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

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 10^th 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.

Gabapentin is Used to Treat Seizures and Postherpetic Neuralgia ?

What is gabapentin?

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 it’s used

Currently, gabapentin has FDA approval for:

- Postherpetic neuralgia
- Adjunctive therapy in the treatment of partial seizures with or without secondary generalization in patients over the age of 12 years old with epilepsy, and the pediatric population, 3 to 12 year-olds with a partial seizure
- Moderate to severe restless leg syndrome (RLS) moderate to severe

It also has off-label use for neuropathic pain, fibromyalgia, bipolar disorder, postmenopausal hot flashes, essential tremors, anxiety, resistant depressant and mood disorders, irritable bowel syndrome (IBS), alcohol withdrawal, postoperative analgesia, nausea and vomiting, migraine prophylaxis, headache, interstitial cystitis, painful diabetic neuropathy, social phobia, generalized tonic-clonic seizures, pruritus (itching), insomnia, post-traumatic stress disorder (PTSD), and refractory chronic cough.

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.

Nerve pain can be a symptom of many different conditions, including cancer, HIV, diabetes, and shingles. For some, nerve pain is frustrating; for others, nerve pain is devastating and life-changing.

Whether it feels like burning, pinpricks, or sudden shocks of electricity, nerve pain can disrupt your life at home and at work. It can limit your ability to get around. Over time, it can grind you down. Studies show that people with nerve pain have higher rates of sleep problems,anxiety, and depression.Your nervous system is involved in everything your body does, from regulating your breathing to controlling your muscles and sensing heat and cold.

There are three types of nerves in the body:

1. Autonomic nerves. These nerves control the involuntary or partially voluntary activities of your body, including heart rate, blood pressure, digestion, and temperature regulation.
2. Motor nerves. These nerves control your movements and actions by passing information from your brain and spinal cord to your muscles.
3. Sensory nerves. These nerves relay information from your skin and muscles back to your spinal cord and brain. The information is then processed to let you feel pain and other sensations.

Because nerves are essential to all you do, nerve pain and damage can seriously affect your quality of life.

When you have a serious medical condition such as cancer or HIV, dealing with the additional misery of nerve pain can be especially hard. But there is good news. While nerve pain can’t always be cured, it can be treated — and there are a lot of good options available.

Experts believe that 40 million Americans are living with nerve pain. The impact of nerve pain is tremendous. Both the costs to the healthcare system as well as loss of wages and productivity are staggering.

What is Postherpetic Neuralgia ?

Postherpetic neuralgia (post-hur-PET-ik noo-RAL-juh) is the most common complication of shingles. The condition affects nerve fibers and skin, causing burning pain that lasts long after the rash and blisters of shingles disappear.

The chickenpox (herpes zoster) virus causes shingles. The risk of postherpetic neuralgia increases with age, primarily affecting people older than 60. There’s no cure, but treatments can ease symptoms. For most people, postherpetic neuralgia improves over time.

How Are Nerve Pain and Nerve Damage Treated?

In many instances, nerve damage cannot be cured entirely. But there are various treatments that can reduce your symptoms. Because nerve damage is often progressive, it is important to consult with a doctor when you first notice symptoms. That way you can reduce the likelihood of permanent damage.

Often, the first goal of treatment is to address the underlying condition that’s causing your nerve pain or nerve damage. This may mean:

- Regulating blood sugar levels for people with diabetes
- Correcting nutritional deficiencies
- Changing medications when drugs are causing nerve damage
- Physical therapy or surgery to address compression or trauma to nerves
- Medications to treat autoimmune conditions

Additionally, your doctor may prescribe medications aimed at minimizing the nerve pain you are feeling. These may include:

- Pain relievers
- Tricyclic antidepressants
- Certain anti-seizure drugs – Gabapentin

Complementary and alternative approaches may also help alleviate your nerve pain and discomfort. These include:

- Acupuncture
- Biofeedback
- Hypnosis
- Meditation

Dosage for postherpetic neuralgia

Adult dosage (ages 18–64 years)

- Typical starting dosage: Day 1, 300 mg; day 2, 600 mg (300 mg two times per day, spaced evenly throughout the day); day 3, 900 mg (300 mg, three times per day, spaced evenly throughout the day). Your doctor may further increase your dosage after day 3.
- Maximum dosage: 1,800 mg per day (600 mg, three times per day, spaced evenly throughout the day)

Child dosage (ages 0–17 years)

Dosage for people younger than 18 years has not been established.

Senior dosage (ages 65 years and older)

Your kidney function may decrease with age. Your body may get rid of this drug more slowly. Your doctor may start you on a lower dose so that too much of this drug does not build up in your body. Too much of the drug in your body can be dangerous. Your doctor may change your dose based on how well your kidneys are working.

Gabapentin in Non-Epilepsy Neuropathic Pain like Postherpetic Neuralgia

The FDA approved gabapentin for the management of postherpetic neuralgia in adults. Recently, gabapentin underwent systemic evaluation in the management of diabetic neuropathy. In 1998, Rowbotham and his research team concluded that in 229 postherpetic neuralgia patients, gabapentin had more significant pain reduction as early as two weeks after initiating the treatment.

