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Gabapentin for restless legs (RLS): What you need to know

Currently, gabapentin remains the first line of treatment for moderate restless legs syndrome
Mariquissa Beverly, DPM
By | Jun. 13, 2024
A woman holding the lower level of her leg: Gabapentin for restless legs

Key takeaways

  • Although gabapentin is traditionally prescribed for seizure management and postherpetic neuralgia, it is also used off-label for restless legs syndrome (RLS) and many other nerve conditions.

  • Gabapentin enacarbil is one of four medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of RLS.

  • Gabapentin helps improve the nerve signals to the muscles of the legs that contribute to the cause of RLS. 

  • The preferred dose for management of RLS with gabapentin enacarbil is 600 mg/daily, but higher doses may be needed for some individuals.

In this article:

If you are among many Americans who have trouble sleeping due to the uncontrollable urge to move your legs in the evening or while resting, you are likely familiar with the term restless legs syndrome (RLS). 

Your healthcare provider may have already diagnosed you with this condition and reviewed some available treatment options. The cause of restless legs syndrome is still unknown, but there has been some consensus that an imbalance of dopamine in the brain may contribute to the cause. No set diagnostic tests are available to diagnose this condition. Therefore, your healthcare provider needs to take a thorough history and perform a physical exam to make an accurate diagnosis. 

Some risk factors or medical conditions are associated with developing restless legs syndrome. These include pregnancy or any conditions that cause hormonal changes, kidney problems, peripheral neuropathy, vitamin deficiencies, vascular disease, back injuries, sleeping disorders, and Parkinson’s disease. The use of alcohol, caffeine, and nicotine is also linked to restless legs syndrome. 

Although there is no cure for severe primary RLS, there is medical help available to improve symptoms associated with this nerve disorder. 

Does gabapentin help with restless leg syndrome (RLS)?

Yes. Gabapentin enacarbil is a type of anticonvulsant approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe primary RLS. It is known as a prodrug of gabapentin. The difference between gabapentin and gabapentin enacarbil is that gabapentin enacarbil is taken once daily, whereas gabapentin can be taken up to three times a day. 

Gabapentin was initially developed for seizures and postherpetic neuralgia but has become a popular option for the management of symptoms associated with moderate to severe primary RLS with the prodrug option. How gabapentin works to improve nerve pain is still unknown. It is believed to target calcium channels in the brain, normalizing neurotransmitters. This then enhances the nerve signals in the legs, not the muscles.

Typically, gabapentin is started at a very low dose and gradually increased to reach maximum effectiveness without symptoms. Since each person is different, different doses and frequencies may be needed individually to improve primary RLS. Therefore, it may take some time to find the optimal dose. However, once the appropriate dose has been found, typically, relief of symptoms can be seen in about 4 weeks after initiation of gabapentin. Because restless legs symptoms are usually more pronounced in the evening, gabapentin is generally recommended during this time. One of the most common side effects of use of gabapentin is drowsiness. Therefore, the medication is also better tolerated when taken in the evening.

Gabapentin dosage for restless legs

When you and your medical doctor decide to use medications, the safety of gabapentin enacarbil will be discussed. To reduce the serious side effects of gabapentin, usually a very low dose is initiated. The minimum dose started while treating restless legs syndrome is 300 mg once daily. Patients typically report minimal to no improvement of symptoms at this dose. Still, a slower approach to prescribing this medication may be taken to ensure there are no serious adverse effects of gabapentin enacarbil. 

The best results are seen with the recommended standard dose of 600 mg once daily. The maximum daily dosage of gabapentin enacarbil is 1800 mg. Higher doses than this may lead to less tolerability of gabapentin enacarbil. Caution should be taken if higher doses are needed for symptom relief. 

Gabapentin is taken long-term and should be reevaluated by your physician every three months. If the symptoms of restless legs syndrome are mild or infrequent, as-needed options such as benzodiazepines, muscle relaxants, or opioids may be more appropriate. If symptoms are not improving with the initial dose, communication with your physician is key, as they will be able to adjust the dose to provide more symptom relief.

Side effects and interactions of gabapentin

Here are a few potential side effects of gabapentin:

More serious adverse effects include suicidal thoughts, depression, and serious breathing problems. Be aware of these serious side effects and seek medical help with your MD if any serious adverse effects occur. Your gabapentin may need to be discontinued or at least reduced to prevent allergic reactions. 

