Nerve pain drug gabapentin linked to increased dementia, cognitive impairment | Hacker News Reader

Nerve pain drug gabapentin linked to increased dementia, cognitive impairment

medicalxpress.com

80 pointsclumsysmurf59 comments

Absolutely no causal link was shown. Maybe the nerve pains for which doctors prescribe gabapentin increase the risk of dementia on their own, or maybe there is some third factor that causes both nerve pain and dementia.

in this study it was linking prescriptions given for back pain

Not sure why this comment is getting downvoted. The article itself states that:

> "This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. The researchers also acknowledge that their study was retrospective, and they weren't able to account for dose or length of gabapentin use."

Not to be too meta, but it’s kind of boring to point out the obvious limitation of the research method.

“No casual link is proven” could be said about so much science, specifically medical science and other disciplines which limit research methods for ethical or practical constraints. So you end up with this comment in every front page post about an observational medical study. We could be discussing the actual research or its implications, instead of repeating a discussion on limitations of research methodology.

In addition, I find these types of critics to be a little too cynical even for my taste. There’s a whole group of people that feel smart by finding ways to dismiss scientific studies even when there is some actually interesting data being brought up.

On first brief reading I misunderstood the title to be causal, even though it only claims a link. I think it is worth pointing out for those who check the comments before reading.

Edit: clarity

Yes, these comments are necessary pushback against the habit of these disciplines to push interventions that don't work because their evidentiary standards are bad.

Valid comment. In general retrospective studies aren't that rigorous, yet researchers love them (usually a quick and easy publication). They aren't easy to do well because controlling for confounding factors isn't easy - even if you think you know what you need to control for, data often isn't available, and even then, how you control for it can drastically change your findings.

Then layer on top the available data. I assume in this study they just tried to create a control group and an intervention group based on gabapentin prescriptions, then tried to see how many had a dementia diagnosis. So many ways the data can mislead! Differences between the control and intervention group when it comes to total exposure to drug, other medical interventions, diagnosis rates, family history, etc, etc. They are basically going in blind.

Retrospective studies can be useful in identifying potential signals. It's what we do for drug safety regularly. But it's not rigorous enough data to start making changes to medical care - you need a more rigorous study to confirm.

But what annoys me is the coverage these studies get. The average reader thinks "oh my god!", when they should think "interesting, but there is a good chance they are seeing a signal that isn't there".

A great example of the impact is the use of hormone replacement in menopausal women. It used to be very common until a study came out showing higher rates of uterine cancer (I believe). Use of hormone replace went way down, plenty of women suffered from menopausal symptoms for a few decades.

Then a massive (160 women) prospective, randomized, controlled study (WHI) were done and it was clear the safety signal wasn't there.

I've taken quite a lot of these. I was on 3600mg/day for about 5 years. I was later on lyrica for about 3 years.

These drugs _do_ help you to tolerate nerve pain, but do _not_ stop it. I found they led to my otherwise amazing memory developing "holes" - I knew I knew something, but I couldn't put my finger on it. As someone accused of having an eidetic memory (I'm not convinced) I found this really disturbing. I also felt more stupid, and less quick.

I've been off gabapentinoid medications for about 4 years. My pain is more "in my face", but I no longer feel retarded.

Note: The advice on the gabapentinoid box "May increase the effects of alcohol" is both warning and recommendation. It's not unknown for the mix to include open-eyed hallucinations.

Holy! 3600mg is a lot-a lot.

GABA analogues are known to impact memory formation.

It’s the top end of what gets prescribed for spinal nerve pain but not an uncommon dose. I was on the same. I spent the last year tapering off of it.

I’ll note I did not have the same experience. It eliminated my nerve pain and I did feel mentally sluggish when I first started but that receded and I didn’t have memory issues while on it.

As far as you can remember.

When they say given 'x number of prescriptions of gabapentin', what does a prescription actually mean dosage and length wise?

I would love more info on this because I have been taking gabapentin for years due to nerve damage from having Guilliane-Barre syndrome.

Edit: Re-reading the article, i see 'The researchers also acknowledge that their study was retrospective, and they weren't able to account for dose or length of gabapentin use.' - this seems like a pretty gaping hole in trying to draw an kind of conclusion from this

I tried looking this up, and they don't say anywhere what they mean by prescription. Mine are 90 days, so I want to assume thats normal but don't honestly know. Looking up dosing it seems that 3x300mg is as small as is prescribed, and it can go up to 3x1200mg.

