Gabapentin Is an Effective Treatment for Alcohol Withdrawal Symptoms?

Gabapentin is an anticonvulsive medication which first discovered in the 1970s in Japan. Its original use was as a muscle relaxer and anti-spasmodic medication, but later, it was discovered the potential of the medication as anticonvulsive medication and as an adjunct to stronger anticonvulsants. Gabapentin is an anticonvulsant medication that got FDA approval for partial seizure therapy in 1993. 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.

In one placebo-controlled, retrospective study that investigated the effects of gabapentin on about 700 patients with refractory partial seizure disorder, there was an improvement in overall well-being in patients. The effect prompted a controlled investigation of the drug in primary psychiatric conditions.

An important benefit of gabapentin is that there is no interaction with valproate, lithium, and carbamazepine. Also, gabapentin has minor side effects.

- A new study reports the nerve pain reliever gabapentin may be helpful in treating people with serious alcohol withdrawal symptoms.
- Some experts say gabapentin is most effective if used in combination with a benzodiazepine medication.
- Gabapentin can have serious side effects, including drowsiness and abnormal eye movements.

Gabapentin in Alcohol Withdrawal

For the first time, the DSM-V includes the diagnostic guidelines for alcohol dependency. There are a variety of severe diseases that result from or are influenced by alcohol dependence include stomach ulcers, liver issues, increased risk of heart disease, and neuropathy. Researchers assess that 3.8% of worldwide deaths result from direct or indirect effects of alcohol abuse.

While gabapentin’s mechanism of action is generally understood, it appears to be a logical pharmacologic option for treating issues involving the GABA receptor system. Gabapentin is a safe, readily available, and effective drug for alcohol-use disorder treatment, specifically for the abstinence maintenance phase. A 2014 trial bolstered the evidence base for gabapentin use in the treatment of alcohol use disorder. Results for insomnia and cravings, two symptoms of alcohol use disorder abstinence maintenance, demonstrated significant improvement with gabapentin pharmacotherapy. Gabapentin has also shown a statistical benefit when used as adjunctive therapy to naltrexone (the FDA-approved alcohol use disorder medication). It is also clear that higher doses of gabapentin, 1800 mg per day, seem to have a stronger effect on alcohol-use disorder abstinence maintenance. However, the trials investigating gabapentin as monotherapy have shown mixed results.

For gabapentin, unlike disulfiram and naltrexone, there is no need for hepatic dose adjustments. Gabapentin can also be used in patients whose renal function is below 20 mg/dl (although a dosing adjustment is needed).

In 2007, Melcolm and his team compared gabapentin to lorazepam. They concluded that there were significant reductions in self-reported sleep disturbance and daytime sleepiness in patients undergoing outpatient treatment for alcohol withdrawal.

A double-blind study investigated the use of 1200 mg/ per day gabapentin in alcohol use disorder. Specifically, the researchers found gabapentin to be superior to the benzodiazepine lorazepam in treating outpatients with moderate alcohol withdrawal. This outcome was measured by a lower chance of drinking and a superior, but clinically, similar alcohol withdrawal symptom reduction.

Can a drug used primarily to treat nerve pain and partial seizures be effective in helping ease alcohol withdrawal symptoms?

The anticonvulsant drug gabapentin is used off-label to treat alcohol-related withdrawal, cravings, anxiety, and insomnia. Although it is well tolerated and has demonstrated efficacy for mild alcohol withdrawal and early abstinence, there is concern about its potential for abuse. Gabapentin should be prescribed only as a second-line alternative to standard therapies, and only after screening for opioid or other prescription drug abuse to determine if heightened monitoring is warranted. Clinicians should be aware of gabapentin’s limitations for treating alcohol use disorder and be attentive to emerging data on risks and benefits.

A Trusted Source published this week concluded that gabapentin can relieve alcohol withdrawal symptoms but is most effective for people with a history of more severe symptoms after a few days of abstinence.

Gabapentin is known under brand names such as Neurontin, Gralise, and Horizant.

It was first developed Trusted Source in Japan during the 1970s and approved for use in the United States in 1993.

The drug was originally used as a muscle relaxer and antispasmodic medication. It’s been used off-label for other conditions.

“It has been used for detoxification — alcohol withdrawal — for many years,” said Dr. Raymond F. Anton, the study’s main author and a professor of medicine at the Medical University of South Carolina in Charleston.

