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New Concerns About Gabapentin and Pregabalin (Lyrica) for Nerve Pain

Over 10 million people take GABA agonists for nerve pain. A recent report raises new concerns about gabapentin and pregabalin. What are the pros and cons?
Bottle of Gabapentin Pills

A recent review of the FDA’s Adverse Event Reporting System (FAERS) reveals some disconcerting data about commonly prescribed drugs for nerve pain (ISMP QuarterWatch Reports (March 27, 2019). This independent publication provides insights on emerging drug risks based on information submitted to the Food and Drug Administration. GABA agonists like gabapentin (Neurontin) and pregabalin (Lyrica) are prescribed primarily for neuropathic (nerve) pain. Lyrica is also prescribed for fibromyalgia. The latest ISMP report raises safety concerns about gabapentin and pregabalin that deserve some careful consideration by physicians, patients and FDA safety officers. 

Gabapentin and Pregabalin and the Brain

No doubt you have heard of the neurotransmitter called serotonin. One of the most widely prescribed antidepressants, fluoxetine (Prozac), became a household name because it was a selective serotonin re-uptake inhibitor (SSRI).

You have probably read about dopamine. It has been described as the “feel-good” neurotransmitter. Think of it as the reward neurochemical. If you experience something wonderful, the pleasurable feelings are probably impacted by dopamine.

Have you ever heard of a neurotransmitter called GABA (gamma-aminobutyric acid)? We didn’t think so. Whereas most neurotransmitters stimulate neurons, GABA is more like a brake on the brain. Neuroscientists refer to this as an inhibitory action. Not surprisingly, drugs that “calm” the brain often attach themselves to GABA receptors and/or enhance the activity of GABA. Think booze, barbiturates, benzodiazepines such as diazepam (Valium) or even sleeping pills like zolpidem (Ambien).

Gabapentin and pregabalin (Lyrica) are considered GABA analogs or gabapentinoids. In addition to being prescribed for nerve pain, they sometimes are used to treat “partial onset seizures.” You get the picture: brain brakes for epilepsy or sensations of pain.

Why Are GABA Drug Prescriptions Skyrocketing?

Prescriptions for these powerful brain modulating meds are way up. An article in JAMA Internal Medicine (Feb. 2018) notes that:

“The use of gabapentinoids more than tripled between 2002 and 2015.”

According to our calculations, over 10 million Americans are now taking either gabapentin or pregabalin. That represents more than 50 million prescriptions annually!

We suspect that many physicians have become worried about prescribing opioids to patients suffering from chronic pain. They have either reduced the dose of opioids and added a drug like gabapentin or substituted a GABA analog entirely for the more powerful pain relievers. That’s not just our opinion. An article published in the New England Journal of Medicine (Aug. 3, 2017) stated: 

“We believe, however, that gabapentinoids are being prescribed excessively — partly in response to the opioid epidemic…Patients who are in pain deserve empathy, understanding, time, and attention. We believe some of them may benefit from a therapeutic trial of gabapentin or pregabalin for off-label indications, and we support robust efforts to limit opioid prescribing. Nevertheless, clinicians shouldn’t assume that gabapentinoids are an effective approach for most pain syndromes or a routinely appropriate substitute for opioids.”

The report from the March 27, 2019 ISMP QuarterWatch reveals: 

“Gabapentin is so widely used that it is reported taken by more adults than any other psychoactive drug except the opioid combination acetaminophen/hydrocodone (Vicodin). It is so widely abused that a study of overdose deaths showed 32% had included it in a cocktail of lethal drugs that mostly included potent opioids.”

You can read more about the rise in gabapentin and pregabalin prescriptions at this link.

Are Doctors Overprescribing Gabapentin and Pregabalin (Lyrica) for Pain?

Why Are There Concerns About Gabapentin and Pregabalin?

The latest analysis from the ISMP QuarterWatch reveals some disconcerting data:

• “Risky polypharmacy. Nearly one-half of GABA analog patients were also taking 10 or more other drugs, increasing the risk of interactions, overdose, or inhibiting effects on other needed drugs.

• “CNS depression and overdose. 35% were also sustained users of opioids; another 18% were regularly taking an additional drug that activated GABA receptors such as alprazolam (Xanax) and zolpidem (Ambien).

• “Untested psychiatric combinations. 44% of GABA analog drug patients were also in sustained use of various antidepressant drugs. This suggests that doctors observing poor responses to antidepressant drugs were adding GABA analog drugs in untested and unapproved combination therapy.”

Are There Concerns About Gabapentin and Pregabalin Dependence?

The QuarterWatch also notes that:

• “Withdrawal symptoms/dependence. More than 1,200 reports described withdrawal syndromes, drug abuse, intentional misuse, or overdose.

• Mental impairment. Patients complained of memory loss, memory impairment, confusion, dizziness, and falls.”

