Gabapentin is Used to Treat Restless Legs Syndrome

Gabapentin (Neurontin) is FDA approved to treat epilepsy and a type of nerve pain caused by shingles (postherpetic neuralgia).

Restless legs syndrome (RLS) is a disorder of the part of the nervous system that causes an urge to move the legs. Because it usually interferes with sleep, it also is considered a sleep disorder.

 

Causes of Restless Legs Syndrome

In most cases, doctors do not know the cause of restless legs syndrome; however, they suspect that genes play a role. Nearly half of people with RLS also have a family member with the condition.

Other factors associated with the development or worsening of restless legs syndrome include:

  • Chronic diseases. Certain chronic diseases and medical conditions, including iron deficiency, Parkinson’s disease, kidney failure,diabetes, and peripheral neuropathy often include symptoms of RLS. Treating these conditions often gives some relief from RLS symptoms.
  • Medications. Some types of medications, including antinausea drugs, antipsychotic drugs, some antidepressants, and cold and allergymedications containing sedating antihistamines, may worsen symptoms.
  • Pregnancy. Some women experience RLS during pregnancy, especially in the last trimester. Symptoms usually go away within a month after delivery.

Other factors, including alcohol use and sleep deprivation, may trigger symptoms or make them worse. Improving sleep or eliminating alcohol use in these cases may relieve symptoms.

Treatment for Restless Legs Syndrome

Treatment for RLS is targeted at easing symptoms. In people with mild to moderate restless legs syndrome, lifestyle changes, such as beginning a regular exercise program, establishing regular sleep patterns, and eliminating or decreasing the use of caffeine, alcohol, and tobacco, may be helpful. Treatment of an RLS-associated condition also may provide relief of symptoms.

Other non-drug RLS treatments may include:

Leg massages
Hot baths or heating pads or ice packs applied to the legs
Good sleep habits
A vibrating pad called Relaxis
Medications may be helpful as RLS treatments, but the same drugs are not helpful for everyone. In fact, a drug that relieves symptoms in one person may worsen them in another. In other cases, a drug that works for a while may lose its effectiveness over time.

Drugs used to treat RLS include:

  • Dopaminergic drugs, which act on the neurotransmitter dopamine in the brain.
  • Mirapex, Neupro, and Requip are FDA-approved for treatment of moderate to severe RLS. Others, such as levodopa, may also be prescribed.
  • Benzodiazepines, a class of sedative medications, may be used to help with sleep, but they can cause daytime drowsiness.
  • Narcotic pain relievers may be used for severe pain.
  • Anticonvulsants, or antiseizure drugs, such as Tegretol, Lyrica, Gabapentin ( Neurontin ), and Horizant.

Although there is no cure for restless legs syndrome, current treatments can help control the condition, decrease symptoms, and improve sleep.

Usual Adult Dose for Restless Legs Syndrome

Gabapentin enacarbil available under the trade name Horizant (R):
600 mg orally once daily with food at about 5 PM

What Ingredients Are in Gabapentin?

Gabapentin is an anti-epileptic drug, also called an anticonvulsant. It affects chemicals and nerves in the body that are involved in the cause of seizures and some types of pain.

Gabapentin
Gabapentin

Some inactive ingredients in the gabapentin tablets or capsules include:

      • Lactose
      • Talc
      • Cornstarch
      • Gelatin
      • Colors such as FD&C blue no. 2, yellow iron oxide
      • Titanium dioxide
      • Poloxamer 407
      • Magnesium stearate
      • Copovidone, cornstarch
      • Candelilla wax
      • Hydroxypropyl cellulose

Dosing information

Usual Adult Dose for Epilepsy:

Initial dose: 300 mg orally on day one, 300 mg orally 2 times day on day two, then 300 mg orally 3 times a day on day three
Maintenance dose: 300 to 600 mg orally 3 times a day
Maximum dose: 3600 mg orally daily (in 3 divided doses)
-Maximum time between doses in the 3 times a day schedule should not exceed 12 hours

-The safety and effectiveness of gabapentin available under the trade name Gralise or Horizant in patients with epilepsy has not been studied.