Then we have the increase in incidence. The incidence rate is already small in those age groups, so even doubling it is a tiny number.

I'm going to stop taking it (I take something between 1/10 and 1/5 of my prescribed dose anyhow) and think about if the benefit to me is worth the added risk.

I unfortunately don't really have the luxury of just stopping it - if I don't take it, the nerves in my hands and feet start to almost feel like they are 'buzzing', like constantly, randomly active.. which makes sleep practically impossible

Sorry to hear that. I'd say that risk very small absolute risk is worth it then, given both the quality of life and the other health problems that lack of sleep would bring.

I have worse version of that, when I feel any sensation as pain all over skin. Nothing helps much, so I got into opioid abuse.

Right now, fresh out of rehab, thinking about my options.

The widespread use of Gabapentin and Pregabalin to treat neuropathy is off-label their original function as anti-convulsant and anti-psychotic meds. In addition to the documented negative side effects, withdrawal by elderly patients from extended use can be difficult, even with months of tapering. They can negatively affect memory and cognition.

https://en.wikipedia.org/wiki/Gabapentin

> Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat neuropathic pain and also for partial seizures of epilepsy.. is [ONLY] moderately effective: about 30–40% of those given gabapentin for diabetic neuropathy or postherpetic neuralgia have a meaningful benefit.

Those with peripheral neuropathy should audit the total amount of Vitamin B6 in their diet and daily supplements. Try to keep the daily amount below 10mg. There have not yet been lawsuits to add bottle label warnings, but Australian regulators have issued a safety warning.

https://www.tga.gov.au/news/safety-alerts/health-supplements...

> Vitamin B6 (pyridoxine) is in lots of multivitamin and mineral supplements that can be bought in supermarkets, health food shops and pharmacies without a prescription. Many people are not aware that vitamin B6 can cause peripheral neuropathy, which results in tingling, burning or numbness usually in the hands and feet. Taking vitamin B6 even at low doses can cause peripheral neuropathy but people are more likely to get it if they are taking more than one supplement.

One of the known side effects of this drug is Suicidal Ideation.

My late wife was taking this crap when she killed herself; see the documentary Pain Warriors for that whole saga.

I've been warning people about this drug for years. One lady told me, months after a warning to her group: "Bob, I was standing on the railing of a bridge ready to jump, when I heard your voice. I got off of the bridge and got help."

This stuff really needs to be removed from the market. I acknowledge that I've been told by a very few that it helps them. I've been told by far more how it harmed them.

See also from the Journal Cell Oct 16 2009, relating to both Gabapentin and Lyrica, because other comments here are speculating about how it works:

"... α2δ-1 is the high-affinity receptor for two commonly prescribed antiepileptic, antineuropathic pain medications, gabapentin (GBP, Neurontin) and pregabalin (Lyrica) (Gee et al., 1996). GBP and pregabalin were initially designed as hydrophobic gamma amino butyric acid (GABA) analogs that could cross the blood-brain barrier. Further studies have shown that even though they posses anticonvulsant properties, they do not bind to GABA receptors or transporters. A recent study using a knockin mouse that expresses a mutant α2δ-1 that cannot bind GBP or pregabalin has shown that α2δ-1 is the in vivo target for these drugs and that these drugs mediate their therapeutic action through binding to α2δ-1 (Field et al., 2006). GBP and pregabalin do not affect the single-channel kinetics of calcium channels and have only modest effects on neurotransmission (Dooley et al., 2007). Thus, the cellular mechanisms underlying the mode of action of these drugs are unclear. ..."

https://www.cell.com/cell/fulltext/S0092-8674(09)01185-4

The smallest capsule of pregabalin/lyrica is 25mg. After reducing to that minimum, it still took months of further tapering by dividing capsules, before withdrawal symptoms ended in one elderly patient. Pregabalin suppresses nausea, which means nausea is a symptom of withdrawal, requiring ginger tablets or other anti-nausea assistance during tapering.

https://www.thetimes.com/uk/article/an-anxiety-drug-killed-m...

