Gabapentin may cause weight gain, but it is a rare side effect. Gabapentin is used to treat epilepsy.
It’s also taken for nerve pain, which can be caused by different conditions, including diabetes and shingles. Nerve pain can also happen after an injury.
In epilepsy, it’s thought that gabapentin stops seizures by reducing the abnormal electrical activity in the brain.
With nerve pain, it’s thought to block pain by affecting the pain messages travelling through the brain and down the spine.
Gabapentin is available on prescription. It comes as tablets, capsules and a liquid that you swallow.
Studies have shown that a small number of people taking gabapentin, a drug used to treat epilepsy and postherpetic neuralgia, experienced weight gain. People who do gain weight may gain about 5 pounds after 6 weeks of use.
In people with epilepsy, weight gain occurred in 3% of people older than 12 years of age who were taking gabapentin (compared to 2% of people taking the placebo). Weight gain was also seen at a similar rate in pediatric epilepsy patients who were 3 to 12 years old.
In people with postherpetic neuralgia, 2% of patients taking gabapentin experienced weight gain. No weight gain was found among people taking the placebo.
The cause of weight gain with gabapentin is likely due to increased appetite. You may be hungry more often. In some cases, weight gain may be due to fluid retention, another side effect of gabapentin. Another possible cause is not getting enough exercise if gabapentin is causing fatigue.
Some ways to avoid weight gain include:
Eating a healthy and balanced diet
Eating smaller portion sizes
Avoiding high-calorie snacks and desserts like chips, pastries and sweets
Eating low-calorie snacks like fruits and vegetables to manage hunger
Getting regular exercise
Swelling from fluid retention may be reduced by:
Sitting with your feet raised
Avoiding standing for long periods of time
If gabapentin is causing you to gain weight, do not stop taking this drug on your own. Stopping the drug suddenly can lead to serious problems, especially if you are taking gabapentin for seizures. Abruptly stopping a seizure medicine can cause seizures that won’t stop.
Weight gain is one of many possible side effects. The most common side effects with gabapentin include:
Clumsiness
Viral infection
Sleepiness
Nausea and vomiting
Speaking difficulties
Tremor
Swelling, usually involving the legs and feet
Fatigue
Fever
Movements that are jerky
Coordination difficulties
Double vision
Unusual eye movement
Detail Side Effects of Gabapentin
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
More common
Clumsiness or unsteadiness
continuous, uncontrolled, back-and-forth, or rolling eye movements
More common in children
Aggressive behavior or other behavior problems
anxiety
concentration problems and change in school performance
crying
depression
false sense of well-being
hyperactivity or increase in body movements
rapidly changing moods
reacting too quickly, too emotional, or overreacting
restlessness
suspiciousness or distrust
Less common
Black, tarry stools
chest pain
chills
cough
depression, irritability, or other mood or mental changes
fever
loss of memory
pain or swelling in the arms or legs
painful or difficult urination
sore throat
sores, ulcers, or white spots on the lips or in the mouth
swollen glands
unusual bleeding or bruising
unusual tiredness or weakness
Incidence not known
Abdominal or stomach pain
blistering, peeling, or loosening of the skin
clay-colored stools
coma
confusion
convulsions
dark urine
decreased urine output
diarrhea
difficult or troubled breathing
dizziness
fast or irregular heartbeat
headache
increased thirst
irregular, fast or slow, or shallow breathing
itching or skin rash
joint pain
large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
loss of appetite
muscle ache or pain
nausea
pale or blue lips, fingernails, or skin
red skin lesions, often with a purple center
red, irritated eyes
unpleasant breath odor
vomiting of blood
yellow eyes or skin
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
Blurred vision
cold or flu-like symptoms
delusions
dementia
hoarseness
lack or loss of strength
lower back or side pain
swelling of the hands, feet, or lower legs
trembling or shaking
Less common or rare
Accidental injury
appetite increased
back pain
bloated or full feeling
body aches or pain
burning, dry, or itching eyes
change in vision
change in walking and balance
clumsiness or unsteadiness
congestion
constipation
cough producing mucus
decrease in sexual desire or ability
dryness of the mouth or throat
earache
excess air or gas in the stomach or intestines
excessive tearing
eye discharge
feeling faint, dizzy, or lightheadedness
feeling of warmth or heat
flushed, dry skin
flushing or redness of the skin, especially on the face and neck
frequent urination
fruit-like breath odor
impaired vision
incoordination
increased hunger
increased sensitivity to pain
increased sensitivity to touch
increased thirst
indigestion
noise in the ears
pain, redness, rash, swelling, or bleeding where the skin is rubbed off
passing gas
redness or swelling in the ear
redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
runny nose
sneezing
sweating
tender, swollen glands in the neck
tightness in the chest
tingling in the hands and feet
trouble sleeping
trouble swallowing
trouble thinking
twitching
unexplained weight loss
voice changes
vomiting
weakness or loss of strength
weight gain
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Gabapentin is commonly used to treat some types of nerve pain but is classified as an anticonvulsant medicine, not as an opioid or painkiller.
