Category: Gabapentin

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.1 In 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.

Gabapentin Dosage Forms

Neurontin (gabapentin) capsules and tablets are supplied as follows:

100-mg capsules:

Hard gelatin CONI-SNAP® capsules with white opaque body and cap printed with “PD” on one side and “Neurontin /100 mg” on the other. -bottles of 100 capsules

300-mg capsules:

Hard gelatin CONI-SNAP® capsules with yellow opaque body and cap printed with “PD” on one side and “Neurontin /300 mg” on the other. -bottles of 100 capsules

400-mg capsules:

Hard gelatin CONI-SNAP® capsules with orange opaque body and cap printed with “PD” on one side and “Neurontin /400 mg” on the other. -bottles of 100 capsules

600 mg tablets:

White, elliptical, biconvex, film-coated tablet with bisecting score on both sides and debossed with “NT” and “16” on one side. -bottles of 100 tablets

800 mg tablets:

White, elliptical biconvex, film-coated tablet with bisecting score on both sides and debossed “NT” and “26” on one side. -bottles of 100 tablets

Capsules contain : gabapentin, lactose, corn starch, and talc, Capsule shells may contain : gelatin, titanium dioxide, silicon dioxide, sodium lauryl sulfate, yellow iron oxide, red iron oxide, and FD&C Blue No. 2.

Tablets contain : gabapentin, poloxamer 407 NF, copolyvidone, corn starch, magnesium stearate, hydroxypropylcellulose, talc and candelilla wax.

What Medicines Are Good for Treating Headaches ?

When headache pain has you in its grip, a fast-acting headache remedy is a top priority. Some headache remedies come in the form of medication. But there are also many ways to achieve natural headache relief. Feeling better may require a combination of treatments.

Medications

Headache remedies for migraine headaches are usually prescription drugs, such as:

    • beta blockers: atenolol (Tenormin); bisoprolol (Zebeta)
    • tricyclics: amitriptyline (Elavil, Endep); doxepin (Adapin, Sinequan)
    • calcium-channel blockers: verapamil (Calan, Isoptin, Verelan)
    • anticonvulsants: divalproex (Depakote); gabapentin (Neurontin); topimirate (Topamax)
    • triptans: almotriptan (Axert); eletriptan (Relpax); sumatriptan (Imitrex).

Triptans are meant for acute treatment of migraines, while all the other categories are meant for chronic prevention of migraines.

You must talk to a doctor in order to get a prescription. The drugs are not available over the counter.

While there are also prescription medications for other types of headaches, such as tension headaches or sinus headaches, over-the-counter (OTC) headache remedies may be enough to relieve the pain they bring. OTC pills are available without a prescription, but as the Harvard Medical School Special Health Report Headaches: Relieving and preventing migraines and other headaches notes, they are medications and must be used carefully.

  • Acetaminophen (Tylenol and others) is a generally safe non-aspirin headache remedy. But doses above 3 grams per day, especially when combined with alcohol, can cause potentially fatal liver damage. If you consume three or more alcoholic drinks a day, every day, don’t take acetaminophen.

  • Aspirin quells pain and may prevent migraine headaches in some people when taken regularly. Long-term side effects include kidney damage and gastrointestinal problems, such as stomach pain, heartburn, or nausea. Bleeding from the stomach can also occur, often in such minute quantities as to go unnoticed. However, over time anemia may result, causing fatigue— which, in turn, may increase the frequency of headaches. Avoid aspirin if you have reflux, gastritis, or ulcers.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin, ibuprofen (Advil, Motrin, others), naproxen sodium (Aleve, Anaprox), and ketoprofen (Actron, Orudis, others). In some people, NSAIDs help prevent migraine headaches. Their long-term side effects are similar to those for aspirin.

Most healthy people who have mild to moderately painful headaches once in a while can take OTC headache remedies. But if you need to take an OTC painkiller several times a week, you should see your doctor.

Natural Headache Relief

Some people feel more comfortable seeking natural headache relief, in the form of plant-based or mineral supplements. Some of the most widely used preparations include:

      • Butterbur, an herb derived from plants in the genus Petasites
      • Feverfew, A daisy-like flower native to Europe
      • Peppermint oil, a culinary herb
      • Magnesium, a mineral
      • Coenzyme Q10 , an enzyme found in mitochondria, the energy factories of our cells
      • Vitamin B12

Consult your doctor before taking any of these supplements, as they can interact with medications to treat headaches or other conditions. The FDA does not regulate the effectiveness or safety of these products.