Furthermore, other measurements of mood, depression, anger-hostility, fatigue, and physical functioning, were more effectively managed with gabapentin compared to placebo.

During the same time, Backonja reviewed the effect of gabapentin in 165 diabetic neuropathy patients and showed the result that pain reduction in the gabapentin group is greater (as measured with an 11-point Likert scale) in comparison to the placebo group. And the results were significant from 2 weeks of initiation of therapy and stayed significant during the eight weeks of study.

Patients in the treatment group also reported improvement in their quality of life. This medication was well tolerated in 67% of patients who received a maximum daily dosage of 3600 mg.

Treatment for Postherpetic neuralgia

Postherpetic neuralgia is a nerve disease occurs after an attack of herpes zoster infection. Herpes zoster or ‘shingles’ is a viral infection which affects the skin, especially sides of the chest, caused by varicella zoster virus. This is the same virus which causes chicken pox in children.

After an episode of herpes, the virus remains dormant in the nerve tissues of the body. This virus may become active when the immunity of the individual reduces or during convalescence after a major illness, resulting in blisters on the skin, known as shingles. It is accompanied with a rash which disappears without major consequences in about two to four weeks. Around 50% of individuals with shingles go on to develop post herpetic neuralgia (PHN) or after-shingles pain.

The neuralgia begins when the herpetic eruptions begin to heal. The pain appears usually in the affected dermatone or the affected nerve course and results in severe pain in the region which has the same nerve supply. The pain is a drawing, pricking type of intense pain, sometimes accompanied with burning sensation of the skin. The pain lasts from a few weeks to few months, rarely years.

Causes

- - Severe rash within three days of shingles infection
  - A study shows that, 65% of patients were women
  - The chances of developing PHN, increases when the shingles occurs in persons over 50 years.
  - The incidence of herpes zoster is up to 15 times higher in HIV-infected patients than in uninfected persons, and as many as 25 percent of patients with Hodgkin’s lymphoma develop herpes zoster.
  - Blacks are one fourth as likely as whites to develop this condition.
  - Site of HZ involvement
    - Lower risk – Jaw, neck, sacral, and lumbar
    - Moderate risk – Thoracic
    - Highest risk – Trigeminal (especially ophthalmic division), brachial plexus.

Signs and symptoms:

- A pain that continues for 3 months or more, after the healing of shingles, is defined as PHN.
- PHN pain may be burning, aching, itching and sharp and the pain can be constant or it can come and go
- The skin which was affected with blisters, may show scarring
- The involved dermatome may show altered sensations, either hypersensitivity or reduced sensitivity.
- In rare cases, where if the nerves involved also control muscle movement, the patient might also experience muscle weakness, tremor or paralysis

Postherpetic Neuralgia Treatment:

The conventional treatment is directed at pain control while waiting for the condition to resolve. Pain therapy may include multiple interventions, such as topical medications, over-the-counter analgesics, tricyclic antidepressants, anticonvulsants and a number of non medical modalities. Occasionally, narcotics may be required.

When it comes to treating postherpetic neuralgia, you may need to take a combination of medications to effectively manage your pain and other PHN symptoms. No single treatment plan is right for everyone—what medications you take will depend on your PHN symptoms.

While symptoms differ from person to person, for most people, PHN does improve over time. Researchers found that more than half of all patients with PHN stop experiencing pain within one year.¹

Fortunately, during that period of intense pain and other symptoms, there are certain medications that you can take to significantly help control postherpetic neuralgia symptoms.

Before trying a prescription medication, your doctor will most likely want you to try an over-the counter (OTC) analgesic (painkiller) medication, such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs). These medications can help relieve pain and other PHN symptoms.

Tylenol is an example of acetaminophen, and Advil is an example of an NSAID you can take to help treat PHN.

Another OTC medication you may want to try for PHN is capsaicin cream. This cream—made from hot chili pepper seeds—is applied to the affected skin, and it can be helpful for reducing PHN-related pain. But this cream can be painful, so talk to your doctor about how much you should apply.

If these medications aren’t strong enough to treat your PHN symptoms, your doctor may suggest some of the prescription medications below to treat your postherpetic neuralgia.

- Tricyclic antidepressants, such as amitriptyline (Elavil), nortriptyline (Pamelor), and desipramine (Norpramin) are effective at treating postherpetic neuralgia pain. Other classes of antidepressant are also helpful. All classes of antidepressant take a few weeks to start working.
- Anticonvulsants, developed to control seizures, can help reduce the pain of PHN. These include gabapentin (Neurontin), carbamazepine (Tegretol) and pregabalin (Lyrica). Gabapentin enacarbil (Horizant) and gabapentin (Gralise) are approved by the FDA for the treatment of PHN in adults.
- Anti-viral drugs valacyclovir and acyclovir are also becoming medications of choice for treating postherpetic neuralgia.
- Lidocaine Patches for Postherpetic Neuralgia. Lidocaine patches are FDA-approved to treat PHN. The medication in the patch—lidocaine—can penetrate your skin and go to the nerves that are sending the pain signals. A benefit of lidocaine patches is that they don’t numb the skin.
- Prescription capsaicin patches. These patches contain a very high concentration of the chili pepper extract capsaicin. The capsaicin patch Qutenza is applied in a doctor’s office for one hour every three months.