> An investigation by The Sunday Times has revealed that pregabalin has the fastest-rising death toll of any drug in the UK, based on figures compiled from official data across all regions. It is detected in a third of all drug-related deaths. In 2012, pregabalin was indicated in nine fatalities. A decade later, in 2022, the number had risen to 779, with almost 3,400 deaths in the past five years.

Yet sadly it is still on the market. Is there a number of deaths that are enough?

There is also this small 2016 study:

"Interference with neuronal development

Pregnancy outcome following maternal exposure to pregabalin may call for concern

ABSTRACT

Objective: To investigate pregnancy outcomes following maternal use of pregabalin.

Methods: This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to pregabalin with those of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs). Teratology Information Services systematically collected data between 2004 and 2013.

Results: Data were collected from 164 exposed pregnancies and 656 controls. A significantly higher major birth defect rate in the pregabalin group was observed after exclusion of chromosomal aberration syndromes, and when cases with exposure during first trimester of pregnancy were analyzed separately (7/116 [6.0%] vs 12/580 [2.1%]; odds ratio 3.0, 95% confidence interval 1.2–7.9, p = 0.03). The rate of live births was lower in the pregabalin group (71.9% vs 85.2%, p < 0.001), primarily due to a higher rate of both elective (9.8% vs 5.0%, p = 0.02) and medically indicated (5.5% vs 1.8%, p = 0.008) pregnancy terminations. In the Cox proportional cause specific hazards model, pregabalin exposure was not associated with a significantly higher risk of spontaneous abortion.

Conclusions: This study demonstrated a signal for increased risk of major birth defects after first trimester exposure to pregabalin. However, several limitations such as the small sample size, differences across groups in maternal conditions, and concomitant medication exposure exclude definitive conclusions, so these results call for confirmation through independent studies."

Still on the market...Why?

https://web.archive.org/web/20161029080541/https://www.neuro...

In theory, LLMs could review more sources for a personalized risk assessment. But a brief query on this subject yielded generic responses from multiple LLMs :(

I've seen AI recommended things like Fluoroquinolones (Avalox, Cipro, Levaquin etc), for UTIs.

The FDA itself says this class of drugs work no better than a placebo for UTIs, Sinusitis and Bronchitis. While they cause life altering side effects. They 'Flox' people.

My late wife's Journal was part of the evidence during a 2015 FDA hearing to get this crap off the market.

The bottom line is that AI can not be trusted for Medical Advice. Be highly suspicious of a Human doctor recommending a drug in this class, that has so many Black Box Warnings.

All antidepressants cause same, and evidence that they work is not awesome (they work barely better then placebo) The question is should the whole industry be destroyed, or what?

Very hard things to solve. Opioids help with pain, but destroy lives in the long term. Should they be almost never prescribed, except in severe pain and never longer then a week (except in hospice?)

More questions then answers

My mates on something for nerve pain, and he reckons its the worst thing in the world. Makes him vomit.

So he takes pills for nausea that make him extremely drowsy.

So then he takes uppers, which bring back the nerve pain.

Cool study, I will share it with him. But I get the impression that he would prefer to be demented than paralysed with never pain.

This is a hugely widely-prescribed drug, generally considered extraordinarily well tolerated, so whatever impact gabapentin has on dementia, the effect would have to be pretty small --- in particular: there's no spike that tracks the point at which it started become so widely prescribed.

This wouldn't necessarily be expected for the same reason that if one looked at new smokers after 10 years, there'd be no significant spike in lung cancer. This is what makes long terms effects of things so difficult to prove. Even tylenol/paracetomol is still having some interesting new discoveries made. This is the main reason I tend to strongly adhere to the precautionary principle when it comes to any sort of "new" drug.

It's been like 30 years. We'd see it, if there was a significant effect.

But we are? The article describes an extremely significant effect because dementia rates are already very high at, for instance, ~10% in the 70+ age group. So twice as likely to develop dementia is an extreme effect, as opposed to e.g. twice as likely for something that occurs at a rate of 1 in 10,000 or whatever.

The bigger question would be causality. Observational studies are generally trash, especially with dementia, because it correlates with practically everything in one way or the other. So is it the drug, or is there a common confounding variable among people who use the drug?