We suspect that many health professionals are unaware of concerns about gabapentin and pregabalin dependence. They assume that such drugs can be discontinued at any time without problems. That is not what we are hearing from visitors to this website.

Ivy was not told she would need to wean herself off gabapentin slowly:

“I have taken 3600mg/day of Neurontin (gabapentin) for about 15 years for small and large fiber neuropathy and other neuropathic pain all caused by Lyme disease. I never had any side effects…in fact, I tell people gabapentin has no side effects!

“The only problem I had was when a doctor told me to stop taking it and to take GABA supplements instead because they are the same thing. They are not. I had withdrawal symptoms that made me feel like I was going insane. I cried all the time, etc. I’m surprised I didn’t have seizures. I didn’t realize why it was happening but went back on the gabapentin…and they went away.”

Jay wasn’t warned about a discontinuation syndrome:

“I was prescribed gabapentin after lower back surgery. Not sure it helped with the nerve pain. I developed a canker sore on my lip after a couple weeks. I also experienced night sweats (and unusual body odor).

“The doctor didn’t say anything about side effects upon stopping gabapentin suddenly. I found out what they were when I ran out and didn’t refill–anxiety, insomnia, feeling ‘crazy.’ It’s been 5 days and I finally got a decent night’s sleep. Even with the withdrawal symptoms I’m not going back on gabapentin!”

Judy had problems with Lyrica (pregabalin):

“I am currently tapering Lyrica from 225 mg daily to 200 mg. It has been almost a month. I have been on Lyrica for 15 months. I suffer from severe chest and spinal pain due to a rare condition. The nerve pain has returned with a vengeance, but I am determined to taper to 150 mg daily. The brain fog, lack of concentration, drowsiness, etc. was ruining my life. Withdrawal has been a nightmare.”

Side Effects of GABA Analogs:

Gabapentin can cause symptoms of depression, drowsiness, dizziness, fatigue, brain fog, balance problems and visual difficulties. Patients should be warned about the possibility of suicidal thoughts. If such occur, people should contact the prescriber immediately.

Pregabalin can also lead to cognitive difficulties, unsteadiness and dizziness. Some people develop coordination problems, fatigue, confusion, blurred vision, fluid buildup (edema) and dry mouth. If depression or suicidal thoughts occur, the prescribing physician should be notified immediately!

You can learn more about the side effects of GABA analogs at this link. There are over 800 comments so you can read about the experiences of many other patients.

Surprising Gabapentin Side Effects

Some People Get Relief from Nerve Pain:

We do not want to paint a grim picture about gabapentinoids. We hear from many people that concerns about gabapentin and pregabalin are overblown and that such drugs do help relieve nerve pain. Here are just a few examples:

Gin in Granby, Connecticut, reports positive results:

“Tingling and numbness are relieved with gabapentin. I am not depressed taking it. Rather I am thrilled to not have to experience neuropathy. I don’t have any side effects to speak of. If I do, they are minimal.”

Janet in Virginia is also a fan of gabapentin:

“It took two years to finally get a diagnosis of peripheral neuropathy in my feet that has come up my legs. I’ve been on Neurontin (now gabapentin) for over 25 years. That medicine has helped me live!

“Early mornings are bad until 8:30 when the pills kick in. I was also put on tramadol. These meds have allowed me to get around, even drive some. Yes, I am sleepy and off balance but these side effects are worth it.”

Lyn reports that gabapentin helps her:

“I have very debilitating polyneuropathy. I have been on gabapentin for about 8 years. It does help with the pain in my feet. I have bad loss of balance, fuzzy head and have fallen twice. People with neuropathy will take and do anything to relieve the jabbing, burning pains. Gabapentin is the only help I have found. I have tried everything, except Marijuana.”

Final Concerns About Gabapentin and Pregabalin:

We suspect that there is a lot of off-label prescribing of gabapentin. That may stem in part from the aggressive marketing of Neurontin for which the company was fined a huge amount of money. You can learn about this sad saga in the history of gabapentin at this link:

Gabapentin for Pain Drove Patient to Brink of Suicide

We agree with the conclusions of Quarter Watch:

“Substantial action is needed to reduce inappropriate use of GABA analog drugs… Further, treatment guidelines are needed to discourage incidental off-label use without careful monitoring and patient assessment. Other risks—notably possible harmful effects of long-term use—have not been adequately assessed in drugs almost exclusively tested in short-term trials. With the exception of opioid misuse, it would be hard to find a drug safety issue today affecting so many million adults where neither risks nor benefits have been adequately established.”