“For relapse prevention, other clinical trials have had mixed results. We had published several studies suggesting it would be added to other medications with some success, but it looked like only in those with alcohol withdrawal symptoms prior to treatment,” he said.

“This study proved that gabapentin could work by itself as a relapse prevention medication, but only in this with the higher alcohol withdrawal symptoms, as predicted,” Anton told Healthline.

What the study revealed

Anton’s team looked at 90 people meeting the criteria of serious alcohol use.

Over 16 weeks, 12 of the 44 participants given gabapentin had no heavy drinking days (27 percent) compared with four (9 percent) of those participants given a placebo.

The study found mild to moderate side effects, including dizziness and some fatigue.

“Very few people had significant enough side effects to stop treatment,” Anton said. “It also improved sleep.”

Dr. Meredith Sagan, an addiction psychiatrist at Alo House Recovery Centers in Southern California, says gabapentin is most effective with benzodiazepine medications commonly used for withdrawal.

“Gabapentin cannot necessarily be used safely on its own to support such a detox,” Sagan told Healthline. “It’s always important to consult a medical professional when considering detoxifying from alcohol, as it can be very dangerous due to possible seizure and others risks.”

Individualized treatments

Sagan says the combination of medications and the timeline to take them is specific to each individual.

“Some people may need more or less medication, as well as different types and combinations, depending on their degree of alcohol consumption, in addition to other factors,” she said.

“So, although gabapentin can be a useful adjunct to the benzodiazepine category of medication for alcohol detox, it is not time to say goodbye to ‘benzos’ just yet,” Sagan said.

Benzodiazepines are also used to treat anxiety and seizures as well as to relax muscles. These medications come in many manufactured forms, including Xanax, Klonopin, Librium, Valium, and Ativan.

Participants in the South Carolina study weren’t allowed to take benzodiazepines or opioids.

“For people using gabapentin just for anxiety and not for alcohol withdrawal, gabapentin can be a good non-benzodiazepine alternative,” Sagan said.

“Gabapentin at higher doses can cause an uncomfortable withdrawal when one quits taking it. However, for some people with an addiction history, gabapentin is a safe alternative to benzodiazepines, which over the long term can be physically and psychologically addictive,” she said.

Gabapentin side effects

Common side effects of gabapentin include abnormal eye movements, clumsiness or unsteadiness, constipation, diarrhea, difficulty speaking, drowsiness, dry mouth, nausea, and vomiting.

More serious side effects — which may be more common in people with psychiatric disorders — include anger and violent behavior, increased anxiousness, depression, anxiety or irritability, mania, panic attacks, suicidal thoughts or behavior, and insomnia.

“I was prescribed gabapentin when I was struggling with my severely herniated disc,” Janine McKavish Thalblum, a resident of Dublin, California, told Healthline.

“The side effects were longer than an encyclopedia. With all the pain I was in I was borderline suicidal, so I opted not to take them, as that was one of the side effects. When the pharmacist was reading (them) before handing it over, I literally started to cry,” she explained.

Thalblum did take gabapentin for 2 days before opting out. She says she couldn’t tell if the medication contributed to her “overwhelming sense of wanting to give up.”

Andrea Johnson, a resident of Oakland, California, and her late wife, Julie, both took gabapentin for pain. They had vastly different experiences.

“She had chronic pain from her legs having been shattered in a car crash. Her doctors prescribed gabapentin about 10 years ago under its brand name of Neurontin,” Johnson told Healthline.

“She stopped it after a week because it put her into a constant dream state. She was sort of awake and could do things but without being conscious of what she was doing. When I caught her rolling a cigarette without realizing that she was doing it, I put a stop to the gabapentin and told her doctor why,” Johnson said.

Johnson’s doctor prescribed her gabapentin last year for arthritis in her hips.

“I was concerned about it because of Julie’s experience, but I didn’t get the psych effects that she did,” Johnson said. “By the end of a month, it still wasn’t having an effect on my pain either, so I stopped it.”

Gabapentin and opioids

In recent years, gabapentin has been involved in opioid overdose deaths and been dubbed “an emerging threat” in a national bulletin to law enforcement.

It’s listed as a controlled substance in some states, although officials say it’s usually not the main cause of death and not as dangerous as opioids.

Pfizer, which developed gabapentin, paid $430 million in 2004 under an agreement with government prosecutors over fraudulent claims the company was accused of making about the drug’s uses.