If you have severe pain and other medications don’t work for you, your doctor may want you to try an opioid. Tramadol (eg, Ultram) is an example of a relatively weak opioid that can be used to help you manage PHN. Your doctor may have you try a weaker opioid first. Opioids, such as morphine (MS Contin), oxycodone (OxyContin), and hydrocodone (Vidocin), are also used to treat moderate to severe pain of postherpetic neuralgia.

Homoeopathic Medicine:

Mezereum – For Postherpetic Neuralgia with Intense Burning

Mezereum is rated among the best medicines for postherpetic neuralgia. It is the best-suited prescription when postherpetic neuralgic pains are violent and attended with marked burning. Mezereum is the most helpful among medicines for postherpetic neuralgia in postherpetic pains located in the face. The pain in the face may get worse while eating.

Warmth brings relief. Mezereum is also helpful during active herpes zoster where eruptions are present. The key symptoms to look out for before prescribing Mezereum during herpes zoster infection are violently itching vesicles with shining red areola and intense burning.

2. Ranunculus Bulbosus – For Pains coming in Paroxysms

Another of the prominently indicated medicines for postherpetic neuralgia is Ranunculus Bulbosus. It is indicated for sharp, shooting, postherpetic neuralgic pains that come in paroxysms.

It is also one of the top listed medicines for intercostal neuralgia following herpetic infection. Ranunculus Bulbosus is also indicated for herpes zoster when the vesicles eruptions are bluish in colour. The eruptions are attended with itching and burning symptoms which worsen on contact.

3. Rhus Tox – One of the best Medicines for Postherpetic Neuralgia

Rhus Tox also figures on the list of highly effective medicines for postherpetic neuralgia. It is one of the best medicines for postherpetic neuralgia where the pains are attended with marked restlessness. The skin is sensitive to cold air in such cases. In herpes zoster, Rhus Tox is the most preferred among medicines when the vesicles are yellowish with itching and stinging.

How and When to Take Gabapentin ?

Gabapentin is a prescription medicine. It’s important to take it as advised by your doctor.

Dosage and strength

Each capsule of gabapentin contains 100mg, 300mg or 400mg of gabapentin. Each tablet contains 600mg or 800mg of gabapentin.

If you’re taking gabapentin as a liquid, 2ml is usually the same as taking a 100mg tablet or capsule. Always check the label.

Dosage for epilepsy

The usual dose for:

- adults and older children (aged 12 and over) is 900mg to 3,600mg a day, split into 3 doses
- younger children (aged 6 to 12) – varies depending on their weight

Dosage for nerve pain

The usual dose to treat nerve pain in adults is 900mg to 3,600mg a day, split into 3 doses.

Changes to your dose

To prevent side effects, your doctor will prescribe a low dose to start with and then increase it over a few days. Once you find a dose that suits you, it will usually stay the same.

How to take Gabapentin ?

Swallow gabapentin capsules and tablets whole with a drink of water or juice. Do not chew them.

You can take gabapentin with or without food, but it’s best to do the same each day.

Try to space your doses evenly through the day. For example, you could take it first thing in the morning, early afternoon and at bedtime.

If you or your child are taking a liquid, it will come with a plastic syringe or spoon to measure your dose. If you do not have a syringe or spoon, ask your pharmacist for one. Do not use a kitchen spoon, as it will not measure the right amount.

How long to take it for

If you have epilepsy, it’s likely that once your condition is under control you’ll still need to take gabapentin for many years.

If you have nerve pain, once your pain has gone you’ll continue to take gabapentin for several months or longer to stop it coming back.

If you forget to take it

If you forget a dose, take it as soon as you remember. If it’s within 2 hours of the next dose, it’s better to leave out the missed dose and take your next dose as normal.

Never take 2 doses at the same time. Never take an extra dose to make up for a forgotten one.

If you have epilepsy, it’s important to take this medicine regularly. Missing doses may trigger a seizure.

If you forget doses often, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

If you take too much

Taking too much gabapentin can cause unpleasant side effects.

Urgent advice: Contact 111 for advice or go to A&E now if:

you take more than your prescribed dose of gabapentin and:

- you feel dizzy or sleepy
- you have double vision
- you start slurring your words
- you have diarrhoea
- you pass out (faint)

If you need to go to A&E, take the gabapentin packet or leaflet inside it, plus any remaining medicine, with you.

Stopping gabapentin

It’s important not to stop taking gabapentin suddenly, even if you feel fine. Stopping gabapentin suddenly can cause serious problems.

If you have epilepsy, stopping gabapentin suddenly can cause seizures that will not stop.

If you’re taking it for any reason and stop suddenly, you may have a severe withdrawal syndrome. This can have unpleasant symptoms, including:

- anxiety
- difficulty sleeping
- feeling sick
- pain
- sweating

It’s possible to prevent withdrawal seizures and other symptoms by gradually reducing the dose of gabapentin.

Do not stop taking gabapentin without talking to your doctor – you’ll need to reduce your dose gradually.

Gabapentin Interactions With Other Medications and Substances

Gabapentin can interact with other prescription and over-the-counter medications, vitamins, and herbal supplements.

People should be sure to give a doctor a full list of their current medications and supplements before taking gabapentin.

