Gabapentin possibly making depression worse

[paranoid android]

Im not quite sure if this is the right form for this or not so feel free to move it if it's not.

Ive noticed that gabapentin seems to worsen the depression aspect of my bipolar. I will be feeling perfectly fine alot of times until i take my first gabapentin dose of the day and i get thrown into a real lethargic depression or sometimes a mixed state.

I have sort of suspected this for a long time that it's making it worse somehow and ive read that it can cause mental and mood changes. But im not sure if this really happens alot or it's just a warning now because of the fact that the company who makes neurontin marketed it off label for treating bipolar disorder which lead to some suicides and lawsuits i believe. I think it's pretty much been proven that gabapentin is no good for bipolar at all.

I don't take it for bipolar disorder i take it for neuropathic pain. I take lamictal for my bipolar disorder and that seems to help alot even though i still do have my bad days. But i have noticed that my mood is better on the days that i don't take gabapentin and since im now on the fentanyl patch and thats helping the pain alot i was thinking of maybe dropping the gabapentin altogether.

Anyway my question is is there any evidence that gabapentin can actually cause or worsen depression in people that have bipolar or other mood disorders?

 

[Boiling in Acid]

i don't know it's the right answer to that, but iv'e read that increased GABA decreases serotonin & dopamine, & since gabapentin is a GABA analogue, maybe it relates...

 

[Adrenochrome]

i don't know it's the right answer to that, but iv'e read that increased GABA decreases serotonin & dopamine, & since gabapentin is a GABA analogue, maybe it relates...

Although I wouldn't doubt that it might do this in some parts of the brain;
I'm sure this is not what it does throughout the brain!

And different neurons in different parts of the brain (and there are many parts of the brain) do different transduce responces from the same ligands in different ways

eg, Dopamine is, throughout the brain, not solely an inhibatory transmittor, it's not solely an exitatory transmitter (this also applies to glutamate, seratonin, AND ALL OTHER CHEMICAL SINGALS IN YOUR BRAIN AND THE REST OF YOUR BODY)

in conclusion the cellular context matters the most!! and you deinately need to integrate that for the entire body (and you prob need some kind of degree in human biology to do so, even then)



To the original poster, have you ever heard of pragaballin(sp?), perhaps u should ask your Dr to try that one, though it may not be any better for you.

 

[Adrenochrome]

lol; sorry to go ape on you, I didn't realize your post wasn't an exclaimation and was just a stab at answering the question :/ so no offience intended my friend

(also i thought i was in other drug, where i can spout CAPS)

 

[Ham-milton]

I take Gabapentin for Bipolar as well, but unlike 99% of the population, 1500mg of the stuff gets me high as a kite. Not in a good "I'm enjoying the hell out of this" sort of way- more of a "I'm manic and vrooom" sort of way... If that makes any sense at all.

I still love the shit.

Anyway, though I haven't been taking it on a daily basis for a while (2-4 days a week), I much prefer it this way. I have taken it long term, daily basis for about a year in the past, and I never noticed anything like that.

I found that Gabapentin consistently raised my mood.

Pregabalin is pretty much the same as Gabapentin, I can't tell much of a difference besides in the onset, actually. It might be worth a try though.

We really don't know much about how it works, though.

Gabapentin may inhibit synaptic transmission in the mouse spinal cord dorsal horn through a preferential block of P/Q-type Ca2+ channels

Katharina Bayer , Seifollah Ahmadi and Hanns Ulrich Zeilhofer Corresponding Author Contact Information, E-mail The Corresponding Author
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054, Erlangen, Germany
Received 6 August 2003; Revised 29 October 2003; accepted 12 November 2003. Available online 23 January 2004.

Abstract

Gabapentin is a lipophilic analog of γ-amino butyric acid (GABA) with therapeutic activity against certain forms of epilepsy and neuropathic pain. Despite its structural similarity to GABA, it does not bind GABAA or GABAB receptors and the mechanism, especially of its analgesic action, has remained elusive. Here, we have studied its effects on synaptic transmission mediated by the major spinal fast excitatory and inhibitory neurotransmitters, Image-glutamate and glycine, in the superficial layers of the spinal cord dorsal horn, a CNS area, which is critically involved in nociception. Gabapentin reversibly reduced evoked excitatory postsynaptic currents mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA-EPSCs) and inhibitory postsynaptic currents mediated by glycine (gly-IPSCs). Inhibition of AMPA-EPSCs and gly-IPSCs occurred with similar potencies (not, vert, similar10–50 nM) and by about the same degree (not, vert, similar40% at 1 μM). Gabapentin did not affect membrane currents elicited by exogenously applied glutamate or glycine arguing against a postsynaptic site of action. Selective blockade of N-type Ca2+ channels with ω-conotoxin GVIA dramatically increased and blockade of P/Q-type channels with ω-agatoxin IVA strongly attenuated inhibition of evoked synaptic transmission by gabapentin. These results show that gabapentin affects both excitatory and inhibitory spinal neurotransmission via a presynaptic mechanism which preferentially involves P/Q-type Ca2+ channels.

