Synergistic Effects of Lamotrigine and Vyvanse?

[Lightning-Nl]

I've noticed that it entirely depends on what you're looking for. If you want to be totally jacked the fuck up, don't take Lamotrigine - it will take that feeling away. If you want to get things done, without the compulsive-inducing nature of amphetamine? I recommend you start at 100 milligrams if you've never taken it before.

I remember when my doctor put me on 200 milligrams without tapering me up. I took the Lamictal, and 20 milligrams of Adderall together and got vertigo that was so bad that I had to pull over on the freeway, climb into my backseat, and lay in a fetal position for a couple hours until I could call someone to pick me up and drive me home. That was one shitty day...

 

[AlphaMethylPhenyl]

^it's not good hr advice to tell someone to self medicate with lamictal. people taper up because it helps avoid a life-threatening rash. don't do it unless prescribed.

 

[Lightning-Nl]

^it's not good hr advice to tell someone to self medicate with lamictal. people taper up because it helps avoid a life-threatening rash. don't do it unless prescribed.

While it's true that only a doctor should tell you what medications you should be taking - self-medicating with Lamotrigine is by far one of the most SANE things anyone with mood/depression issues could do. Especially when compared to Heroin, or even something a lot 'tamer' like Ativan or Vicodin.

Personally - I say that if you're going to self-medicate, and you have a choice between Lamictal or illegal drugs... then yes. I will completely ignore HR in that situation and absolutely tell the person to take the lamictal.

 

[AlphaMethylPhenyl]

If bluelight doesn't know that lamictal can cause a fatal rash, now they do. That's why it's by prescription only.

 

[Lightning-Nl]

Why do you keep bumping your own agenda?

That's idiocy. If bluelight doesn't know that lamictal can cause a fatal rash, now they do. That's why it's by prescription only. Don't fuck around with drugs, especially this one.

You may find this post ironic (since you said I'm bumping my own agenda). But you completely disregarded what I was saying. Abusing Lamotrigine is overall much more sane than Vicodin. Yes Lamictal CAN cause a fatal rash. But that's a rare side-effect. RARE. However, the FDA requires that people assume this likely. Which it's not.

 

[theGirlWithBlueHair]

Another possible mechanism mechanism of lamotrigine's stimulant and antidepressant effects also stem from its well documented ability to inhibit GABA release proportionate to dose via it's action on presynaptic sodium channels which prevent the release of all neurotransmitters ( lamotrigine doesn't act on postsynaptic channels). This is why it can cause myoclonus and insomnia as a side effect and seizures and status epilepticus in overdose. Similarly to tiagabine and vigabitrin which indirectly activate GABA B presynaptic autoreceptors inhibiting GABA release.

 

[AlphaMethylPhenyl]

Another possible mechanism mechanism of lamotrigine's stimulant and antidepressant effects also stem from its well documented ability to inhibit GABA release proportionate to dose via it's action on presynaptic sodium channels which prevent the release of all neurotransmitters ( lamotrigine doesn't act on postsynaptic channels). This is why it can cause myoclonus and insomnia as a side effect and seizures and status epilepticus in overdose. Similarly to tiagabine and vigabitrin which indirectly activate GABA B presynaptic autoreceptors inhibiting GABA release.

Ah an old thread. I edited my past post, as it was quite incendiary...an old post, one in a past state of great pain, but one of mine nonetheless.

I thought lamotrigine was an anticonvulsant? Didn't you mention it as such in one of your previus posts? I don't see how this squares with inhibiting GABAergic activity.

I also was under the impression that it's a sigma agonist, about which I don't know much, but I wasn't under the impression that they're entirely presynaptic.

Regarding sodium channels, I'm not quite sure what you're talking about. The positive charge from sodium ion influx carries the threshold of activation from the hillock to the button, creating an action potential. But lamotrigine can't very well infiltrate the presynaptic neuron to somehow alter sodium channels along the axon. That would leave postsynaptic ligand-gated sodium ion channels as a possible (but not at all obvious) site for lamictal to act upon, but again, anticonvulsants don't really create EPSPs. Can you post a source and/or explain this?