Use: Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization

Usual Adult Dose for Postherpetic Neuralgia:

-Initial dose: 300 mg orally on day one, 300 mg orally 2 times day on day two, then 300 mg orally 3 times a day on day three
-Titrate up as needed for pain relief
-Maximum dose: 1800 mg per day (600 mg orally 3 times a day)
Gabapentin available under the trade name Gralise:
-Maintenance dose: Gralise should be titrated to 1800 mg orally once daily with the evening meal.
-Recommended titration schedule:
Day 1: 300 mg orally with the evening meal
Day 2: 600 mg orally with the evening meal
Days 3 through 6: 900 mg orally with the evening meal
Days 7 through 10: 1200 mg orally with the evening meal
Days 11 through 14: 1500 mg orally with the evening meal
Day 15: 1800 mg orally with the evening meal

COMMENT:
-Gralise is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration.

Gabapentin enacarbil extended release tablets are available under the trade name Horizant:

-The recommended dosage is 600 mg orally 2 times a day. Therapy should be initiated at a dose of 600 mg orally in the morning for 3 days of therapy, then increased to 600 mg 2 times a day (1200 mg/day) on day four.

COMMENT:
Gabapentin enacarbil extended release tablets available under the trade name Horizant and gabapentin are not interchangeable.

Use: Postherpetic neuralgia

Usual Adult Dose for Restless Legs Syndrome:

Gabapentin enacarbil available under the trade name Horizant:
600 mg orally once daily with food at about 5 PM

Use: For the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS) in adults

Usual Pediatric Dose for Epilepsy:

Less than 3 years: Not recommended

Greater than or equal to 3 and less than 12 years:
Starting Dose: Ranges from 10 to 15 mg/kg/day in 3 divided doses
Effective Dose: Reached by upward titration over a period of approximately 3 days; the effective dose in patients 5 years of age and older is 25 to 35 mg/kg/day in divided doses (3 times a day).

The effective dose in pediatric patients ages 3 and 4 years is 40 mg/kg/day and given in divided doses (3 times a day). Gabapentin may be administered as the oral solution, capsule, or tablet, or using combinations of these formulations. Dosages up to 50 mg/kg/day have been well tolerated in a long term clinical study. The maximum time interval between doses should not exceed 12 hours.

Greater than 12 years:
-Initial dose: 300 mg orally on day one, 300 mg orally 2 times a day on day two, then 300 mg orally 3 times a day on day three
-Maintenance dose: 900 to 1800 mg orally in 3 divided doses; the dose may be increased up to 1800 mg/day. Dosages up to 2400 mg/day have been well tolerated in long term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. The maximum time between doses in the three times a day schedule should not exceed 12 hours.

Use: Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization in patients 3 years of age and older

Gabapentin is used together with other medicines to treat partial seizures in adults and children at least 3 years old.

Gabapentin is also used to treat neuropathic pain (nerve pain) caused by herpes virus or shingles (herpes zoster) in adults.

Use only the brand and form of gabapentin your doctor has prescribed. Check your medicine each time you get a refill to make sure you receive the correct form.

The Gralise brand of gabapentin is indicated for the management of neuropathic pain only. It is not used for epilepsy.

Horizant is used to treat nerve pain and restless legs syndrome (RLS).

The Neurontin brand is used to treat seizures in adults and children who are at least 3 years old, in addition to neuropathic pain.

Gabapentin is part of its own drug class, called gabapentinoids. Typical dosages range from 100 milligrams to 800 milligrams of the drug.

 

Can I drive or ride a bike after I take Gabapentin ?

Gabapentin is used with other medications to prevent and control seizures. It is also used to relieve nerve pain following shingles (a painful rash due to herpes zoster infection) in adults.

Gabapentin is known as an anticonvulsant or antiepileptic drug.

You may feel sleepy, tired or dizzy when you first start taking gabapentin. This may also happen if your dose has increased.

If this happens to you, do not drive or ride a bike until you feel better.

It’s an offence to drive a car if your ability to drive safely is affected. It’s your responsibility to decide if it’s safe to drive. If you’re in any doubt, do not drive.