 

[melange]

yes when I take a dose of 2-3 grams the stuff really cranks me up

like hardcore



I am ready to do anything

 

[melange]

I love the stuff though, and would love to see more info on how it works

 

[Ham-milton]

I love it too, but it doesn't lend itself to long term use. Tolerance rises so quickly- and once you're beyond 4 grams at a dose, you're not gonna get much out of 9, either.

It comes down fairly quick, but it's never the same, IMHO.

still, I love it, and the fact that I get it by the boatload from my doc. It's probably the only substance I'll be able to get for life. Until pregabalin goes generic, I'll live with that.

 

[Adrenochrome]

I love it too, but it doesn't lend itself to long term use. Tolerance rises so quickly- and once you're beyond 4 grams at a dose, you're not gonna get much out of 9, either.

It comes down fairly quick, but it's never the same, IMHO.

still, I love it, and the fact that I get it by the boatload from my doc. It's probably the only substance I'll be able to get for life. Until pregabalin goes generic, I'll live with that.

does it synergies w/ d-amph?

(therapeutically or otherwise)

 

[Ham-milton]

I'm sure I've combined them (well, d,l amphetamine), but I can't really say. To compare them, though, I'd say gabapentin is more similar to cocaine and alcohol. Speed doesn't make me chatty, or manic- at least at the doses I've used- but neurontin does that really freakin well. It also leaves HR untouched.

It's been a while since I've had amphetamine, but honestly, gabapentin is more enjoyable.

 

[Riemann Zeta]

^^^^Weird. That is quite a unique response to gabapentin. Consider yourself lucky, I suppose.

I've never tried it, but have always wondered about it (well, more about pregabalin). I take lamotrigine for my bipolar tendencies and it seems to work pretty well, so I wonder how I would react to gabapentin. I know a person who tried it for neuropathic pain and she hated it--the mind-numbing and sedative-type effects were too intense for her to tolerate. Are you feeling foggy in the head, or are you truly depressed in an anhedonic sense? Either way, gabapentin has some really wiggy cognitive effects for certain people.

Gabapentin and pregabalin appear to have the same mechanism of action (binding as antagonists of the a2d N-type Ca++ channel auxillary subunit...I think), but pregabalin is better absorbed and more potent. I do really wonder why pregabalin had to be scheduled in the US; I don't think it is scheduled in any other country in the world...it does sound like a worthwhile anxiolytic, though. And it seems like a better option than a benzo, lacking those pesky sedative and amnesiac effects.

 

[paranoid android]

Well id like to get lyrica but it's really expensive and my insurance does not cover it. It covers gabapentin but only under special authorization and that took a few months to get approved. Theres no way i can afford lyrica right now.

Well gabapentin seems to not mess up my head unless i get majorly depressed and it makes me have a real lack of energy. Then my memory might get shotty like it always does when im majorly depressed. Occasionally i will get kind of cranked up where i suffer from a mixed state which is absolutely awful.

Ive been on benzos (clonazepam) for 2 years and at 6mg's a day for over a year and it never has any effect on me like this even though benzos sometimes dull peoples emotions. They actually made me feel more energetic by lifting my anxiety, stabilizing my moods a little bit atleast and it had a weird effect of actually improving my memory. If i take a extra pill when im manic or mixed then it helps without causing a depression.

I was actually on clonazepam long before i was on gabapentin and i used amitriptyline back then for neuropathic pain. Well clonazepam is used as a treatment too for the type of neuropathic pain i have so thats another thing that helps abit. But as soon as i got the diagnoses of bipolar i was yanked right off the amitriptyline. It had stopped working by then anyway for some stupid reason it just kind of crapped out.

The first drug i tried carbamazepine made me sicker then ive been in my life so that was taken off the table as a option pretty quick. I wouldnt be able to take it now because of it's enzyme inducing properties so i would need more lamotrigine and i have no idea what it would do to the clonazepam which i also need.

So all in all there are not a whole lot of options that i can afford. The fentanyl patch seems to be working better then any other opiate or any other med ive tried so all in all thats pretty good. My depression has lifted over the past few days as well so i don't know what to think of it all. It might have been the pain that never stayed away for more then a few days making everything worse as well. My mood swings just seem to come and go although pain does aggravate it alot and im sure the winter weather ain't helping.

Lamotrigine is also used to treat trigeminal neuralgia (off label like everything else except carbamazepine) which is what i actually have and maybe when i get the dose upped to the 200mg's a day mark that might help and i won't need any gabapentin.

Thanks alot for the replies guys. Much appreciated.