The results of another 2017 review suggest that the following are some of the main substances that interact with the drug:

- caffeine, which is present in tea, coffee, and cola
- ethacrynic acid, which is a diuretic
- losartan, which is a medication for high blood pressure
- magnesium oxide, which is a mineral supplement and antacid
- mefloquine, which is an antimalarial drug
- morphine, which is an opioid pain medication
- phenytoin, which is an anti-seizure medication

If gabapentin causes sleepiness, a person should speak with a doctor before taking other medications that can also cause drowsiness, including:

- antianxiety medications
- antidepressants
- antihistamines
- cold and flu medications
- muscle relaxers
- narcotics, which are pain medications
- sleeping pills

Presence of other health conditions

To ensure that gabapentin is safe to take, a person should tell a doctor if they also currently have or have ever had:

- diabetes
- dialysis treatment
- drug or alcohol misuse issues
- heart disease
- kidney disease
- liver disease
- seizures (if taking gabapentin for conditions unrelated to seizures)

Gabapentin oral capsule can interact with several other medications. Different interactions can cause different effects. For instance, some can interfere with how well a drug works, while others can cause increased side effects.

Below is a list of medications that can interact with gabapentin. This list does not contain all drugs that may interact with gabapentin.

Before taking gabapentin, be sure to tell your doctor and pharmacist about all prescription, over-the-counter, and other drugs you take. Also tell them about any vitamins, herbs, and supplements you use. Sharing this information can help you avoid potential interactions.

If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.

Opioids

When used with gabapentin, opioids can cause dangerous effects in the body. Some examples of these drugs include morphine, hydrocodone, and oxycodone.

Taking gabapentin with an opioid increases your risk for severe sleepiness, respiratory depression, coma, and even death.

Stomach acid drugs

When used with gabapentin, certain drugs used to treat stomach acid problems can reduce the amount of gabapentin in your body. This can make it less effective. Taking gabapentin 2 hours after taking these drugs can help prevent this problem. Examples of these drugs include:

aluminum hydroxide
magnesium hydroxide

The gabapentin dosage your doctor prescribes will depend on several factors. These include:

the type and severity of the condition you’re using gabapentin to treat
your age
the form of gabapentin you take
other medical conditions you may have

Typically, your doctor will start you on a low dosage and adjust it over time to reach the dosage that’s right for you. They’ll ultimately prescribe the smallest dosage that provides the desired effect.

The following information describes dosages that are commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to suit your needs.

What is the Maximum Daily Dosage of Gabapentin?

I’m taking 800mg three times a day for anxiety. It works great. The max recommended dose is 3600mg daily, but I’ve read where some people take up to 4800mg a day. I guess it depends on the person and how they metabolize it.

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

This medicine comes with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

If you are using Gralise® tablets:

These should be taken with the evening meal.
Swallow the tablet whole. Do not crush, break, or chew it.

For patients with epilepsy who take gabapentin three times per day, do not allow more than 12 hours to pass between any 2 doses. The medicine works best if a constant amount is in the blood.

Neurontin® capsules, tablets, and solution may be taken with or without food.

You may break the scored Neurontin® tablets into two pieces, but make sure you use the second half of the tablet as the next dose. Do not use the half-tablet if the whole tablet has been cut or broken after 28 days. Ask your doctor or pharmacist if you have any questions.

Swallow the capsule whole with plenty of water. Do not open, crush, or chew it.

Measure the oral liquid using a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

If you take an antacid that contains aluminum or magnesium, wait at least 2 hours before taking gabapentin. Some examples of these antacids are Di-Gel®, Gaviscon®, Gelusil®, Maalox® and Mylanta®.

Only use the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage forms (capsules, liquid, and tablets):
- For epilepsy:
  - Adults and children 12 years of age and older—At first, 300 milligrams (mg) three times per day. Your doctor may adjust your dose as needed and tolerated. However, the dose is usually not more than 1800 mg per day (600 mg three times per day).
  - Children 3 to 11 years of age—Dose is based on body weight and must be determined by your doctor. The starting dose is 10 to 15 milligrams (mg) per kilogram (kg) of body weight per day and divided in 3 doses. Your doctor may adjust your dose as needed and tolerated.
  - Children younger than 3 years of age—Use and dose must be determined by your doctor.
- For postherpetic neuralgia:
  - Adults— At first, 300 milligrams (mg) as a single dose in the evening. Your doctor may adjust your dose as needed and tolerated. However, the dose is usually not more than 1800 mg per day.
  - Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

You should store the Neurontin® oral liquid in the refrigerator. Do not freeze.

Although the FDA says 3600mg/day in most places, they have a more extensive doc about gabapentin/neurontin usage and bioavailability. First, your body can only process a certain amount taken and the rest is excreted, so large doses over their bioavailablity chart don’t give larger effects.

Lyrica and other meds have different bioavailability, so use smaller dosages. Since your kidneys do much of the work with gaba/neurontin, you want to make sure you do not have any kidney problems.

A person may need lower doses or not use it due to that. Second, calcium channel meds like gabapentin are nonlinear, so side effects and benefits vary from person to person.