It seems that only about 2% of people who take lamictal experience a greater amount of seizures (though this is as an adjunct, and you did say in overdose). Myoclonus is a type of siezure, I thought. 10% experience insomnia. http://www.rxlist.com/lamictal-side-effects-drug-center.htm

I'm genuinely curious, not trying to be confrontational.

 

[theGirlWithBlueHair]

http://scholar.google.com/scholar_u...qxYSDEq-SBd8pitnRoqKEvq-A&nossl=1&oi=scholarr
Sodium channels exist presynaptically as well and that is where lamotrigine binds and controlling transmitter release, they inhibit GABA release as well. I know the study I link to contradicts this but I disagree with them based on other studies and anecdotal and clinical evidence from lamotrigine overdoses, which is when it precipitated convulsions ...not at typical doses.

Actually a lot of anticonvulsants can cause myoclonic jerks and similar such movements like the ones I mentioned along with the gabapentinoids, it's uncommon, buts it's through a presynaptic inhibition of GABA release, which doesn't necessarily underscore their utility as anticonvulsants, as the case with lamictal whose broad spectrum calcium blockade overwhelmingly negates this.

I didn't take anything as confrontational lol.

 

[AlphaMethylPhenyl]

So do you have a source then?

Lamictal would have to infiltrate the presynaptic neuron in order to affect sodium ion channels pesynaptically, which to my knowledge no drug does or can do. I'm sorry but I don't see how that is possible. Are you talking about voltage, or ligand, gated ion channels?

I would think that it would be more of a common side effect if that were the case...I mean it makes sense that blocking calcium anion influx would occur on GABAergic as well as glutamate predominate neurons, but the latter much more so than the former.

I mean, any drug that, in one way or another, overall reduces GABAergic activity, doesn't sound like an anticonvulsant.

Awesome. We're good .

 

[theGirlWithBlueHair]

Were you able to read the pdf from the link I posted? Voltage gated. Yeah it would on glutamatergic which is why lamotrigine has a habit of causing psychotic reactions which I think is mentioned in the study. There are a lot of case report's of people experiencing vivid hallucinations from it, unique from other anticonvulsants.

 

[serotonin2A]

Lamictal would have to infiltrate the presynaptic neuron in order to affect sodium ion channels pesynaptically, which to my knowledge no drug does or can do. I'm sorry but I don't see how that is possible. Are you talking about voltage, or ligand, gated ion channels?

Lamictal inhibits sodium channels on presynaptic axons/terminals. The sodium channels are expressed in the cell membrane and Lamictal can interact directly with the channel without having to cross the cell membrane.

Many local anesthetics block axonal sodium channels -- I'm not sure why you think such an effect is impossible.

 

[Cotcha Yankinov]

Isn't it a possibility that some of the pro-excitability reactions might have to do with inhibiton of GABA neurons and pro-inhibitory pathways? I mean as I understand it that's pretty much how really high dose NMDA antagonists can cause seizures.

Also, my mind is taking a massive dump right now but don't some sodium channel antagonists have higher affinity for the state that occurs after firing, so that the neurons that fire a lot are inhibited more? This could explain its anti manic and anti epileptic properties, while a normal person might be stimulated. In that case, since GABA interneurons have higher basal firing rates (as I recall), couldn't the sodium channel antagonist be preferentially inhibiting the GABA neurons in some cases?

 

[AlphaMethylPhenyl]

Lamictal inhibits sodium channels on presynaptic axons/terminals. The sodium channels are expressed in the cell membrane and Lamictal can interact directly with the channel without having to cross the cell membrane.

Many local anesthetics block axonal sodium channels -- I'm not sure why you think such an effect is impossible.

This is trivializing a bit, but don't sodium channels not exist on the terminal? I thought that was where calcium channels worked.

