1/
HOW does gabapentin work?
DOES gabapentin work?
WHY is gabapentin so shady?

Join me for a #tweetorial?

Keywords: Glutatmate, Asterixis, Alcohol-use disorder
#livertwitter #MedTwitter #meded
2/

Admitting a non- #cirrhosis patient with gabapentin overdose as an intern, I saw asterixis

This 🤯

If it caused asterixis (throwback: https://twitter.com/ebtapper/status/1293647872290938880?s=20), did that mean it causes HE?

Gabapentin has confused me ever since
3/
Everything about gabapentin is🍌
What follows is no different

There once was a💡dream💡 of using GABA signaling 2 prevent seizures. Yada yada yada, we made GABApentin. It approved in 1993!

Just one prob:
GABApentin doesnt bind GABA-receptors!

Like I said…🍌
4/

5 Gabapentin facts re: how it ⬆️🧠inhibitory tone

1⃣lipid soluble (crosses🩸/🧠barrier)
2⃣Binds voltage-gated Ca Channel
3⃣⬇️GABA & Glutamate release
(nb: Glu is excitatory)
4⃣Prob⬆️GABA concentration in🧠
5⃣⬆️Noradrenaline release, causing descending inhibition
5/

These gabapentin effects may reduce pain

So people prescribe it for pain... a lot

Problem number two...

The evidence for pain control is far from awesome
6/

Q: Why would people use so much gabapentin for pain when the evidence is lacking?

A: Pfizer systematically promoted off-label use, filling PubMed with biased results, burying negative studies. The FDA fined them $1 billion for this (& other issues)
7/

Suffice it to say, I have been suspicious of gabapentin for a long time. First the asterixis, then the shady marketing

We even found it was associated with incident hepatic encephalopathy! #cirrhosis
https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep4.1425#:~:text=Among%20166%2C192%20Medicare%20enrollees%20with,nonalcoholic%20fatty%20liver%20disease%20cirrhosis. #livertwitter
8/

I was done with gabapentin!

Then we found alcohol-related liver disease was becoming an epidemic, particularly of the young
We wanted 2 do more!

That's when my friend, Jessica "Dr. ALD" Mellinger said:

"Did you know GabaP can be used for alcohol-use disorder?"

🤯
9/

It turns out that the neurocognitive effects of alcohol may be largely mediated by glutamate signaling

Glutamate also has a huge role in reward pathway signals

What medication reduces glutamate signaling?

You guessed it...
10/

It turns out that if you put an alcoholic drink in front of someone with alcohol-use disorder, gabapentin reduces their cravings

It also turns out that gabapentin treats alcohol withdrawal symptoms
11/

In multiple RCTs, gabapentin has been shown to reduce the rate of risky drinking
12/

To review

1⃣Gabapentin ⬇️glutamate & GABA signaling without binding GABA receptors
2⃣Glutamate & GABA play a role in alcohol use disorder (AUD) & in etoh-withdrawal physiology
3⃣Gabapentin may be useful for AUD
4⃣That's cool. But gabapentin is still super shady
/end

This concludes a #tweetorial on gabapentin. I hope you enjoyed!
🙏Thank you for reading 🙏
It has been a rollercoaster of emotion and rapidly changing opinions for me as I have tried to understand this🍌drug🍌
You can follow @ebtapper.
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