What works or doesn’t work for one, may be the opposite for another. That is why dosage benefits and side effects vary so much from person to person. Even a small dose might make you sleep, but not to another person.

I have heard from some people their doc may prescribe smaller doses during the day and a larger dose at the time of day more problems appear such as at night.

Gaba/neurontin has a short half life so needs doses spread out during the day. One challenging thing is that people that are on gaba are also on other meds too, so there is going to be confusion about what caused what and if there are interactions.

After a couple years, I was only on gaba. For me on maximum dose, I did sleep more, plus several other side effects. It all comes down to finding the most benefit with the least negatives including cost or as docs say, benefits outweigh the risks. Suggest reading more of this forum for a patient viewpoint.

Does Gabapentin Cause Constipation?

Gabapentin may cause constipation, but it is not a common side effect. In clinical trials of adults taking gabapentin for nerve pain, only about 4% of people reported constipation.

Gabapentin belongs to a class of drugs called anticonvulsants. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

It’s not fully understood how gabapentin works. For postherpetic neuralgia, it seems to prevent the increase in sensitivity to pain that occurs. For seizures, it may alter the effect of calcium (low levels of calcium may cause seizures).

Who may not be able to take gabapentin

Gabapentin is not suitable for some people.

To make sure it’s safe for you, tell your doctor if you:

- have ever had an allergic reaction to gabapentin or any other medicine
- have ever misused or been addicted to a medicine
- are trying to get pregnant or are already pregnant
- are on a controlled sodium or potassium diet, or your kidneys do not work well (gabapentin liquid contains sodium and potassium, so speak to your doctor before taking it)

Some people in these trials took an inactive medicine (placebo). About 2% of people taking a placebo also reported constipation, so the actual percentage of people with constipation while taking gabapentin is probably less than 4%.

In clinical trials of people aged 12 and over taking gabapentin for seizure disorder, about 2% reported constipation as a side effect. Out of people taking a placebo, 1% also reported constipation.

In the clinical trials of gabapentin to treat nerve pain in adults, the most common side effects were:

Dizziness
Sleepiness
Swelling in the hands or feet (peripheral edema)

In clinical trials of people older than 12 taking gabapentin to treat a seizure disorder, the most common side effects were sleepiness and clumsiness (ataxia).

Thoughts of death or suicide is another rare but important side effect of gabapentin, occurring in about 1 in 500 people. These thoughts can happen within one week of starting gabapentin. Call your doctor right away if you have any unusual changes in mood or behavior, or any of these symptoms:

Thoughts about suicide or dying
Suicide attempt
Depression, new or worsening
Anxiety, new or worsening
Panic attacks

In 2019, the U.S. Food and Drug Administration (FDA) added another important warning about gabapentin: When this drug is taken with opioid pain medication or used by a person with chronic lung disease like chronic obstructive pulmonary disease (COPD), it may cause severe and possibly fatal difficulty breathing (respiratory depression). Before starting gabapentin, let your doctor know if you are taking any opioid drug, or if you have been diagnosed with a lung disease.

Even if you have side effects from gabapentin, it is important not to stop taking it suddenly on your own. This medication must be reduced over time (tapered) by your doctor. Stopping suddenly can lead to withdrawal symptoms such as:

Anxiety
Insomnia
Nausea
Pain

If you are taking gabapentin to control seizures, stopping suddenly may increase your risk of a seizure.

Does Gabapentin Help you Sleep?

Gabapentin is a prescription medication that may help you sleep. That may be why it has been prescribed for people with insomnia, even though it is not approved for that use.

Gabapentin is an anti-convulsant medication that inhibits the release of excitatory neurotransmitters, allowing for its use against pathologic neurotransmission such as that seen in neuropathic pain and seizure disorders. It has a wide therapeutic index, with doses in excess of 8000 mg/kg failing to cause a fatal reaction in rats.

Gabapentin is ineffective in absence seizures and should be used in caution in patients with mixed seizure disorders involving absence seizures. Gabapentin has been associated with drug reaction with eosinophilia and systemic symptoms (DRESS), otherwise known as multi-organ hypersensitivity. This reaction can prove fatal and early symptoms such as fever, lymphadenopathy, and rash should be promptly investigated.

Gabapentin is available on prescription. It comes as tablets, capsules and a liquid that you swallow.

Key facts

You’ll usually take gabapentin 3 times a day. You can take it with or without food.
Most people who take gabapentin do not get any side effects. But some people may feel sleepy, tired and dizzy. Common side effects are usually mild and go away by themselves.
It takes at least a few weeks for gabapentin to work.
Most people do not have to stay on the same brand of gabapentin as there’s very little difference between brands.
Some people can become addicted to gabapentin after taking it for a long time. When stopping gabapentin you’ll need to reduce your dose gradually to avoid withdrawal symptoms.
If you have epilepsy, you are entitled to free prescriptions for all the medicines you take, not just your epilepsy ones. You can get an application form from your doctor’s surgery.

However, gabapentin enacarbil (Horizant) has been approved by the Food and Drug Administration (FDA) to treat a sleep disorder called restless legs syndrome (RLS).

One of the most common side effects of gabapentin is drowsiness.
In people taking gabapentin for its approved conditions (certain epileptic seizures and postherpetic neuralgia), 19% of patients older than 12 years of age with epilepsy and 21% of patients with postherpetic neuralgia reported drowsiness as a side effect.