Anton says researchers are still looking at whether gabapentin can be used as an anti-craving drug like naltrexone.

“Right now, it is estimated that only 20 percent of individuals who might benefit from reducing or stopping drinking actually receive treatment,” Anton said.

“And, of those 20 percent, only 20 percent receive any medication-assisted treatment. The standard of care in the U.S. has historically been an AA (Alcohol Anonymous) or 12-step counseling model. While that model has helped many people, many others do not want to partake in it, or haven’t found it useful.

“Medications that can be prescribed by specialized and/or primary care providers can encourage many more people to consider treatment for their alcohol use disorder,” he added.

Gabapentin is a prescription anticonvulsant used to treat epileptic seizures, postherpetic neuralgia, and restless legs syndrome. Postherpetic neuralgia is pain caused by shingles, which can last many months after having the illness.

While the exact mechanism of action of gabapentin is not fully understood, it may work by decreasing excitatory brain signaling. This can prevent seizures and change the way the brain responds to pain signals. This medication can be found as a capsule, tablet, or oral solution.

The following 11 questions are designed to help you better understand your relationship to alcohol. They will help you to tell if it resembles abuse or addiction, or is if it closer to average.

1. Do you tend to drink more than you expected to? And for longer periods of time?

2. Do you wish you could drink less, and struggle to cut down your alcohol intake?

3. Does drinking consume much of your time? In other words, do you spend a lot of your time trying to obtain, use, or recover from alcohol hangovers?

4. Do you have very strong cravings or urges to drink? Does it feel like you “need” it to get by?

5. Does drinking cause problems for you at work, in school, or in your family obligations? Does this happen frequently?

6. If drinking does cause these social and interpersonal problems for you, do you continue to drink anyway?

7. Have you given up activities that used to be meaningful for you? For example, have you quit a sport or left friendships because you don’t seem to have the time or energy anymore?

8. Do you use alcohol even when it makes your activity physically dangerous? This could be drinking while driving, using certain prescription drugs, or working with heavy machinery.

9. Do you continue to drink even after discovering that it exacerbates, worsens, or even causes other physical or mental illnesses?

10. Are you developing a tolerance for alcohol? This could show up as a decreased effect after drinking the same quantity of alcohol that you used to use, or having to drink more and more alcohol to achieve the desired level of intoxication.

11. Have you experienced withdrawal symptoms after not drinking any alcohol for a while? These include a racing heart, trouble sleeping, shakiness, sweating, fever, restlessness, nausea, or even auditory or visual hallucinations? Does more alcohol relieve these feelings?

As an Addiction Treatment Medication

The medical research community has made great strides in synthesizing thousands of drugs over the years to treat physical ailments, mental illness, and other health conditions.

Addiction is just one of the many conditions that can be treated with specific medications. And while there are presently only a handful of FDA-approved medications used to manage substance dependence, gabapentin has been considered for off-label use for as an addiction treatment drug.

Different companies, including Parke-Davis, Greenstone, and Teva, manufacture several varieties of the generic drug. Other drugs that have been used to treat the symptoms of addiction withdrawal, for specific substances, include:

- Clondine
- Other anticonvulsants, such as Tegretol and Depakote
- Methadone and buprenorphine
- Naltrexone

Typical Application

Doses range from 100 mg to 800 mg. The frequency of administration may be based on various factors such as withdrawal symptom severity and withdrawal progress. The drug’s half-life is around 5-7 hours.

Gabapentin has been evaluated for use during medical detox and throughout subsequent treatment modalities to support relapse prevention while clients adjust to their new sober lifestyles.

Treating Substance Abuse

According to Medscape, gabapentin can inflict users with suicidal thoughts and abrupt changes in behavior. For this reason, it should only be used under medical supervision. It can also cause elevated blood pressure, fever, sleep problems, appetite changes, and chest pain.

While it has been used to treat addictions to other substances, gabapentin is most often used to treat alcoholism — an addiction some 16.6 million adults suffered from in 2013, per the National Institute on Alcohol Abuse and Alcoholism.

During withdrawal from alcohol abuse or dependency, clients may experience anxiety, tremors, agitation, and irritability. In order to understand how gabapentin works, there must be a basic understanding of how the brain works first. A balance of excitatory and inhibitory nervous system activity is, in part, mediated by neurotransmitters known as GABA and glutamate. Gabapentin may work by potentiating the inhibitory signaling of GABA and reducing the neural excitation associated with glutamate activity. As a result, signals for pain, agitation, and anxiety are reduced, too.

