> "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."
“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.
Edit: clarity
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.
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 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.
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
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.
Right now, fresh out of rehab, thinking about my options.
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.
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...
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.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.
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.
GABA analogues are known to impact memory formation.
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.
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.
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.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.
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...
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.
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
acomjean•7mo ago
moomoo11•7mo ago
mordechai9000•7mo ago
Yizahi•7mo ago
duskwuff•7mo ago
PaulHoule•7mo ago
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.
washadjeffmad•7mo ago
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.
sonofhans•7mo ago
ykonstant•7mo ago