Gabapentin was first approved in 1993 and is used to treat:
postherpetic neuralgia, a nerve pain caused by the shingles virus (herpes zoster),
restless legs syndrome (RLS), a painful movement disorder in the legs
partial seizures in adults and children at least 3 years old who have epilepsy
Gabapentin works by affecting chemicals and nerves in the body that are involved in the cause of seizures and in some types of nerve pain.
Gabapentin is not a federally-controlled drug substance and does not contain an opioid (narcotic) medication. However, gabapentin misuse and abuse has been reported, and it may be restricted in some states through their state drug-monitoring program. Gabapentin abuse can boost the high a person gets from opioid painkillers, muscle relaxants, and anxiety medications. This can be dangerous and potentially life-threatening.
In 2019, the FDA issued an alert that serious breathing problems have been reported with gabapentin and other related drugs, like Lyrica (pregabalin) in people at risk of slowed breathing.
This includes people who use opioid pain medicine or CNS depressants, people with chronic obstructive pulmonary disease (COPD, and the elderly.
These serious breathing problems may be fatal.
Read more about this serious FDA warning here.
Avoid or limit the use of alcohol (in beverages or medicines) with gabapentin as it can worsen drowsiness or dizziness. Ask you doctor about drinking alcohol while you are taking gabapentin.
What type of pain does gabapentin treat?
Gabapentin is approved by the FDA to treat:
Postherpetic neuralgia: nerve pain that can occur due to an outbreak of shingles. Shingles, also known as herpes zoster, occurs when the chicken pox virus deep-seated in your nerve activates again later in life and causes a serious skin rash. Not everyone gets postherpetic neuralgia from shingles, but it can be painful if you do. It causes a burning nerve pain that lasts for months, or even years, after the rash and blisters have cleared up.
Restless legs syndrome (RLS): an uncontrollable urge to move your legs around, often at night. This is usually due to leg discomfort. It may occur most often when you are sitting, laying down, or during bedtime. It can be disruptful to sleep and travel. It is thought RLS may occur due to an imbalance of the chemical dopamine in the brain.
Gabapentin has also been used off-label for the treatment of other types of neuropathic (nerve) pain like peripheral diabetic neuropathy, fibromyalgia and trigeminal neuralgia. “Off-label” uses of gabapentin are uses that have not been approved by the FDA and are not found in the package insert, but may have been accepted for use by healthcare providers based on clinical use.
How does gabapentin come?
There are several brand names of gabapentin including Gralise, Horizant, and Neurontin. Use only the brand and form of gabapentin your doctor has prescribed.
Gralise (gabapentin) is indicated for the management of postherpetic neuralgia only. It is not used for epilepsy. Gralise comes as a 300 and 600 milligram (mg) extended-release (ER) tablet and in a 30-day starter pack of 78 tablets. A generic option is not yet available.
Horizant (gabapentin enacarbil) is used in adults to treat either nerve pain due to postherpetic neuralgia (PHN) or restless legs syndrome (RLS). Horizont is also an extended-release 300 mg or 600 mg tablet and is not interchangeable with other gabapentin products. A generic option is not yet available.
Neurontin (gabapentin) is an immediate-release form used to treat seizures in adults and children who are at least 3 years old, in addition to nerve pain due to shingles. It comes as 100, 300, or 400 mg oral capsules; 600 mg and 800 mg oral tablets, and as a 250 mg per 5 mL oral solution. It is also available as a generic option.