An American Journal of Psychiatry study showed impressive results during the 16-week treatment of 150 people who were dependent on alcohol, noting better results among those who were treated with both gabapentin and naltrexone than the latter alone. The Journal of Clinical Psychiatry reported on another study in which individuals treated for alcoholism with gabapentin showed a significant reduction in how much they drank and a greater rate of abstinence than those in the placebo group.

Gabapentin may have a similar calming effect on individuals who are detoxing from marijuana and benzodiazepines. Despite claims from fans of the plant-based drug, marijuana is indeed addictive. In 2012, 305,560 people checked into rehab citing cannabis as their primary drug of abuse, per the Substance Abuse and Mental Health Services Administration. One Neuropsychopharmacology study that analyzed the use of gabapentin in the treatment of marijuana addiction and withdrawal noted individuals in the gabapentin treatment group used less marijuana, had fewer withdrawal symptoms, and experienced improvements in cognitive functioning, compared to the placebo group.

While not quite as prevalent as a substance of abuse, benzodiazepines still accounted for 17,019 admissions to treatment in 2012, per SAMHSA. Individuals who have been abusing marijuana or benzodiazepines for a long period of time may have difficulty achieving a state of relaxation without those drugs, and gabapentin can help individuals remain calm while they’re recovering from addiction.

Managing Migraine Headaches

Migraine All kinds of Headache can literally bring your existence to a halt. Anybody who has ever experienced the pain triggered by a migraine will completely realize this statement.

Often involving only one side of the head, these All kinds of Headache could be extremely debilitating for the sufferer. They are able to make you nauseous, as well as be painful to the point that you simply vomit. Episodes can last from 12 to 72 hours, with small or no relief.

Many individuals experience an aura at the onset of a migraine. ” Lightning flashes” observed within the corner of the eye, dizziness, blurred or double vision, and nausea are a couple of from the classic tell-tale signs that a migraine is about to happen.

The pain is extreme, and a single will become ultra sensitive to sights and sounds. Light of any sort is excruciating. Individuals will usually need to lie down in a darkened, quiet room although they wait for that headache to subside.

Many women begin to encounter migraines because they go via menopause. They may have never had a migraine in their life, but discover that they are regular during this time. There’s no known reason why this would begin to occur only at this time of life. Frequently times the trigger is tension related, but might be brought on by particular points that a single eats. Physical illness might be an additional trigger, but no one knows for particular.

Medications are available to avoid migraine All kinds of Headache, or to relieve symptoms after the onset. Numerous individuals end up within the emergency room of the hospital considering that they are getting a stroke if the migraine is severe sufficient.

The signs and symptoms of blurred vision accompanied by the extreme head pain lead some people to think which they may have a brain tumor. Your doctor will most likely order an MRI to rule this out.

In case you endure from frequent migraines, lie down and use a cold compress on the forehead and also the back of your neck. Caffeine will also help to relieve the signs and symptoms by dilating the blood vessels.

Often a physician will prescribe certain drugs which are also utilized to deal with higher blood pressure, because they seem to possess an impact on the frequency and intensity of the migraine. Known as calcium channel blockers and Beta blockers, they’ve been utilized with some success within the past. These are used as preventive measures.

Your physician will operate with you to attempt to lessen the frequency from the migraines, even though some individuals will continue to have as numerous as 5 or 6 a week. Depending on how frequently you’ll have them is not something that can be predicted. Attempt to determine what it’s that you simply were performing before the headache occurred. Keep a list of things you consume that appear to precipitate the migraine.

Maintain your physician informed of your findings. By discovering out what the trigger from the migraines is will help to control them. even though the natural ways does not assist you to control the migraines, you will find medications on the market these days that a physician can prescribe to assist deal with the migraines. With that becoming said if you can control them without drug then it is suggested to do so.

Preventive Migraine Medications

These meds can:

- - Help you have fewer migraines.
  - Make your headaches less severe.
  - Make them shorter.

This type of treatment can help if you get migraines often.

You may want to consider preventive medications if:

- - The drugs you take to relieve your migraines don’t help or you have bad side effects from them.
  - You have 4 or more migraines a month.

The drugs that are used to prevent migraine include:

Anti-seizure drugs. These meds may work by calming nerve cells in the brain.