If you have epilepsy, you are generally not allowed to drive until:

    • you have not had any seizures (while awake) for 1 year
    • you have only had seizures while you’re asleep

If you change your epilepsy medicine, your doctor will tell you whether you need to stop driving and for how long.

What is the Action Mechanism of Gabapentin ? Is Gabapentin Addictive ?

What is the Action Mechanism of Gabapentin ?

signs someone is addicted to gabapentin

The chemical structure of gabapentin (Neurontin) is derived by addition of a cyclohexyl group to the backbone of gamma-aminobutyric acid (GABA). Gabapentin prevents seizures in a wide variety of models in animals, including generalized tonic-clonic and partial seizures.

The exact mechanism of action with the GABA receptors is unknown; however, researchers know that gabapentin freely passes the blood-brain barrier and acts on neurotransmitters.

Gabapentin has a cyclohexyl group to the structure of neurotransmitter GABA as a chemical structure. Even though it has a similar structure to GABA, it does not bind to GABA receptors and does not influence the synthesis or uptake of GABA.

Gabapentin works by showing a high affinity for binding sites throughout the brain correspondent to the presence of the voltage-gated calcium channels, especially alpha-2-delta-1, which seems to inhibit the release of excitatory neurotransmitters in the presynaptic area which participate in epileptogenesis.

Even though there is no evidence for direct action at the serotonin, dopamine, benzodiazepine, or histamine receptors, research has shown gabapentin to increase total-blood levels of serotonin in healthy control subjects.

The elimination half-life of gabapentin is 5 to 7 hours, and it takes two days for the body to eliminate gabapentin from its system.

One benefit of gabapentin use is its mild side-effect profile. The most common side effects are fatigue, dizziness, and headache.

Gabapentin has no activity at GABAA or GABAB receptors of GABA uptake carriers of brain. Gabapentin interacts with a high-affinity binding site in brain membranes, which has recently been identified as an auxiliary subunit of voltage-sensitive Ca2+ channels. However, the functional correlate of gabapentin binding is unclear and remains under study.

Gabapentin crosses several lipid membrane barriers via system L amino acid transporters. In vitro, gabapentin modulates the action of the GABA synthetic enzyme, glutamic acid decarboxylase (GAD) and the glutamate synthesizing enzyme, branched-chain amino acid transaminase.

Results with human and rat brain NMR spectroscopy indicate that gabapentin increases GABA synthesis. Gabapentin increases non-synaptic GABA responses from neuronal tissues in vitro. In vitro, gabapentin reduces the release of several mono-amine neurotransmitters.

Gabapentin prevents pain responses in several animal models of hyperalgesia and prevents neuronal death in vitro and in vivo with models of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Gabapentin is also active in models that detect anxiolytic activity.

Although gabapentin may have several different pharmacological actions, it appears that modulation of GABA synthesis and glutamate synthesis may be important.

Is Gabapentin Addictive ?

Asking about the signs someone is addicted to gabapentin first begs the question: What is gabapentin?

To answer that question requires putting gabapentin in perspective as a pharmaceutical drug that, while providing relief to thousands of people for nerve pain, also has the potential for abuse. It isn’t an opioid, but it has found a niche audience among those who take it recreationally, and for doctors who began to seek alternatives to narcotics as the opioid epidemic reached its apex, it seemed like a safer alternative.

In 2016, gabapentin was the 10th most prescribed drug in the United States, with 64 million prescriptions written that year . That was up from 39 million prescriptions written only four years earlier, in large part because “gabapentin, an anticonvulsant and analgesic for postherpetic neuralgia, has been thought to have no abuse potential despite numerous published reports to the contrary,” according to a 2018 article in the journal Psychology of Addictive Behaviors.

In that particular article, researchers analyzed data from a study of drug users in Kentucky who reported using gabapentin for non-medical purposes. Their findings? “Overall, the sample reported having initiated gabapentin more than 10 years earlier after having it prescribed for a legitimate, though generally off-label, medical indication (e.g., pain, anxiety, opioid detoxification). Participants reported use of gabapentin in combination with buprenorphine, other opioids, cocaine, and caffeine to produce sought-after central nervous system effects (e.g., muscle relaxation, pain reduction, sleep induction, feeling drunk, and feeling ‘high’).”