Gabapentin and sleep

Most studies show that gabapentin improves slow wave sleep (“deep sleep”) and total sleep time.

Two small studies showed that gabapentin may help people with primary insomnia and occasional sleep disturbance improve total sleep time and wakefulness in the morning.
In other studies, it appears that gabapentin may improve sleep in people with other medical conditions that make it more difficult to sleep, such as alcohol dependence, hot flashes and bipolar disorder.

In a large review of 26 studies on gabapentin and sleep in patients with other medical conditions, the average dose taken daily was about 1,800 mg. Although positive sleep outcomes were reported, the researchers noted that gabapentin was not tolerated as well as placebo and some patients stopped taking it. Misuse and abuse of the drug has also been reported.

It takes about 2 to 3 hours for immediate-release gabapentin to reach its fullest effect, and it’s typically taken 3 times per day.

RLS treatment

Gabapentin may also be used to treat RLS, a disorder that makes it hard to fall asleep or stay asleep. RLS causes an uncontrollable and uncomfortable urge to move your legs, which is worse at night.

The FDA has approved gabapentin enacarbil (Horizant) — a long-acting gabapentin — as a treatment for RLS.

Side effects of gabapentin

The most common side effects with gabapentin include:

Clumsiness
Viral infection
Drowsiness
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
Serious reactions can include:
Difficulty breathing
Allergic reactions with swelling of the throat or face

Presence of Other Health Conditions That Affect Gabapentin

What is Neurontin?

Neurontin 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.

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

Neurontin is also used to treat seizures in adults and children who are at least 3 years old.

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.

To ensure that gabapentin is safe to take, a person should tell a doctor if they also currently have or have ever had:

- diabetes
- dialysis treatment
- drug or alcohol misuse issues
- heart disease
- kidney disease
- liver disease
- seizures (if taking gabapentin for conditions unrelated to seizures)

Who may not be able to take gabapentin

Gabapentin is not suitable for some people.

To make sure it’s safe for you, tell your doctor if you:

have ever had an allergic reaction to gabapentin or any other medicine
have ever misused or been addicted to a medicine
are trying to get pregnant or are already pregnant
are on a controlled sodium or potassium diet, or your kidneys do not work well (gabapentin liquid contains sodium and potassium, so speak to your doctor before taking it)

Gabapentin is also Used for Prevention of Fibromyalgia

Fibromyalgia is a muscular condition that affects many people. It refers to muscle fatigue and pain felt across different muscle groups in the body, not just on isolated areas.

Fibromyalgia is a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues.

The term fibromyalgia directly means pain that is embedded in the tissues of the muscles, specifically the fibrous tissues. This very acute pain starts from the ligaments, the tendons, and other such connective muscle tissues that are present all over the muscular system of the body. Researchers believe that fibromyalgia amplifies painful sensations by affecting the way your brain processes pain signals.

Fibromyalgia Symptoms sometimes begin after a physical trauma, surgery, infection or significant psychological stress. In other cases, symptoms gradually accumulate over time with no single triggering event.

Women are more likely to develop fibromyalgia than are men. Many people who have fibromyalgia also have tension headaches, temporomandibular joint (TMJ) disorders, irritable bowel syndrome, anxiety and depression.

There are however some controversial theories regarding Fibromyalgia that propose that this condition is a psychosomatic illness, that is, it is a disorder brought about by psychological factors and not necessarily physical factors. This reasoning is mainly brought about by the strong evidence available that relates Fibromyalgia to major depression.

An in-depth review regarding the association of major depression disorders with Fibromyalgia brought out significant similarities between the two in terms of psychological characteristics and neuroendoctrine abnormalities in the patients.

Researchers believe repeated nerve stimulation causes the brains of people with fibromyalgia to change. This change involves an abnormal increase in levels of certain chemicals in the brain that signal pain (neurotransmitters). In addition, the brain’s pain receptors seem to develop a sort of memory of the pain and become more sensitive, meaning they can overreact to pain signals.

Medications designed to treat epilepsy are often useful in reducing certain types of nerve pain. Gabapentin (Neurontin) is sometimes helpful in reducing fibromyalgia symptoms. Gabapentin is a medicine used to treat pain caused by nerves that are not working properly. Gabapentin changes the way that the nerves send messages to the brain. It can be taken in a tablet or a liquid, with or without food. Doses are usually 1200 mg to 2400 mg each day. At the start of treatment low doses are used to minimise side effects, but the dose is usually increased after a few weeks.

At the reviews of gabapentin for fibromyalgia in drugs.com , almost 70% Fibromyalgia Patients think Gabapentin can cure their fiobromyalgia disease. But almost 20% fiobromyalgia Patients think it doesnot work. ( Rating 1 -2 %), another 15% patients think it do work but the effect is not that good ( Rating 3 – 5 ).

One of the patient said:

“I have had fibro for 7 years, finally have a doctor that prescribed me Gabapentin. It’s amazing I feel like a normal person again. I sleep through the night, with no pain anymore. My anxiety is gone also, which is awesome. I know everyone is different, but it works for me. I have had little to no side effects yet. First few doses was a bit of an air head other than that no complaints. Being able to function pain free and agitation free is a blessing.”