 

[Riemann Zeta]

Beyond 4g, gabapentin saturates the (l)-amino acid transporter, hence anything more in terms of dosage is probably just going down the crapper (literally). As for a 'recreational' dose: hmm, since only certain people like the drug and it is known to cause a diverse spectrum of reactions, it is hard to say. It has to be in the gram range, though (gabapentin is a weak compound).

 

[Adrenochrome]

Beyond 4g, gabapentin saturates the (l)-amino acid transporter, hence anything more in terms of dosage is probably just going down the crapper (literally). As for a 'recreational' dose: hmm, since only certain people like the drug and it is known to cause a diverse spectrum of reactions, it is hard to say. It has to be in the gram range, though (gabapentin is a weak compound).

Where'd you learn about the (l)-amino acid transporter? I know nothing of amino acid transporters and as a bio student I should learn...

 

[mitragyna]

does it synergies w/ d-amph?

(therapeutically or otherwise)

I'm also really curious about this. Would it sort of take the nervous edge off the amph?

 

[wungchow]

gabapentin is AWESOME with a couple beers.

 

[mitragyna]

Im -scripted- 4200 mg a day. It may be because of tolerance but I usually take 20 g as a recreational dose. I get slight visuals and a pretty nice euphoria/benzo feeling, and sometimes have manageable amount of discordination. What is the "common" range of usual recreational use?

I take gabapentin for anxiety and depression, and It has generally worked very well over a long period of time for me. Havent heard of it making anyones depression worse...

20 grams is a helluva lot of Gabapentin IMO. Remember, the more Gabapentin taken at one time, the lower the bioavailability. This is why my doc tells me to space out the doses and don't double up.

Taking Gabapentin with food also increases bioavailability by 14%.

Pharmacokinetic data

Bioavailability Rapid, in part by saturable carrier-mediated L-amino acid transport system
60% for 0.9 g daily to 27% for 4.8 g daily dose
Food increases absorption by 14%

Protein binding Less than 3%

Metabolism Not appreciably metabolized

Half life 5 to 7 hours

Excretion Renal

These interactions may also be useful to know:

Drug Interactions

Antacids: Antacids may reduce the bioavailability of gabapentin by ~20%; gabapentin should be taken at least 2 hours following antacid administration

Cimetidine: Cimetidine may increase gabapentin serum concentrations; clearance of gabapentin is decreased by 14%

Felbamate: Serum concentrations may be increased by gabapentin; monitor for increased felbamate effect/toxicity

Morphine: Serum concentrations of gabapentin may be increased during concurrent use.

Norethindrone: Gabapentin may increase Cmax of norethindrone by 13%

Phenytoin: Phenytoin serum concentrations may be increased by gabapentin; limited documentation; monitor. Note: Valproic acid, carbamazepine, and phenobarbital do not seem to be affected by gabapentin.

 

[delphinen]

I'm just having an amazing Gabapentin high right now, but is a RULE to wait at least a month in my case to get high with it. Taking it daily like for a week makes my tolerance go to the roof, and after that I begin practically don't feeling it, and have to mix to Pregabalin (Lyrica).

But the monthly Gabapentin high it's really amazing, it feels like a mixture of Codeine and MDMA; it also gives me the munchies badly (eating feels goood) and because the Gabapentin becomes a little speedy after 3G, 2 or 4mg of Alprazolam makes it a wonderful experience.

In resume, I wonder if Gabapentin could make the depression of a person worse, but I would ask my doc to switch to Pregabalin (Lyrica).

 

[negrogesic]

Gabapentin is indeed a rather curious compound. I have been evaluating the odd 'anti-addictive' properties of the compound at high doses (300mg qid or more), and am intrigued and quite honestly, a bit confused about how to evaluate my finds. Excuse the ambiguity; I cannot comfortably get into specifics here. All I can say, is that the off-label usage of high dose neurontin in a inpatient setting is becoming increasingly commonly in more 'progessive' facilities.

What I can personally attest to, having recently toyed with large doses of the compound, is that despite its relatively low potency, it is (subjectively) superior to pregabalin. I also find it to be a strong appetite stimulant. Unfortunately, I have personally found its pharmacokinetic profile to be somewhat disappointing.....

 

[ebola?]

We might want to steer conversation back to the original question and discussion of neuropharmacology. It doesn't seem too puzzling to me that Gabapentin causes depression in some individuals, as the drug overall reduces of glutaminergic transmission downstream (pentin's effects on monoamines are less clear, but possibly inhibitory), also enhancing catabolism of glutamate to GABA. Such reduced neural signalling could exacerbate mood disorders. Even benzodiazapines can exacerbate depression in some individuals, but this is pretty idiosyncratic ('depression' must be neurochemically diverse).

What puzzles me is why gabapentin has a uniquely rapid pattern of tolerance accrual. And then can anyone trace out the downstream effects of Ca channel blockers step by step?

ebola