That's the problem that makes proving causality so hard for many drugs. Long-term effects are subject to practically endless possible confounders. Like the National Academy of Sciences is rather fond of saying, you end up with endless scenarios where there is neither enough evidence to accept nor reject a possible causality. People that want to spin things one way then claim there's no evidence, which is plainly false - as there is, but its insufficient to confidently claim causality. In the same way that there's insufficient evidence to reject causality.

What’s happening with Tylenol?

Search for '[acetaminophen/paracetamol/tylenol] study' every few years and you'll find something new. The latest seems to be strong observational evidence that it drives neurodevelopmental issues, including ADHD/autism, when taken during pregnancy. This is being pushed back against hard because this has led to Johnson & Johnson being sued by hundreds of people claiming they already knew this, setting them up to become the next big tobacco if they lose.

The link is very strong and so big pharam's defense is that it's not not tylenol, but having an issue for where tylenol might be needed, that is causing the issues. A bizarrely excellent and balanced article on the issue is available here. [1]

[1] - https://www.thetransmitter.org/spectrum/scientists-debate-ev...

I was gonna come down super hard on you, but I think you might be right. Jesus Christ.

https://pmc.ncbi.nlm.nih.gov/articles/PMC9385573/

Well damn. I take this as needed for a back injury that left me with chronic pain. My prescription is for a LOT more than I take (I take it about 20% as often as prescribed).

Now I'm not so sure I want to take it. My saving grace is that I'm on the younger end and haven't taken it that long.

After reading the paper and looking into dosing I learned that I'm taking a tiny fraction of the normal dose. Wow. Learn something every day.

It cured my cat's hyperesthesia so lil guy is gonna stay on it.

By "cured", you mean mitigated, right? Otherwise you would not need to keep administering it.

Of course

In causing dementia, there is not a more potent drug than topiramate (antiepileptic and migraine prophylaxis). Gabapentin is not so dangerous, in my experience (neurologist). Although all neurotropic drugs are suspicious for dementia, the effect size varies wildly.

As results are quantified by number of “prescriptions”, and 6 prescriptions of n pills at a given dosage presumably increase risk over 1 prescription of 6(n) pills, then they’ve clearly proven the risk factor is going to the pharmacy.

Also true for benzos. Basically messing with GABA system seems to do this.

The connection for benzos is somewhat tenuous in its own right, but gabapentin actually has basically nothing to do with Benzos and does not act on your GABA system

Okay, thank you, I assumed it worked on GABA due to it being named gabapentin and because of its potential for abuse. I've just always assumed that taking drugs that make you less smart acutely might indeed make you less smart over the long-term too. I've known people who would take Gabapentin for a minor high.

Gabapentin can lead to dissociative, intoxicated-like, sedentary-like, and confusion-like state. It also partially/theoretically impairs long term memory formation similar to Ambien. I bet OD also leads to hallucinations.

I believe gabapentin was once believed to be a positive allosteric modulator (PAM) on certain GABA, and now they don’t even believe that to be the case but it somehow affects GABA expression and activity indirectly. (It’s definitely not a GABA agonist.)

It is also not very potent but there is another drug that shares its mechanism that is potent in single digit mg amounts: pregabalin (Lyrica). It is potent and kinda sorta abusable (not really) and they both can produce a super mild but benzo-ish sedation for a couple hours for a day or two.

It is apparently a coincidence that the drug seemed to resemble GABA and got its name though. Strange.

~~[EDIT: sed s/.*//] -> Benzos are anticholinergic though. I don't see gabapentin listed as such.]~~

Wait what? Benzos are not anticholinergic in any sense of the word that I know of.

My bad, I'm smoking the proverbial crack. Benzodiazepine addiction => fucks up the GABA system. Anticholinergic, anti-dopaminergic, and GABAnergic breaks different delicate bits.

This might not be good. My mom takes a bunch of it for post-stroke syndrome/neuropathic pain. She reports taking too much feels like being tired/drunk.

eeep. We just gave this to our dog after knee surgery.

Gave to my cat when we flew. It was not pleasant mainly because it didn’t work.

I would give it to my dogs a couple times a year in anticipation of fireworks. It worked wonders in their case.

It work for cats, but not equally for all, some are less responsive. Also, maybe I will say obvious things, but - cats require bigger dose per kilo than dogs, vet doctor can calculate it for you; and it is advised that you start giving it to cat a day in advance.