Another Fiobro patient said:

“I had the best results, in relieving the pain, with gabapentin. I was able to work through the other symptoms. The etodolac helped with the inflammation. I was doing well, until the muscle spasms started, again. I suspect the mould allergies exasperated the symptoms. So, cyclobenzeprine was added. I don’t know what happened, but I was jobless, homeless, and very sick by the time a CVS pharmacist recognized the V.A. had put me on another toxic, prescription drug cocktail. When I brought it to the V.A.s attention, as usual, it was ignored. The medications that help, are the ones the V.A. will not prescribe to veterans like myself. They say speak up, if you do, expect to be classified as mentally ill, violent, aggressive, involuntarily committed”

NatalieW555 Said:
“I was suffering from fibromyalgia pain most of my adult life, I’m 52 by the way, not realizing there was this wonderful medication available to me…I started it about 2 years ago and it really makes a HUGE difference in how my body feels. I take 300 mg 3X daily. I hope it never quits working for me…you should give it a try….It has no side effects on me.”

Member Annabqnm Said:

“Pretty much saved my life. 13 years ago fibromyalgia symptoms (severe pain especially legs and shoulders), started. My father was taking high doses of gabapentin for chronic guillaune barre. He urged me to try it–and it was the first real sleep I had in months! My rheumatologist had me on 1600mg. 3x, gradually lowered to 1600 mg. 2x. Studies at Mayo Clinic and Johns Hopkins show very few (and very mild) side effects, even at high doses. The only problem I have is if I forget to take them. Then I get flu like symptoms. I was able to continue my career (elementary school teacher) with no problems. Retired this year age 66 and very active. BTW my memory seems better than most friends my age.”

But 30% Fibro customers think Gabapentin is not effective for their Fibro disease. I looked the reviews they have wrote, I found most of them are just back pain or leg pain but not Fiobromyalgia. But some Fibro patients do think it has some side effects, especially thought problems such as depression.

One of the Fibro patient said:

“I have “fibromyalgia,” severe muscle pain from a twisted spine/congenitally deformed vertebrae. I was getting better with yoga, but hurt my back/rib muscles overdoing. I developed depression on gabapentin after a few weeks. At first it dulled the pain and made me feel lightheaded, and I had memory problems. Then my anxiety increased and the pain continued, and hit a real low. I spent two weeks in a psych ward until a brilliant psych nurse who believed in treating muscle pain. I am now recovering on a mix of robaxin, a muscle relaxer, a low dose of valium for rib spasms, and prozac and remeron (for sleep) and hope to get off all of them once I can exercise again. Similar reaction to Lyrica four years ago.”

Gabapentin is effective for Fibro. But you need consider whether you can endure the side effects of gabapentin. Please check our website for the Gabapentin Side Effects.

Gabapentin Dosing for Neuropathic Pain

First, we must consider the different neuropathic pain types. Neuropathic pain can be diverse in nature, encompassing a wide range of pain types, including post-herpetic neuralgia (PHN), painful diabetic peripheral neuropathy (DPN), and painful cancer-related neuropathies.

Gabapentin has been shown to be beneficial in treating several types of neuropathic pain; however, the mechanism of action by which gabapentin exerts its analgesic effect is still unknown.

It is suggested that gabapentin may block the calcium channel alpha(2)delta (a2d)-1 receptor in the brain. This protein-modulated receptor is involved in excitatory synapse formation. Therefore, the therapeutic effects of gabapentin may be attributed to prevention of new synapse formations.

Gabapentin was shown to offer substantial improvement in neuropathic pain with side effects that were similar to those on placebo.

Even with sufficient data supporting the use of gabapentin in the treatment of various neuropathic pain conditions, gabapentin only has Food and Drug Administration (FDA) approval for PHN. Dosing recommendations for off-label use of gabapentin can be somewhat ambiguous, if a recommendation exists at all. Therefore, several studies further investigate dosing regimens specific to other neuropathic pain syndromes.

Gabapentin Dosing Considerations

Three gabapentin products are FDA approved to treat PHN. The different formulations cannot be interchanged and each has its own dosing schedule.

- For immediate-release gabapentin (Neurontin), dosing may be initiated with 300 mg on day 1, doubled on day 2 (300 mg twice a day), and tripled on day 3 (300 mg 3 times a day). The dose can then be titrated up as needed for pain relief to a maximum dose of 1,800 mg daily (divided into 3 daily doses). Clinical studies referenced in the package insert state that efficacy for a range of doses from 1,800 mg/day to 3,600 mg/day were observed; however, there was no additional benefit seen with doses greater than 1,800 mg/d.
- Gralise is an extended-release gabapentin formulation that also is FDA approved for PHN with a titration schedule that begins with 300 mg on day 1; 600 mg on day 2; 900 mg on days 3 to 6; 1,200 mg on days 7 to 10; 1,500 mg on days 11 to 14; and 1,800 mg on day 15 and thereafter.
- The third gabapentin formulation for PHN treatment is another extended-release product, Horizant. The starting dose is 600 mg in the morning for 3 days, increased to 600 mg twice daily on day 4 and thereafter. A daily dose of Horizant greater than 1,200 mg provided no additional benefit at the expense of side effects.