Some brands are only used for certain conditions, and these products may not be interchangeable. Check your medicine each time you get a refill to make sure you have received the correct form.
Some of these medicines may be expensive. Ask your healthcare provider if you are able to use a generic form of gabapentin for your condition (this may not always be possible). Generic options could save you hundreds of dollars each month, or may be less expensive than your insurance copay.
Also, check with the manufacturer who may offer copay cards or patient assistance programs to lessen your overall costs, if you qualify. Be sure to check for online coupons, too, that can save you money on both generics and brands.
To learn more about gabapentin, join the Drugs.com gabapentin Support Group and Q&A Section where you can ask questions, share experiences and keep up with the latest news.
This is not all the information you need to know about gabapentin for safe and effective use and does not take the place of talking to your doctor about your treatment. Review the full gabapentin information here, and discuss this information and any questions you have with your doctor or other health care provider.
In the quest to find effective preventive migraine treatments, healthcare providers sometimes prescribe medications “off-label.” In these cases, a drug has been approved by the U.S. Food and Drug Administration (FDA) for one disorder, but has been found to have positive effects on an unrelated one.
Gabapentin is one such drug. It’s an anti-seizure drug sometimes used to prevent migraines, though there is conflicting scientific evidence supporting its effectiveness in this regard.
In the United States, gabapentin is sold in generic form and under the brand names Neurontin, Gralise, Horizant, and Neuraptine.
Gabapentin has an average rating of 8.0 out of 10 from a total of 105 ratings for the treatment of Migraine. 80% of reviewers reported a positive effect, while 11% reported a negative effect.
As a migraine sufferer since I was 13 yrs old. I am now 56 yrs old. I tried it all. Imitrex, Fiorinol, Maxalt, Fioricet, Relpax, Zomig, Treximet, Cafergot, you name it. Sometimes I ended up in the E.R for a shot of Toradol. Finally I saw a general practitioner. He put me on gabapentin, 400 mg 3x a day. What a miracle. I’ve been on it for over a year now and been TOTALLY headache free. Wish all my other doctors were up with this. Would have saved me a lot of suffering.
Gabapentin is available in a generic version but also comes under the brand names of Horizant, Neurontin, and Gralise. It’s available orally as a liquid solution, capsule, or tablet for extended or immediate release. It can be taken with or without food.
How It Works
Gabapentin is actually an anticonvulsant drug. It’s usually used as a seizure preventative for patients with epilepsy, or to alleviate the nerve pain of shingles. Anticonvulsants are a class of drugs designed to soothe nerve impulses. However, gabapentin is sometimes used for migraine prophylaxis (or prevention).
The precise mechanism of gabapentin’s action is not well known. Even though this drug has a similar structure to a brain neurotransmitter called GABA (gamma-aminobutyric acid), it has no effect on its receptors. It is believed that gabapentin blocks calcium channels, modulating the release of excitatory neurotransmitters.
Gabapentin and Migraine Prevention
Being an anticonvulsant, the theory behind using gabapentin for migraines is that its ability to calm nerve impulses could help avert migraine pain. Gabapentin could ease the brain’s electrical activities by settling excitatory neurotransmitters and blocking calcium channels.
However, this is mostly theoretical. Gabapentin’s exact role in migraine prevention isn’t well understood by researchers, and more research is needed to figure out what makes it work.
Gabapentin isn’t usually prescribed as a primary migraine preventative. It’s typically added to work in conjunction with other therapies, or used when other medications haven’t worked for the patient. As a preventative measure rather than an acute treatment, gabapentin needs to be taken continuously.
Gabapentin for Migraines Is an “Off-Label” Use
When a drug is used for something other than its purpose approved by the FDA, it’s called an off-label use. Since the FDA regulates the approval and testing of drugs (and not how doctors choose to prescribe them), your doctor is allowed to prescribe gabapentin for migraines if it seems like the right solution.
Gabapentin is primarily used to treat epilepsy in people older than 12 and partial seizures in children ages 3 to 12. It is also FDA-approved to treat a condition called postherpetic neuralgia—the nerve-related pain complication of a herpes zoster attack (shingles) that can occur in adults.3
Besides these uses, gabapentin is used off-label for a variety of other conditions like migraine prevention, as well as diabetic neuropathy, restless legs syndrome, and fibromyalgia.