Activities that help

You may need more than just a pill for a headache remedy. Certain activities are also effective at relieving pain. For example, half of all headache sufferers in the United States use some type of mind-body technique to alleviate the pain. These include:

      • meditation
      • relaxation techniques, such as deep breathing
      • yoga
      • hypnosis, a state of deep relaxation that is similar to being in a trance
      • stress management

These mind-body therapies can help lower stress, a widely accepted headache trigger, and they also promote healthier lifestyle habits, such as getting adequate sleep, to keep headaches at bay.

Exercise, if performed regularly, is another natural headache remedy. It helps keep the heart and blood vessels healthy. It also boosts your mood, relieves stress, and helps prevent a host of ailments, such as high blood pressure.

Other natural headache relief

If your own natural headache remedies aren’t effective, consider alternatives, such as:

    1. Acupuncture: According to traditional Chinese beliefs, acupuncture works by affecting the flow of energy through pathways that run through the body.
    2. Psychotherapy: This can help you manage the effects that headaches have on your life, as well as the stresses and anxieties that may aggravate your pain.
    3. Physical therapy: This can provide relief for tension headaches and migraines by relaxing the tense muscles that commonly accompany tension and migraine headaches.

Seeking professional help

If headaches occur on a regular basis, it’s important to speak to your doctor, to see if an underlying condition is to blame, such as a medication side effect or a blood vessel abnormality.

Start with your primary care physician. You may be referred to a neurologist, who might order tests based on your symptoms. Once you have a diagnosis of the causes of your headaches, your doctor will be able to help you devise strategies for effective headache remedies.

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.

The off-lable use of Gabapentin for migraine

Gabapentin is as an anti-epileptic drug and as an analgesic, particularly for pain of the neuropathic or neurogenic type.  When used for controlling epilepsy, it is usually used in conjunction with another anti-epileptic drug.  But Gabapentin is widely used  to treat nerve pain or neuropathic pain than it is to treat epilepsy.

Gabapentin is also sometimes used to relieve the pain of diabetic neuropathy (numbness or tingling due to nerve damage in people who have diabetes), and to treat and prevent hot flashes (sudden strong feelings of heat and sweating) in women who are being treated for breast cancer or who have experienced menopause (”change of life”, the end of monthly menstrual periods). Talk to your doctor about the risks of using this medication for your condition.

It is also widely used to treat Anxiety and Migraine prevention.

One of Gabapentin “off-label” usage is for migraine prevention and treatment, including migraines with or without aura, vestibular migraines. It can reduce the frequency of headaches, pain intensity, and the use of symptomatic medications. Gabapentin is a good preventive therapy for migraines refractory to standard medications.

The chemical structure of gabapentin is related that of gamma-aminobutyric acid (GABA) which is a neurotransmitter in the brain. The exact mechanism as to how gabapentin controls epilepsy and relieves pain is unknown, but it probably acts like the neurotransmitter GABA.

The effective dose of gabapentin varies greatly. Some persons need only 200-300 mg a day whereas others may need 3000 mg or more a day. It may take several weeks to become effective, so it is important to stay on it for an adequate length of time.

The Efficacy of gabapentin in migraine prophylaxis experiment shows  gabapentin is an effective prophylactic agent for patients with migraine.

In the Clinical trials, 143 patients evaluated gabapentin for migraine prophylaxis.  After 3 months the patients taking gabapentin had a reduction of the migraine frequency by 1.5 migraines per month (or by 35.7%) compared with a reduction of 0.6 migraines per month for the placebo group. Also, gabapentin reduced the headache frequency by 50% or greater in 45% patients compared with only 16% patients on placebo. The most frequently reported adverse events  were asthenia, dizziness, somnolence, and infection.

In Famous medical websites, migraine patients also review the gabapentin as the migraine prevention medicine. They rate Gabapentin 8.1 stars out of ten stars. It is a high mark and means Gabapentin is a very effective medicine for migraine prevention.