A short course of the medication for post-surgical pain is unlikely to be a serious risk, either in humans or dogs. The patients in the study were taking the drug over a long period of time (months or years) for chronic pain.

Had it added to paroextine by a psych nurse after finishing a project for the boss from hell. Had the kind of diffuse chronic pain associated with depression and Kohut's "triple split" personality organization which I knew I had then but didn't know why

https://mastodon.social/@UP8/111687412198643478

Can't say gabapentin really helped with the pain but I sure slept well and...

I had terrible social anxiety earlier in my life but in this phase I was getting up every morning and calling people up and down the east coast first thing and working my way to the west coast with my BD guy, never sold anything but boy people told us a lot of things they shouldn't have told us (e.g. EADS was way over its head in a project for the NSA) and I can't go to my grave and say I didn't give a serious try for the idea I had.

Settled in a real job in a real office, doc said I should try quitting paroxetine. Wasn't hard at first but there was that day I got furious about the messes in the house and got 40,000 steps cleaning without going outside and that time I got a psychogenic fever and lost 15 pounds in 3 weeks and kept it off for a year. Then that guy in the upper left corner of that card went through a series of transformations like a character in an anime: first a cute little bunny, then an ugly thing the size of a large bear, then a giant robot maybe 30 feet tall, finally a Godzilla kind of creature maybe 300 feet tall. He posted plenty on HN using my account and made trouble for myself and other people until a crisis broke and I was like "WTF happened there?" and kinda retreated for a year until Lezengreber's book fell into my hand and revealed how I was different from other people (schizotaxia) and why I had that triple split.

If anything good came out of that time it was that I learned my chronic pain was due to TMJ and managed it and now my jaw bugs me maybe one day a month.

Quit smoking pot, had trouble sleeping, would get up in the morning and experience "paranoia towards objects" and have plates jump out my hands like a ouija board and bonk my head four times in a row getting something out of the fridge, it seemed like my wife was always trying to stand exactly where I was going to go next when I was getting ready in the morning. Presented really bad at my doc and got put on a tiny dose of quietapine at night. Helped with the sleep and had only one little bit of 'psychosis' since and been very easy to live with.

I've been worried about the long term effects of gabapentin so I have been backing off my dose. I'm worried about the quietapine too for that matter.

Got friends though who take benzodiazepines for anxiety and those look really dreadful. That really arrests your development, people like that will have the same conversation with you that they had 12 years ago and at least I am not like that.

I know someone who made it to 92 or so with dementia and he was a really nice guy who was totally confused but good natured and easy to live with. My worst fear is that I lose my compensation for my schizotypy (verbal IQ too high to measure really seems to help with that) when I get older and get really paranoid and mean so I do try to develop habits of benevolence but I don't have the deep practice that guy had.

Can say though that I have zero anxiety now I feel like I am an expression of a principle and, on a certain level, can't be defeated. Don't know how much is the meds and how much is maturity.

>it seemed like my wife was always trying to stand exactly where I was going to go next when I was getting ready in the morning

That one might have been real. All I had to do was pick up a pot of boiling water or turn around after taking a kitchen knife from the drawer and mine would teleport directly behind me.

Careful. It might drool all over, develop an unhealthy fascination with squirrels, or randomly forget its own name :D

Oh no! ...wait.

My dog is on this. I wonder if it affects canines?

our vet recently prefers to prescribe Pregabalin instead of gabapentin

This was already a scary drug. Was given it for back pain and looked up the side effects. No thanks.

Medical journalists are incentivized to make you concerned. I highly suggest all medical journalism be run through a good AI to be put into context.

https://chatgpt.com/share/68709753-d2ec-8010-ba8b-e7b57d610e...

TLDR:

  The paper offers an interesting signal that heavy gabapentin prescribing tracks with higher dementia/MCI diagnoses, especially in 35-64-year-olds.  Yet substantial unmeasured confounding, possible reverse causality, and modest absolute risk increments mean we’re far from proving gabapentin is neurotoxic.  It’s a reminder to prescribe purposefully, review regularly, and keep cognition on the monitoring checklist—but not a reason for abrupt discontinuation in patients who benefit.

Reply on news.ycombinator.com