Hmm, never heard of that. Then again, I don't know the specifics of how any other connections than axo-dendritic ones function. I also don't know much about volume neurotransmission (which by itself opens up the possibility of chemicals working on Na channels) or how cannabinoids facilitate retrograde neurotransmission--this is of course off topic, but I'm assuming they interact with the postsynapic neuron, then somehow relay feedback to the presynaptic neuron, which depending on either exictatory or inhibitory-dominant neurons, act to increase and decrease neurotransmission, respectively.

Cotcha, yes I believe that was part of what girlwithbluehair was saying. I don't doubt your idea of Na antagonism, but I don't quite know how that would work. It would then make sense that it would take one EPSP for any given axon to be inhibited, then? I guess it depends on how often that neuron would otherwise fire. With regards to your final thought, wouldn't that depend on how selective lamictal is for any given neuron? Like, I would think that it would act more so on excitatory neurons. Since glutamate and GABA are not just both amino acids, but are close cousins, I could see how lamictal might inhibit the propagation of the signal from both types.

 

[serotonin2A]

This is trivializing a bit, but don't sodium channels not exist on the terminal? I thought that was where calcium channels worked.

Hmm, never heard of that. Then again, I don't know the specifics of how any other connections than axo-dendritic ones function. I also don't know much about volume neurotransmission (which by itself opens up the possibility of chemicals working on Na channels) or how cannabinoids facilitate retrograde neurotransmission--this is of course off topic, but I'm assuming they interact with the postsynapic neuron, then somehow relay feedback to the presynaptic neuron, which depending on either exictatory or inhibitory-dominant neurons, act to increase and decrease neurotransmission, respectively.

Lamotrigine can bind directly to (and inhibit) certain types of sodium and calcium channels. So lamotrigine floats around in the extracellular fluid in the brain and it inhibits those channels anywhere they happen to be located (dendrite, cell body, axon, terminal).

BTW, both the axon and terminal are considered to be "presynaptic" parts of the cell.

 

[Cotcha Yankinov]

I found a bit about the affinity for different sodium channel states that I was crudely referencing http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857610/ -

"Eslicarbazepine binds avidly and blocks the inactivated voltage-gated sodium channel (VGSC). The VGSC is the major source of sodium entry when a neuron depolarizes, and consequently allows for the action potential to propagate. VGSCs have 3 states. In the deactivated or resting state, the VGSC is closed, but the channel is responsive to a depolarization signal. When the cell depolarizes, the VGSC opens to allow sodium ion entry. After the action potential, the VGSC enters an inactivated state, in which it is closed and not responsive to voltage changes.15 Eslicarbazepine binds to the inactivated form of the VGSC and prevents its reversion to the receptive resting or deactivated form.16,17 This means that eslicarbazepine binds to more active neurons preferentially. This mechanism is shared by carbamazepine, oxcarbazepine, and other anticonvulsants.17,18 The affinity of eslicarbazepine to the inactivated form of the VGSC is similar to that of carbamazepine, but its affinity to the resting form of VGSC is some 3 times less.12,17 This suggests that eslicarbazepine is less likely to bind to normally active neurons, and therefore, less likely to cause adverse neurological consequences. Indeed when compared with either carbamazepine or oxcarbazepine, eslicarbazepine had less neurologic impairment in rats,14 and was less toxic to cultured hippocampal neurons.19"

So I guess the firing rates of neurons is important in determining what activity is suppressed. Interesting to think about because it makes sense that this would be a good class of drugs for bi-polar, in the sense that if you're manic it will antagonize the cells firing really fast, and if you're depressed it might start to exert more of an inhibitory effect on the GABA interneurons or what have you. I don't know what this means for cells that fire rhythmically. It seems like it would disorient that rhythm. Also, I wonder if sodium channels are somewhat equally expressed across all cell types or if there are certain cells that (through the wisdom of nature) have acquired an abundance of sodium channels (As I recall some degree of sodium channel dysfunction/dysregulation or something is involved in some mental illness).