Gabapentin, such studies reveal, can be problematic. Whether used in conjunction with other drugs or on its own, it can be abused, which makes it a substance of concern. To understand the signs someone is addicted to gabapentin, however, requires some knowledge of what it is, where it comes from, how it works and how it can be addictive.

Comparative Studies

Gabapentin and lamotrigine have been compared in an open, parallel-group, add-on, randomized study in 109 patients with uncontrolled partial epilepsy and learning disabilities. The two drugs were similarly efficacious, with similar incidences of adverse events and serious adverse events. Neither lamotrigine nor gabapentin exacerbated any of the challenging behaviors observed in these patients.

The most common adverse reaction to gabapentin was somnolence, which was mostly reported during the initial titration phase.

In a double-blind comparison of gabapentin and lamotrigine in 309 patients with new-onset partial or generalized seizures, the target doses were gabapentin 1800 mg/day and lamotrigine 150 mg/day.

Severe adverse events were reported in 11% of patients taking gabapentin and 9.3% of patients taking lamotrigine. Two patients had serious adverse events thought to be related to the study drug; one took an overdose of gabapentin and the other had convulsions with lamotrigine. The most frequent treatment-related adverse events in both treatment groups were dizziness, weakness, and headache; 11% of patients taking gabapentin and 15% of those taking lamotrigine withdrew because of adverse events. There was an increase of over 7% in body weight from baseline in 14% of the patients taking gabapentin and 6.6% of those taking lamotrigine. There were benign rashes in 4.4% of those taking gabapentin and 11% of those taking lamotrigine.

The hypothesis that both amitriptyline and gabapentin are more effective in relieving neuropathic pain than diphenhydramine has been tested in a randomized, double-blind, triple crossover, 8-week trial in 38 adults with spinal cord injuries [18]. Maximum daily doses were 2600 mg for gabapentin and 150 mg for amitriptyline.

Amitriptyline was more efficacious in relieving neuropathic pain than diphenhydramine. Withdrawal because of possible adverse reactions occurred five times during gabapentin treatment:

(1) shortness of breath;

(2) dizziness, fatigue, and nausea;

(3) increased spasticity and pain;

(4) fatigue, drowsiness, constipation, and dry mouth; and

(5) severe itching.

The four most frequent adverse events were dry mouth, drowsiness, fatigue, and constipation, which were all more common with amitriptyline.

 

Take Gabapentin as an Anticonvulsant

Anticonvulsants (also commonly known as antiepileptic drugs or as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain.

Anticonvulsants suppress the rapid and excessive firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain. Some investigators have observed that anticonvulsants themselves may cause reduced IQ in children.   However these adverse effects must be balanced against the significant risk epileptic seizures pose to children and the distinct possibility of death and devastating neurological sequelaesecondary to seizures.

Anticonvulsants are more accurately called antiepileptic drugs (abbreviated “AEDs”), and are often referred to as antiseizure drugs because they provide symptomatic treatment only and have not been demonstrated to alter the course of epilepsy.

Gabapentin (Neurontin) has been approved as adjunctive therapy in adults with partial seizures with or without secondary generalization . Begin with 300 mg daily; increase to 900 to 1,800 mg daily given every 6 to 8 hours.  Side Effects maybe: Somnolence, fatigue, ataxia, dizziness, gastrointestinal upset, dyspnea.

A gamma-aminobutyric acid (GABA) analog, gabapentin does not interact with GABA receptors. Its mechanism of action is unknown.

Gabapentin is well absorbed orally, circulates mostly unbound in the plasma and is excreted unchanged in the kidneys without appreciable metabolism in the body. Oral bioavailability is approximately 60 percent and is not affected by food. The half-life is five to seven hours and is related to the creatinine clearance. Therefore, excretion is decreased in patients with renal impairment and decreased cardiac function, and in elderly patients. Gabapentin can be removed from the system through hemodialysis.

In clinical studies,  gabapentin was found to be effective in adults with refractory partial seizures and was also effective in preventing the progression of partial seizures to generalized tonic-clonic seizures.

Because gabapentin has no known pharmacokinetic interactions with any other antiepileptic drugs, it is useful in patients taking other antiepileptic medication.