I haven’t been taking this medication for long but it’s helped so much. Neuro started me off on 300mg at night and now I’m at 600mg at night. It doesn’t make me sleepy or drowsy. Before starting gabapentin, I was having migraines just about every day. I started having aphasia and vision changes with my migraines, so I decided to take action. I’ve only been on it for almost 2 weeks but I’ve been migraine free and my triggers are no longer triggers at this point, which is fantastic. I should note it has reduced my appetite but this is not a negative thing.” –  Crystaldreams July 25, 2017

This medication is..interesting. I am 20 with what a few doctors think is Fibro and a chronic pain condition but was Rx’d this med by a psych doctor for tension migraines. While it does NOT really help with migraines, it has been making me awfully sleepy and drowsy, and helping with weird aches and pains throughout my body. It can be used as a mood stabilizer and I can see why- because it makes you so drowsy you can’t do or say anything, especially after taking the evening dose! I’ve been afraid to drive any car since starting this. It makes me more drowsy than my anxiety meds which don’t make me drowsy at all! Doctor is raising the dose because since writing that first part- I have become quite used to the med, where my dose does NOT work  – Chelseabergstresser (taken for 1 to 6 months) May 11, 2017

“I have chronic Migraine called Glutamate Storm. First dose of 100mgs made me sleep 36 hours. Before I got the prescription I never slept more than 5 hours per night and often only got 2 hours of sleep per night. But I did not want to take a prescription every day, so I only took it when my ears were ringing really loud and I was sleep deprived. But then I noticed that my chronic cough was always gone the day after taking Gabapentin. So I started taking it every day for that. When I did, my headache and ear ringing got a lot better. I am now taking 400 mgs per day. I had bad breath at first, but it’s gone. Dr. says it might have detoxed something. I am all for that. Better out than in. This drug has helped me a lot. And I am not pro-pharma.” – Gylm April 26, 2017

Withdrawal Symptoms From Gabapentin

It is rare to experience withdrawal symptoms from gabapentin, but it does happen. A review of medical journals published between 1993, when gabapentin was approved, and 2015, found 18 case reports of gabapentin addiction, dependence, or withdrawal.

Doctors publish case reports when they encounter a patient with a rare disorder or with a condition that they want to make their colleagues aware of. Case reports are significant because they help further knowledge and identify subjects worthy of future research.

It’s worth noting that just because there are so few reports of gabapentin withdrawal, doesn’t necessarily mean it’s as rare as people once thought. It’s possible that many people simply don’t seek treatment for gabapentin withdrawal.

According to the Drug Enforcement Administration (DEA), gabapentin use is on the rise. Doctors wrote more than double the amount of gabapentin prescriptions in 2017 as they did in 2011.

The illicit use of gabapentin also appears to be increasing.

In a small survey of prescription drug abusers in Appalachian Kentucky, 15 percent reported using gabapentin to get high. That number is a 165 percent increase from the year prior and a 2,950 percent increase from 2008.

It appears as though gabapentin dependence and withdrawal are most common among people who use at least one other substance, such as opioids or alcohol. In the case reports, all patients had past drug or alcohol addiction issues.

Opioid users have reported using gabapentin to intensify their high. Cocaine users have reported the same, as well as attempts to use gabapentin to help alleviate cocaine withdrawal.

Signs and Symptoms

Among the documented cases, gabapentin withdrawal began between 12 hours and 7 days after the last dose.

The majority saw withdrawal symptoms within 24 to 48 hours.

Common Symptoms

The most common symptom was agitation, occurring in about half of the recorded cases. Confusion and disorientation were the next most common symptoms, followed by:

      • Sweating
      • Gastrointestinal symptoms
      • Tremors
      • Fast heart rate
      • High blood pressure
      • Insomnia

In many of the cases reported in the medical journals, individuals entered gabapentin withdrawal without the intention to do so.

This was typically a result of running out of gabapentin or leaving it at home during a trip out of town.

This sample of cases is unlikely to be reflective of most people’s experiences with gabapentin withdrawal. The reason for this is that only people with severe or alarming symptoms seek emergency medical treatment.

Among the cases reported, gabapentin withdrawal symptoms typically peaked three days after someone’s last dose. In almost all cases, doctors eventually treated the symptoms by resuming the previous gabapentin dose. Once people resumed their dose, their symptoms disappeared within hours.

Gabapentin Comes With Serious Risks if you Don’t Take it as Prescribed

Gabapentin oral capsule is used for short-term or long-term treatment.

The length of treatment depends on what condition it’s being used to treat. It comes with serious risks if you don’t take it as prescribed.

If you stop taking it suddenly or don’t take it at all:

    • For seizures: This can increase your risk of status epilepticus, which is a medical emergency. With this condition, short or long seizures occur for 30 minutes or more. If your doctor decides to reduce your dose or have you stop taking gabapentin, they will do this slowly. Your dose will be reduced or your treatment stopped over the course of at least one week.
    • For postherpetic neuralgia: Your symptoms won’t improve.

If you miss doses or don’t take it on schedule: Your medication may not work as well or may stop working completely. In order for this drug to work well, a certain amount needs to be in your body at all times.