I think retrograde transmission has to do with gaseous molecules like nitric oxide diffusing from post synaptic to pre synaptic (If I recall correctly somehow CB1 facilitates that). Also just thinking about volume transmission hurts my brain lol

Ho-Chi-Minh, mind if I ask if you were ever on sodium channel antagonists, and if yes did they help normalize you?

 

[AlphaMethylPhenyl]

BTW, both the axon and terminal are considered to be "presynaptic" parts of the cell.

Oh, I knew that haha. Didn't mean to say that if I did.

Ho-Chi-Minh, mind if I ask if you were ever on sodium channel antagonists, and if yes did they help normalize you?

I'll look at the other material later.

Why do you ask? I guess this calls for a little MH overlap. I'm not the most stable person, but I'm better than before. Sodium channel antagonists, so inhibitory action. Well I've had some bouts with kava (I think one of the kavalactones is a Na antagonist), also valerian root. I was on lithium, which worked for a while, but it doesn't really deal well with psychotic symptoms. It has yet to be seen if other mood stabilizers improve my condition or not.

I'm definitely not "normal", but I take refuge in the fact that no one really is, and that everyone has things about themselves that they would give a lot to change. I guess my main point would be that it doesn't really matter how a drug works (we're not as close as some would suggest to identifying an action of a chemical with a feeling). What matters is if the person taking it is functional enough for therapy to work. Medication only goes so far, and can take weeks or even several months to help entirely. I guess also one of my ideas is if you're moving forward, things are okay.

 

[Cotcha Yankinov]

I guess I'm curious about what works for other people, studies are great but I like hearing from people first hand, especially if they seem like a similar "phenotype" I guess... Also, sorry if I implied you were mentally unhealthy, if it's any consolation I am batshit crazy most of the time But it is no measure of good health to be well adjusted to a profoundly sick society.

I absolutely agree with cognitive approaches being the long term solution, hopefully one day we will get to the point where we have real biological interventions that make a lasting improvement but I think mindfulness and CBT will still be around thousands of years from now.

I'm curious if you've thought about having your genome mapped with 23andme/promethease. I understand if money is an issue (It's about 200$). I certainly learned some interesting things about myself. Although I suppose if someone has had enough trauma and such the need to search for a genetic component to the mental illness is lessened...

 

[AlphaMethylPhenyl]

No offense taken. I think most intellectual people, including not just us but a great many bluelighters, go through some difficult times.

I haven't really considered that at this point, but I might in the future if my progress stalls. I think I have a good idea of what caused my issues.

Threads like these are just a little silly because if it feels like two drugs synergize to someone, there's really no reason to ask strangers, even if its just placebo or some confounding variable at play.

 

[Cotcha Yankinov]

I find it interesting that you think intellectuals tend to have more issues, I absolutely agree. If you've never seen a film called Proof with Anthony Hopkins I think you might like it (It is about the extreme spectrum of a mix of brilliance and mental illness).

I think especially when it comes to sodium channel antagonists there is no hard and fast rule to how people respond, so other strangers trying the same combo expecting the same effects as the first guinea pig that tried the combo is dangerous IMO....

 

[cr33py]

Ive experienced effects with even smaller doses of lamotrigine, around 25mg along with 20mg amphetamine. Not sure what this combination is doing either, but it doesnt seem to require a full mood stabilizing dose to synergize with amphetamine. Also have experienced (as probably has everyone whos taken it) the startup effects where you feel pretty wired even on small doses. Whats with that??? makes no sense to me.
As you have all said the effects on 5ht3, serotonin and dopamine are rather weak. I have read articles regarding MAOI treatment that suggested effective treatment occupancy levels for MDD so Im assuming there is a way to test for free MAO besides taking a sample from a brain? Might be interesting to see if there are such numbers to see just how much MAO occupancy lamotrigine and the downstream results of its presence are causing.
SJS is pretty rare, but if you were to hit the lottery, it would be by taking a large amount right off the bat. Also, tapering off is recommended like any AED.