Because of its benefit in treating these and other issues, gabapentin is what’s known as an adjuvant analgesic—a drug that can help control pain, despite it not being primarily intended to do so. Gabapentin may be used alone or with other medications when necessary.
It’s important to note, however, that The American Academy of Neurology (AAN) and the American Headache Society (AHS) do not list gabapentin as “effective” or “probably effective” for preventing migraines in their 2012 guidelines. Instead, gabapentin is given a level U rating, which means the evidence is conflicting or inadequate to support or refute its use for migraine prevention.
Gabapentin for Migraine Dosages
While gabapentin is prescribed under the care of a doctor, be careful to take only the recommended amount, and talk to your doctor about how to wean off of it if that becomes necessary.
What the Research Says
The research behind gabapentin for migraines is a bit mixed, but does show some promise.
The American Academy of Neurology (AAN) released a statement in 2013 which said there was insufficient evidence supporting gabapentin for migraine prophylaxis.
In 2014, a study conducted on gabapentin for episodic migraine found that some other antiepileptic drugs could be considered first-line migraine preventatives, but found inadequate evidence to recommend gabapentin for migraine prevention, saying it’s “not effective and commonly causes adverse effects.”
A 2016 study of gabapentin for headache disorders did reveal some benefit. However, it stopped short of recommending it as a primary migraine therapy.
How should I take gabapentin?
Take gabapentin exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take in larger or smaller amounts or for longer than recommended.
If your doctor changes your brand, strength, or type of gabapentin, your dosage needs may change. Ask your pharmacist if you have any questions about the new kind of gabapentin you receive at the pharmacy.
Both Gralise and Horizant should be taken with food.
Neurontin can be taken with or without food.
If you break a Neurontin tablet and take only half of it, take the other half at your next dose. Any tablet that has been broken should be used as soon as possible or within a few days.
Swallow the capsule or tablet whole and do not crush, chew, break, or open it.
Measure liquid medicine carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).
Do not stop taking this medicine suddenly, even if you feel fine. Stopping suddenly may cause increased seizures. Follow your doctor’s instructions about tapering your dose.
In case of emergency, wear or carry medical identification to let others know you have seizures.
This medicine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using gabapentin.
Store both the tablets and capsules at room temperature away from light and moisture.
Store the liquid medicine in the refrigerator. Do not freeze.
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
Side Effects of Gabapentin
LIke many other FDA-approved drugs, gabapentin could have side effects for many patients. Those include:
Swelling of feet or limbs
Unexpected or atypical eye movements
Loss of coordination
Blurry vision or other vision changes
Better Options for Migraine Prevention
There are plenty of migraine preventative drugs on the market which you can discuss with your doctor.
And as you probably know, living a healthy lifestyle could also help you reduce the migraine attacks you have to endure. Getting plenty of sleep, a healthy diet, and physical activity are all important.
Many migraine relief tools could reduce your suffering when you’re hit with a migraine, or help ward off more of them. These include supplemental Vitamin B2 and magnesium, which could help reduce migraine frequency. Axon Optics glasses, which have been shown to help 85% of users, are at the top of our list.
Interactions
Drinking alcohol may make some side effects of gabapentin more severe.
Types of drugs that are known to interact with gabapentin and may cause problems include:
Opiate pain medications, including Vicodin (hydrocodone) and morphine, among others
Naproxen (Aleve, Naprosyn, and others)
Medications used for heartburn, including Mylanta, Maalox, and cimetidine
If you do dipstick tests to check your urine for protein, tell your healthcare provider. Gabapentin may affect the results.
Your healthcare provider can advise you on whether you should avoid taking certain drugs with gabapentin entirely, or if the timing or dosage simply need to be adjusted.
Contraindications
Currently, there is not enough research or well-controlled studies on humans to deem this medication safe for expecting mothers.3 Contact your healthcare provider to discuss whether the benefits of use may outweigh the risks in your case.
Gababentin should be avoided by people with chronic kidney disease or myasthenia gravis.
Does gabapentin help nerve pain?