Reader Response, Please:

Share your own experience with gabapentin or pregabalin in the comment section below. You can read the full FREE report from ISMP’s QuarterWatch at this link.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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  • "Gabapentinoid Use in the United States 2002 Through 2015," JAMA Internal Medicine, Feb. 2018, doi:10.1001/jamainternmed.2017.7856
  • "Gabapentin and Pregabalin for Pain — Is Increased Prescribing a Cause for Concern?" New England Journal of Medicine, Aug. 3, 2017, DOI: 10.1056/NEJMp1704633
  • "Focus on 3 Psychoactive Drugs," ISMP QuarterWatch, March 27, 2019.
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comments (24 total)
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Lyrica 75mg twice a day has made me fatigued and sleep more than I used to.only on for 8weeks…notice hair coming out. Going to doctor tomorrow and will ask for lower dose

Have spinal stinosis and has stopped all the pain

I am on a 1000 mg of gabapentin for severe nerve pain. I only take an occasional pain pill now. The gabapentin has relived the debilitating pain in my legs. The worst side effect has been drowsiness which seems to be going away.

I had been taking gabapentin since 2010 to relieve symptoms of severe nerve pain following a microdiscectomy during which the surgeon tore the dura (the membrane surrounding the spinal cord).

I had taken as much as 2700 mg. per day, and for 8 of those years I was also taking morphine and hydrocodone. A year ago I graduated from the Mayo Clinic’s 3-week “Pain Rehabilitation Program” and am now off of: morphine, hydrocodone, xanax, clonazepam and methylphenidate.
Last month I returned to Mayo’s Pain Clinic and received a recommendation for Lyrica, starting at 150 mg per day and titrating up to 600 mg per day. I am currently at 400 mg per day. I find the Lyrica is more effective at controlling my pain. That said, I also am experiencing cognitive deficits: short-term memory impairments and with longer term memories I find I can remember images, e.g., people’s faces and images from movies, but I cannot retrieve the NAME of the person or the movie. Very strange experience. The other night “Tooty Fruity” was on the jukebox and I could see Little Richard’s face but couldn’t remember his name. This kind of thing keeps happening; picture is there but word isn’t.

On a different note. Regarding Balance Issues caused by Neuropathy, do you see anything on the horizon that can help us with this type of Neuropathy?

What is the difference between these prescription drugs and over-the-counter GABA supplements? A couple of the comments would indicate there are significant differences; I would like more information.

I was recently told I am not a candidate for HRT in spite of early menopause symptoms that are severe. Instead of hormones, the OB/GYN stated I should take Neurontin, which I disagreed with vehemently. Are there studies supporting the reduction of vasovagal symptoms with Neurontin? Yes. Does it provide relief for some according to these studies? Yes. So would Valium or Xanax and nobody would think about making that a first line treatment for menopause. I took Neurontin for a week when I had shingles and experienced discontinuation symptoms that were severe in spite of tapering myself off. As a therapist, I see a lot of substance abuse clients who take Neurontin in combination with other drugs.

I have been taking a low dose of gabapentin (200mg) at bedtime for several years because a sleep study confirmed that I was waking up many times a night, meaning that I would get up in the morning and feel like I did not sleep at all. This was to replace the clonazepam I took for several years for this problem, because I was getting scared about reports of that drug contributing to dementia.

I follow all of the standard advice about getting a good night’s sleep, but none of that prevents these frequent wakenings. Whenever I forget to take the gabapentin I wake up at least hourly all night long and feel horrible the next day. I hope that at this low dose it is safer than one of the “z” drugs. Besides, lack of sleep also degrades one’s memory, mental sharpness and overall health, so what’s a person to do?

Almost four yeats ago I was suffering from right sided low back and sciatica. Found out I had right sided synovial cyst! Was the largest neurosurgeon had ever removed. Surgery went well. Followed up with physical therapy. Unfortunately left with pain. Bottom line after two years on different pain meds which made me loopy I was placed on Gabapentin 600mg three times a day to total 2400 mg.
Eventually weaned myself off. Need to take 300 mg only once daily as needed. It’s a godsend! Side effects weight gain and constipaton.

While I was in the hospital recovering from lower back surgery I was prescribed gabapentin for leg pain. Soon after taking it my blood pressure rose. I asked the nurse if it could be from the gabapentin. She looked it up on her phone and it was a side effect. I stopped taking it and my blood pressure went back to normal

I have taken gabapentin since 2008. It is true that abruptly stopping The medication is harmful, may cause seizures, this is clearly stated in the patient pamphlet. However the risk of falls in my opinion is due mostly to the perpherial neuropathy. The foot/leg and the nerves supplying the leg for ambulation are not functioning properly, and the person is looking down to see where the feet are. This then makes the person more apt to fall first by gravity pulling downward, and second by poor perception of the nerves to make the balance adjustments. This seems like another way to just increase the suffering of chronic pain patients, by taking away what little relief we are able to find. If you don’t need it you will know, if you need it you will know. There is nothing like being eaten alive from your toes on up by fire ants.

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