They include:

- - Gabapentin (Gralise, Horizant, Neurontin)
  - Topiramate (Qudexy XR,Trokendi XR, Topamax)
  - Valproic acid (Depakene, Depakote, Stavzor)

Beta-blockers usually treat high blood pressure and heart disease. It’s not clear how they help prevent migraines. Some that work for these headaches include:

- - Atenolol (Tenormin)
  - Metoprolol (Lopressor, Toprol XL)
  - Nadolol (Corgard)
  - Propranolol (Inderal, Innopran XL)
  - Timolol

Antidepressants. These medications affect the level of the brain chemical serotonin, which may be linked to migraines. Some of them, such as amitriptyline and venlafaxine, can help keep the headaches away. Other kinds may work, too.

CGRP Inhibitors: CGRP (calcitonin gene-related peptide) is a molecule involved in causing migraine pain. CGRP inhibitors are a class of drugs that block the effects of CGRP. They are specifically approved to prevent migraine attacks. You give yourself an injection once a month with a pen-like device. In clinical trials, people consistently had one to two fewer migraine days a month than those who took placebo. Mild pain and redness at the injection site are the most common side effects. These drugs are:

- - Atogepant (Qulipta)
  - Eptinezumab (Vyepti)
  - Erenumab (Aimovig)
  - Fremanezumab (Ajovy)
  - Galcanezumab (Emgality)

Atogepant (Qulipta) can be taken orally. Eptinezumab (Vyepti) is taken as an IV infusion every three months. Fremanezumab (Ajovy) can be taken every three months or once a month. For the others, you give yourself.

Triptans for menstrual-related migraines. These drugs treat migraines when they’re already happening, but one — frovatriptan (Frova) — may help prevent migraines that women get because of their menstrual cycle. The medicine affects serotonin levels and may also relieve pain in other ways.Botulinum toxin (Botox). Often used to treat wrinkles, it also helps some people who get migraines at least 15 days per month, called chronic migraines. It’s for people who have long-term migraine headaches, with the attack lasting 4 hours at a time or longer. Doctors think Botox may keep the brain from giving off chemicals that the body uses to send pain signals.

When you take medication to prevent migraines, keep these tips in mind:

- Your doctor will likely start you on a low dose and gradually increase it over time. It may take several months to find the best dose with the fewest side effects.
- Don’t suddenly stop taking preventive medications. That could trigger a rebound headache. If you do need to stop taking them, you’ll need to gradually taper off under your doctor’s care.
- These meds probably won’t completely get rid of your headaches. You may still need to take medicine when you do have one.

If you can’t take medication or wish not to, a device might be worth considering. Cefaly is a portable headband-like device that gives electrical impulses on the skin at the forehead. This stimulates a nerve associated with migraine headaches. Cefaly is used once a day for 20 minutes, and when it’s on you may feel a tingling or massaging sensation.SpringTM may be another option. You hold this device at the back of your head at the first sign of a headache, and it gives off a magnetic pulse that stimulates part of the brain. In addition, there is a noninvasive vagus nerve stimulator called gammaCore. When placed over the vagus nerve in the neck, it releases a mild electrical stimulation to the nerve’s fibers to relieve pain. Nerivio is a wireless remote electrical neuromoduat home.

Gabapentin Dosage Chart, Gabapentin Dosage for Adults and Gabapentin Dosage for Children

Gabapentin is a generic prescription drug that is FDA-approved as an add-on treatment with other medications for partial seizures in those with epilepsy.

It can also be used to treat nerve pain from postherpetic neuralgia (a complication of shingles). Gabapentin is frequently prescribed off-label for many other conditions, such as diabetic peripheral neuropathy, fibromyalgia, and alcohol dependence.

Gabapentin is typically prescribed as a generic, but the drug is also available under the brand names Neurontin and Gralise. Some patients may be prescribed drugs very similar to gabapentin—such as Horizant (gabapentin enacarbil) or Lyrica (pregabalin)—instead of gabapentin.

Gabapentin is taken as a tablet, capsule, or oral liquid. Dosing will depend on the condition being treated, age of the person being treated, and kidney function. The usual dose for epilepsy starts at 300 mg on the first day. The dose can then be increased until an effective dose is reached, which is usually 300 to 600mg taken three times per day.

Gabapentin dosage forms and strengths

Gabapentin is taken by mouth as a tablet, capsule, or oral solution.

