentation of RLS symptoms. Pregabalin has been shown to be an effective monotherapy for managing RLS symptoms when compared to placebo or active treatment with a DA (6, 8 – 10). However, there have been no studies using pregabalin as an add-on agent with DA. Gabapentin and pregabalin also attenuate RLS symptoms, and gabapentin enacarbil (a long-acting form of gabapentin) is FDA-approved for RLS. In this trial, researchers randomized 719 patients with moderate-to-severe RLS to receive pregabalin (300 mg daily), pramipexole (0.25 mg or 0.5 mg daily), or placebo. Gabapentin and pregabalin are FDA-approved to treat some of the same conditions, including postherpetic neuralgia in adults. Both drugs are also indicated to treat partial seizures in adults and certain children with epilepsy (a seizure disorder) when taken along with other medication. Pregabalin (Lyrica) and gabapentin (Neurontin) are both approved to treat nerve pain. How are they different, and which one is preferred? Compare both meds here. For subjective sleep measures, clinicians should consider prescribing cabergoline or gabapentin enacarbil (Level A), or ropinirole, pramipexole, rotigotine, or pregabalin (Level B). For patients failing other treatments for RLS symptoms, clinicians may consider prescribing prolonged-release oxycodone/naloxone where available (Level C). Medicines Doses as per NICE CKS Restless legs syndrome guidance Pregabalin The use of pregabalin for restless legs syndrome (RLS) is off-label. Initial dose: 75 mg in people aged under 65 years and 50 mg in people aged over 65 years. Titration: maximum recommended daily dose for RLS is 450 mg. CKS did not identify any specific guidance on There are three gabapentinoids on the market: gabapentin, gabapentin enacarbil, and pregabalin. These drugs are considered first-line therapy for RLS. Gabapentin enacarbil and pregabalin tend to be absorbed better and more reliably effective than gabapentin due to variability in how gabapentin is absorbed in the intestines. In contrast, new evidence supporting three alpha-2-delta ligand calcium channel blockers — gabapentin enacarbil, gabapentin, and pregabalin — led the task force to support them as strong recommendations for RLS treatment. These medications are not associated with the augmentation of RLS symptoms observed with the dopaminergic agents. Medicines such as gabapentin, gabapentin enacarbil and pregabalin are the first line of treatment for most people with RLS. These medicines can cause side effects such as dizziness, unsteadiness, mental fog and weight gain. Medicines that increase dopamine in the brain. These medicines affect levels of the chemical messenger dopamine in the brain. Keywords: restless legs syndrome, gabapentin, gabapentin enacarbil, treatment. Background. Restless legs syndrome (RLS) is a movement disorder that affects between 5% and 10% of adults [Hening et al. 2004; Phillips et al. 2000; Lavigne and Montplaisir, 1994]. Gabapentin is a prescription drug sold under the brand name Neurontin, Horizant, and others that is used to treat symptoms of restless legs syndrome (RLS) as well as partial seizures and postherpetic neuralgia. In moderate to severe primary restless legs syndrome (RLS), clinicians should consider prescribing a pharmacologic agent to reduce RLS symptoms: Strong Evidence Pramipexole, rotigotine, cabergoline*, and gabapentin enacarbil ( Level A ). Dopaminergic medications relieve symptoms of the restless legs syndrome (RLS) but have the potential to cause iatrogenic worsening (augmentation) of RLS with long-term treatment. Pregabalin may be Restless legs syndrome (RLS) is a common disorder. The population prevalence is 1.5% to 2.7% in a subgroup of patients having more severe RLS with symptoms occurring 2 or more times a week and causing at least moderate distress. It is important for primary care physicians to be familiar with the disorder and its management. Gabapentin enacarbil is a prodrug of gabapentin, converted to gabapentin after absorption, and thus avoids the nonlinear pharmacokinetics of gabapentin. It is administered as a single daily dose of 600 mg (300 mg in patients older than 65 years) at 5 pm to target adequate therapeutic levels at bedtime. Published concerns about dopaminergic augmentation of RLS symptoms from levodopa date back to the mid-1990s. 29 Heightened awareness of augmentation with long-term dopamine agonist use emerged in the early 2000s as their clinical use became widespread. 29 – 33 Furthermore, the occurrence of impulse control disorders in patients with RLS
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