Several studies have evaluated off-label use of gabapentin in the treatment of other neuropathic pain conditions. A randomized, double-blind trial compared gabapentin to placebo in 135 patients with DPN over 8 weeks. The results showed a statistical benefit of gabapentin compared to placebo, at all end points, for pain improvement.

The gabapentin dosing regimen used in this study was 900 mg/d for week 1; 1,800 mg/d for week 2; 2,400 mg/d for week 3; and 3,600 mg/d for week 4. All the patients were titrated up to a dose of 3,600 mg/d, regardless of efficacy at lower doses. Patients who could not tolerate this dose were titrated down to the greatest tolerable dose.

Of the 84 patients randomized to the gabapentin group, 56 (67%) were able to tolerate 3,600 mg/d.During the first week, gabapentin resulted in improvement in sleep interference compared to placebo.

By the second week, gabapentin resulted in improvement in all pain rating scales compared to placebo. Of the 84 patients in the gabapentin group, 70 completed the study, and 7 patients withdrew due to adverse drug events (ADEs). Most ADEs reported in the gabapentin group were of mild or moderate intensity, and the most frequently reported effects were dizziness (23.8%), somnolence (22.6%), headache (10.7%), diarrhea (10.7%), confusion (8.3%), and nausea (8.3%).

A double-blind crossover study (n=40) assessed gabapentin for the treatment of DPN. The dose of gabapentin used in this trial was much lower, with patients titrated up every 3 days to a maximum dose of 900 mg/d. The end points evaluated in this study included level of pain on a visual analog pain scale (VAS), and scores on the present pain intensity scale, the McGill pain questionnaire (MPQ), and the global assessment of pain relief.

Statistical improvement between gabapentin and placebo was noted in only 1 end point, the MPQ score, with a mean reduction of 8.9 points for gabapentin compared to 2.2 points with placebo (P=0.03). No serious ADEs were noted, and the most common ADEs of gabapentin were drowsiness, fatigue, and imbalance. The results of this study suggest that gabapentin is not effective or is only minimally effective in treating painful DPN at a dose of 900 mg/d.⁵

A search in the Cochrane Database of Systematic Reviews was conducted to further examine dosing regimens for neuropathic pain. In a review analyzing 37 studies for gabapentin treatment in chronic neuropathic pain, the main outcome was Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) definitions for moderate and substantial benefit in chronic pain studies.⁶ These were defined as follows:

30% reduction in pain over baseline (moderate)
50% reduction in pain over baseline (substantial)
Much or very much improved on Patient Global Impression of Change (PGIC) (moderate)
Very much improved on PGIC (substantial)
Gabapentin was shown to be better than placebo across all studies for IMMPACT outcomes. The review concentrated on gabapentin doses of 1,200 mg/d or greater and reported that doses at or above this threshold were reasonably effective for treatment of various neuropathic pain types.

The upper threshold for maximum effective gabapentin doses ranged from 2,400 mg/d to 3,600 mg/d in the majority of studies reviewed.

ADEs and withdrawal rates for patients taking gabapentin doses of 1,200 mg/d or greater were compared to those for patients taking placebo in 20 studies with 4,125 participants. Common ADEs seen were somnolence, drowsiness, and sedation.

These occurred in 14% of participants in the gabapentin group versus 5% of those taking placebo. Data also showed gabapentin was associated with a higher incidence of dizziness (19% vs 5%), peripheral edema (7% vs 2.2%), and ataxia or gait disturbances (8.8% vs 1.1%).

The rate of serious events was similar between gabapentin and placebo groups. Twenty-two studies involving 4,448 patients reported on participant withdrawals due to ADEs, which occurred in 11% of patients taking gabapentin compared to 7.9% of those taking placebo.⁶

Postmarketing Abuse

Postmarketing reports have described symptoms of agitation, confusion, and disorientation upon abrupt withdrawal of gabapentin. Cases usually involve other potentiating factors, such as the use of higher than recommended doses for unapproved indications, a history of poly-substance abuse, or the use of gabapentin to relieve symptoms of withdrawal from other substances.¹In a study of postmortem toxicology, cases that tested positive for gabapentin or pregabalin were included to determine if abuse of these drugs contributed to the fatalities. Of the 13,766 cases investigated, 0.31% were positive for gabapentin. Of the gabapentin cases, 18.6% were considered abuse, and 4.7% were poisonings. An overwhelming majority of abuse cases (87.5%) also involved opioid intoxication, and 100% involved alcohol and/or opioids. In addition, a greater number of pregabalin cases were designated as abuse cases than gabapentin cases (48.1% vs 18.6%, respectively).⁷

Conclusion

Gabapentin has sufficient evidence showing its efficacy and safety in treating neuropathic pain. Effective treatment doses of gabapentin for neuropathic pain tend to be higher compared to effective treatment doses for other conditions. Gabapentin is a relatively safe medication. The most prevalent effects seen are drowsiness, somnolence, and sedation. It is necessary to start at lower doses of gabapentin and titrate up to a therapeutic dose. Ataxia and somnolence appear to exhibit a positive dose-response relationship; therefore, titrating the dose of gabapentin may help manage possible ADEs.