- Tablets: 600 or 800 mg per tablet
- Capsules: 100, 300, or 400 mg per capsule
- Liquid: 250 mg per 5 milliliters (ml) oral liquid

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 for children

Gabapentin is FDA approved as a secondary treatment for partial seizures in children 3 years or older with epilepsy. The use of gabapentin in children for any other medical condition is not FDA-approved. Dosing will be determined by both the child’s age and weight.

by both the child’s age and weight.

Gabapentin dosage by age for children older than 3 years
Age (yr)	Recommended dosage
3-4 yrs	40 mg per kg (18.2 mg/lb) of body weight divided into three dosesMaximum: 50 mg per kg (22.7 mg/lb) of body weight daily
5-11 yrs	20-35 mg per kg (9.1-15.9 mg/lb) of body weight divided into three dosesMaximum: 50 mg per kg (22.7 mg/lb) of body weight daily
12 yrs or older	300-600 mg taken three times per dayMaximum: 3600 mg per day

Gabapentin dosage chart
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)	2400 mg per day
Alcohol dependence	18 years and older	300-600 mg three times per day (off-label)	1800 mg per day

Gabapentin dosage for partial seizures

Gabapentin is FDA approved as adjunctive therapy for partial seizures in adults and children 3 years of age or older.

Standard gabapentin dosage for adults: 300 to 600 mg taken three times per day by mouth.
Maximum gabapentin dosage for adults: 3600 mg daily in three divided doses.
Renally impaired patients (kidney disease)—dose amount and dose frequency adjustment:
1. Creatinine clearance of 30-59 ml/min: 200 to 700 mg twice per day
2. Creatinine clearance of 16-29 ml/min: 200 to 700 mg once per day
3. Creatinine clearance of 15 ml/min or less: 100 to 300 mg once per day decreased proportionately (1/15 per whole number value) for each decrease in creatinine clearance
4. Hemodialysis: dose is dependent on estimated creatinine clearance; a supplemental dose of 125 to 350 mg is given after dialysis

Gabapentin dosage for nerve pain due to shingles (postherpetic neuralgia)

Gabapentin is FDA approved to treat postherpetic neuralgia, that is, neuropathic pain due to shingles (herpes zoster).

Standard gabapentin dosage for adults: 300 to 600 mg taken three times per day by mouth.

Maximum gabapentin dosage for adults: 1800 mg daily in three divided doses.

Renally impaired patients (kidney disease): See dosage for renal impaired patients above

Gabapentin dosage for neuropathic pain

Gabapentin is most frequently prescribed off-label to treat nerve pain (neuralgia) due to nerve damage (neuropathy), compression, or irritation.

Standard gabapentin dosage for adults: 300 to 1200 mg taken three times per day by mouth.

Maximum gabapentin dosage for adults: 3600 mg daily in three divided doses.

Renally impaired patients (kidney disease): See dosage for renal impaired patients above

Gabapentin dosage for fibromyalgia

Gabapentin is used off-label to reduce fatigue, provide pain relief, and improve sleep in patients with fibromyalgia.

Standard gabapentin dosage for adults: 600 mg twice daily and 1200 mg at bedtime.

Maximum gabapentin dosage for adults: 2400 mg daily.

Renally impaired patients (kidney disease): See dosage for renal impaired patients above

Gabapentin dosage for alcohol dependence

Gabapentin is widely used off-label to reduce insomnia and cravings in people with alcohol use disorder, particularly those in the maintenance phase of alcohol abstinence.

Standard gabapentin dosage for adults: 300 to 600 mg taken three times per day by mouth.

Maximum gabapentin dosage for adults: 1800 mg daily in three divided doses.

Renally impaired patients (kidney disease): See dosage for renal impaired patients above

Gabapentin dosage for pets

You should not give gabapentin to animals unless a veterinarian has given the animal a prescription for gabapentin. Veterinarians frequently prescribe gabapentin to treat seizures or chronic nerve pain in pets and large animals. The recommended dose is 5-10 mg per kilogram of body weight (2.3-4.5 mg/lb) every 12 hours, but dosing will vary between veterinarians. Gabapentin dosages can vary from 3 to 11 mg per kilogram (1.4 to 5 mg per pound) as an analgesic to 10 to 30 mg mg per kilogram (4.5 to 13.6 per pound) as an anticonvulsant. As with people, the dose may start small and steadily increase until an effective dose is reached.

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.

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.