There are also some known medication interactions while taking gabapentin, including:

  • Narcotics
  • Antacids
  • CNS depressants
    • Benzodiazepines: Xanax (alprazolam), Ativan (lorazepam), Klonopin (clonazepam)
    • Antihistamines: Benadryl (diphenhydramine), Vistaril (hydroxyzine)
    • Sedatives: Ambien (zolpidem), Lunesta (eszopiclone)
    • Muscle relaxants: Flexeril (cyclobenzaprine), baclofen

RELATED: Can you take gabapentin with Flexeril?

Mixing gabapentin with alcohol, cannabis, caffeine, and some supplements should also be avoided due to potential allergic reactions. Being transparent with your healthcare provider on your habits can help them determine if gabapentin will be the best treatment of choice for your moderate RLS symptoms. The addition of new medicine without prior knowledge of your doctor can place patients at risk for unwanted adverse events.

Other RLS treatments

If gabapentin is not the right choice for you, there are many alternative treatments available. Typically, other treatment options for moderate to severe Primary RLS may include something simple, such as lifestyle modifications and supplements or other medications (muscle relaxers, sleeping aids, narcotics, or other anticonvulsants).

Lifestyle modifications

Lifestyle modifications are effective in mild cases of RLS and can help reduce symptoms in more moderate to severe cases. Other lifestyle modifications include:

  • Reducing alcohol and caffeine intake
  • Better sleep habits
  • Exercise 
  • Mental stimulation (i.e., crossword puzzles)
  • Avoiding medications that trigger symptoms (antihistamines, antidepressants, antipsychotics, and thyroid medications)
  • Consuming a well-balanced diet

Supplements

Supplements may help with vitamin deficiencies that contribute to RLS symptoms. These include: 

  • Iron 
  • Vitamin D
  • Vitamin C
  • Vitamin E

Muscle relaxants

Muscle relaxants can help with RLS by reducing muscle tension and providing relief from muscle discomfort and spasms. Common muscle relaxants used in the treatment of RLS include:

Sedatives

Sedatives can help with restless legs syndrome (RLS) by promoting relaxation and improving sleep quality, including:

Benzodiazepines

Benzodiazepines are central nervous system depressants that can help relax muscles and calm the nervous system, potentially reducing the discomfort associated with RLS. Some examples include:

Dopaminergic agents

Dopaminergic agents help with restless legs syndrome (RLS) by increasing the level of dopamine in the brain. These include:

Other anticonvulsants

Anticonvulsants like gabapentin help with RLS by stabilizing electrical activity in the brain and nervous system. Lyrica (pregabalin) binds to calcium channels in the central nervous system, which helps to decrease the release of neurotransmitters involved in pain signaling.

Narcotics

Narcotics are typically reserved for cases that do not respond to other treatments due to the potential for dependence and other side effects. Some examples include: 

Many patients are interested in knowing which medication has the fewest side effects and can help them quickly relieve their symptoms. Because every person’s pain level and tolerance differ, there is no way to know what will work best for you and how quickly. Currently, gabapentin remains the first line of treatment for moderate restless legs syndrome. 

Which is better for restless legs, ropinirole or gabapentin?

Other popular treatments, such as dopaminergic agents (ropinirole), exacerbate restless legs syndrome. This means the symptoms can progressively get worse over time while taking this medication. For those with chronic or more severe cases, combination therapy of multiple treatment modalities may be used to provide relief of their symptoms. 

Is there any immediate relief for restless leg syndrome?

Unfortunately, there is no medical cure for restless legs syndrome. However, some home remedies and medications may provide immediate relief from mild to moderate symptoms. Here are some alternative treatment options that may be beneficial while managing restless leg syndrome:

  • Warm bath
  • Ice pack
  • Heating pad
  • Reduce stress
  • Massage
  • Exercise (yoga, walking, stretches)
  • Transcutaneous electrical nerve stimulation (TENs unit)
  • Acupuncture

Some over-the-counter (OTC) options that may be readily available and improve symptoms quickly include:

  • Aspercreme
  • Capzasin 
  • Ibuprofen
  • IcyHot
  • Salonpas

Gabapentin remains the standard treatment for moderate—to severe primary RLS in clinical practice. Luckily, several treatment options are available that may improve those intense urges to move during the night, which ultimately impact your sleep and rest cycle. Some people may even opt for an addition of another treatment, especially if gabapentin is not fully effective. Whatever decision is made to manage your restless legs syndrome symptoms, SingleCare is always here to help reduce costs with our prescription savings card.

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