Gabapentin is approved to treat the type of nerve pain (neuralgia) that results from nerve damage. Gabapentin is used to treat neuralgia caused by a herpes zoster viral infection, also known as shingles. This pain is called post-herpetic neuralgia (PHN), and it can be severe and chronic. Gabapentin is also used to treat pain from diabetic neuropathy, which happens when nerves in the feet damaged by diabetes cause chronic burning pain.
The exact way that gabapentin works to relieve pain is not known. It may change the way the body senses and reacts to pain. Gabapentin is used to manage long-term (chronic) pain, not to be taken for pain as needed. Chronic pain can interfere with sleep and work, and lead to depression.
Studies show that pain relief may start within one week and reach a maximum effect in about 4 weeks. It can take this long because gabapentin is usually started at a low dose and gradually increased over time until it works.
For treating neuralgia, gabapentin is often started at 300 mg per day and gradually raised by 300 mg per day. One 2017 review of 37 studies found that pain relief usually occurs at a dose of 1,200 mg or more.
The same review compared gabapentin to an inactive medicine (placebo) in almost 6,000 adults with chronic pain from PHN or diabetic neuropathy. Study participants were given either gabapentin or a placebo for 4 to at least 12 weeks. The results showed that 30-40% of people taking gabapentin were able to reduce their pain by half or more, compared to 10-20% of people taking the placebo.
Although some people may get significant relief, others may have side effects without relief of pain. More than half of people taking gabapentin did not get significant relief and had side effects from the drug.
According to the review, about 60% of people taking gabapentin had side effects, including:
Dizziness
Sleepiness
Water retention (edema)
Clumsiness while walking (ataxia)
It does not typically make pain worse: In trials comparing gabapentin side effects to placebo side effects, only 1% of people reported increased pain, and this was the same for gabapentin and placebo.
Once you find the dose that relieves neuralgia for you, it is important not to stop taking it suddenly. Stopping suddenly can lead to withdrawal symptoms such as:
Gabapentin is a prescription drug. It comes as an oral capsule, an immediate-release oral tablet, an extended-release oral tablet, and an oral solution.
Gabapentin oral capsule is available as the brand-name drug Neurontin. It’s also available as a generic drug. Generic drugs usually cost less than the brand-name version. In some cases, the brand-name drug and the generic version may be available in different forms and strengths.
Why Gabapentin is Used
Gabapentin oral capsule is used to treat the following conditions:
Seizures: Gabapentin is used to treat partial (focal) seizures. It’s taken together with other seizure medications in adults and in children 3 years of age and older who have epilepsy.
Postherpetic neuralgia: This is pain from nerve damage caused by shingles, a painful rash that affects adults. Shingles appears after infection with the varicella zoster virus. This virus occurs in people who have had chicken pox.
Gabapentin may be used as part of a combination therapy. This means you may need to take it with other drugs.
Gabapentin Dosage for Adults
For adults, the gabapentin dosage can vary widely depending on the condition being treated. Upon starting treatment with gabapentin, the starting dose may be 100 to 300 mg per day and steadily increase until an effective dose is reached. The maximum dosage will depend on the condition being treated.
Standard gabapentin dosage for adults: 300-600 mg taken three times per day.
Maximum gabapentin dosage for adults: 1200 mg taken three times per day for a maximum daily dose of 3600 mg.
Gabapentin Dosage Chart for Adult
Indication
Age
Standard dosage
Maximum dosage
Partial seizures
12 years and older
300-600 mg three times per day
3600 mg per day
5-11 years
25-35 mg/kg (11.4-15.9 mg/lb) per day divided into three daily doses
50 mg/kg (22.7 mg/lb) per day
3-4 years
40 mg/kg (18.2 mg/lb) per day divided into three daily doses
50 mg/kg (22.7 mg/lb) per day
Postherpetic neuralgia
18 years and older
300 mg on day 1, 300 mg twice daily on day 2, then 300 mg three times daily on day 3; dosage may be further increased after day 3 to 600 mg three times per day
1800 mg per day
Diabetic peripheral neuropathy
18 years and older
300-1200 mg three times per day (off-label)
3600 mg per day
Fibromyalgia
18 years and older
600 mg twice daily and 1200 mg at bedtime (off-label)
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.