If you take too much: You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include:

      • double vision
      • slurred speech
      • tiredness
      • loose stools

If you think you’ve taken too much of this drug, call your doctor or local poison control center. If your symptoms are severe, call 911 or go to the nearest emergency room right away.

What to do if you miss a dose: If you forget to take your dose, take it as soon as you remember. If you remember just a few hours before the time for your next dose, then only take one dose. Never try to catch up by taking two capsules at once. This could result in dangerous side effects.

How to tell if the drug is working: You should have fewer seizures. Or you should have less nerve pain.

Neurontin, Gralise, Horizant (Gabapentin) and Lyrica, Lyrica CR (pregabalin): Serious Breathing Problems

TOPIC: Neurontin, Gralise, Horizant (gabapentin) and Lyrica, Lyrica CR (pregabalin): Serious Breathing Problems

AUDIENCE: Patient, Neurology, Pain Management, Pulmonology, Pharmacy

BACKGROUND: Gabapentin and pregabalin are FDA-approved for a variety of conditions, including seizures, nerve pain, and restless legs syndrome.

ISSUE:FDA is warning that serious breathing difficulties may occur in patients using gabapentin (Neurontin, Gralise, Horizant) or pregabalin (Lyrica, Lyrica CR) who have respiratory risk factors. These include the use of opioid pain medicines and other drugs that depress the central nervous system, and conditions such as chronic obstructive pulmonary disease that reduce lung function. The elderly are also at higher risk.

FDA is requiring new warnings about the risk of respiratory depression to be added to the prescribing information of the gabapentinoids. FDA has also required the drug manufacturers to conduct clinical trials to further evaluate their abuse potential, particularly in combination with opioids, because misuse and abuse of these products together is increasing, and co-use may increase the risk of respiratory depression.

RECOMMENDATION: Patients and caregivers should seek medical attention immediately if you or someone you are caring for experiences symptoms of respiratory problems, because these can be life-threatening. Symptoms to watch for include:

  • Confusion or disorientation
  • Unusual dizziness or lightheadedness
  • Extreme sleepiness or lethargy
  • Slowed, shallow, or difficult breathing
  • Unresponsiveness, which means a person doesn’t answer or react normally or you can’t wake them up
  • Bluish-colored or tinted skin, especially on the lips, fingers, and toes

Always inform your health care professional about all the drugs you are taking, including prescription and over-the-counter medicines and other substances such as alcohol.

Health care professionals should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when co-prescribing gabapentinoids with an opioid or other central nervous system depressant such as a benzodiazepine.

For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.

Gabapentin Can be Used to Treat Anxiety and Depression

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
Gabapentin

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.

Gabapentin in the Treatment of Anxiety and Depression

Gabapentin is rarely prescribed for patients with only anxiety disorder but is commonly prescribed for patients with bipolar disorder to reduce anxiety levels. Clinicians can also use it for patients who have anxiety and depression. Since anxiety is a coping skill, there is no drug to treat anxiety, but the medications used for this purpose make it possible to live at the moment, giving patients a chance to undergo anxiety treatment with non-pharmaceuticals. Even though the studies show that gabapentin is ineffective in the treatment of bipolar disorder, a case-control study with 60 patients in an acute phase of mania had a significant reduction in symptoms of anxiety with lithium and 900 mg of gabapentin. In another study with 21, mixed-state patients refractory to mood stabilizers received gabapentin (up to 2000 mg per day) for eight weeks, and patients with depressive symptoms had significant improvement in their CGI-BP (Clinical Global Impression-Bipolar) scores.

A meta-analysis of 7 trials pointed to gabapentin’s greater efficacy versus placebo in generalized anxiety disorder (GAD), although the effect size was approximately 0.35 for mental anxiety symptoms. A study of 153 patients who responded to the initial treatment of 450 mg per day for maintenance treatment of social anxiety disorder.

There are no clinical studies on the effectiveness of gabapentin as monotherapy or adjunctive therapy in major depressive disorders. However, there are case reviews that show some patients with depression who are refractory to standard antidepressants but showed therapeutic improvement when using gabapentin as adjunctive therapy.

In a randomized, double-blind study, with 130 patients that had under eye surgery, a one-time dose of 600 mg gabapentin significantly reduced the perioperative anxiety compared to a placebo. However, there was no significant difference compared to melatonin.

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

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

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

Comparative Studies

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

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

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

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

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

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

(1) shortness of breath;

(2) dizziness, fatigue, and nausea;

(3) increased spasticity and pain;

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

(5) severe itching.

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