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.
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.
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.
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
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.
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.
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.
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.
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.
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.
> 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.
> 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. ..."
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.
20 comments
[ 2.7 ms ] story [ 45.3 ms ] threadThen 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.
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
https://chatgpt.com/share/68709753-d2ec-8010-ba8b-e7b57d610e...
TLDR:
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.
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.cell.com/cell/fulltext/S0092-8674(09)01185-4