9 replies to this topic

[berry]

Hi, my knowledgeable friends,

Background here, question below:

I was prescribed some modafinil/provigil to help with the constant fatigue that I experience, which is exacerbated with a depressive episode. It came from a GP who was very familiar with my condition and has experience with the drug, and he had suggested it to me prior to this time as well, so I talked to him about it and started it. This was partly due to the fact that I couldn't get in contact with my pdoc, and partly because i already had the idea of what might help.

Through various forums i've heard of quite a number of people with bipolar or mood disorders of some kind who take provigil, and not just for narcolepsy or shift work sleep disorder. It did not strike me as a terrible thing to do, especially since i have a pretty good history of having good insight into when my mood episodes are starting and it was not being abused to get high, just staying awake during the day, giving me enough energy to do the basics.

So pdoc freaked out and ordered me off it, he's conservative and said he'd never use it on anyone because he thinks its experimental and would cause harm and anything else negative you can think of about it etc.


Question:

Does anyone know how this works? What is it doing in my head? I'm studying pharmacology but its too new for my textbooks. Is it really that similar to amphetamines, and I'm interested in everything there is to know about this drug.

berry

[Serpens]

Provigil is a non-amphetamine drug somewhat humorously known as a 'wakefulness promoting agent' - The exact mechanism of how it does what it does is almost completely unknown. There are a variety of theories, including interacting with H1 histamine systems in the brain, GABAergic neurons, and Glutamate/NMDA/AMPA receptors. None of these has been explicitely validated.

It does increase the activity of virtually every major neurotransmitter system in the brain.

What is clear is that it is not similar to amphetamines at all. There is no similar mechanism of action, or chemical structure between the two drugs. This is part of why Provigil is so popular.

It's also mired in a mess of off-label use near the size of Neurontin. Cephalon, the manufacturer has been sued for promoting off-label uses and lost badly. While it is being used as adjunct treatment to depression and drug-induced fatigue there is frighteningly little good science done on how useful or safe the drug is to do this with. There's a great deal of divided opinion on this use - some stating that it's unjustified, unknown and risky. The other side of the coin is that the alternatives are amphetamines.

[bourne]

Provigil is a non-amphetamine drug somewhat humorously known as a 'wakefulness promoting agent' - The exact mechanism of how it does what it does is almost completely unknown. There are a variety of theories, including interacting with H1 histamine systems in the brain, GABAergic neurons, and Glutamate/NMDA/AMPA receptors. None of these has been explicitely validated.

It does increase the activity of virtually every major neurotransmitter system in the brain.

What is clear is that it is not similar to amphetamines at all. There is no similar mechanism of action, or chemical structure between the two drugs. This is part of why Provigil is so popular.

Serpens nailed it all on the head - it works, no one knows why, and it lacks the negatives of amphetamines. ISTR the military did a study where they kept people usefully alert for 40 hours on it, and then they were able to go to sleep normally (e.g., without the crash of amphetamines).

I take 200mg daily (sleep apnea, plus whatever crap Depakote throws my way) and the only time it has ever generated a noticeable mood reaction is when taken exactly concurrently with coffee. In normal use, it does not seem to destabilize my mood in any way.

[mickmax]

I take it for 3rd shift. but i have been off for 3 weeks due to a car wreck and take it every day anyway and have not noticed any mood changes. I noticed when i first started taking it that i was a little wired, but then i got used to it.

[berry]

Thankyou Serpens, Bourne and mickmax, your replies are greatly appreciated.

I guess there is no way to really find out these kinds of things until the people with money do more research. I wasn't impressed with my doctor comparing the drug to amphetamines because besides the fact that its a stimulant, its different for the reasons you've already said.

It makes sense to be cautious of drugs that have little evidence and research behind them. But realistically, psychiatrists have been treating people for years with drugs they didn't understand and that have significant risks. I'm not sure in this case, whether i am unreasonably enthusiastic about wanting to continue my trial of the drug, or whether my pdoc is just really very conservative. I can see his point though. It would be risky to have a patient on a drug that you don't really know anything about.

I've got a referral to another pdoc, to get a second opinion about it. I guess if the consensus is no, then i'll deal with it.

I tried it for about a month and I was more alert, it didn't stop me sleeping, for example I could take it, concentrate on work and then take a 2 hour nap in the middle of the day. I slept a couple hours less at night, but that brought me back to my 'normal' amount of sleep rather than oversleeping. And I felt generally very good. As a result, ate better, exercised more, did stuff in general. In my opinion (obviously i'm not a doctor though) that seems to be a positive reaction to it and nothing horrible happened.

Have to wait and see I guess. I'll be eagerly awaiting the research that will eventually come!

Thanks once again for your replies.

berry.

[bourne]

I've got a referral to another pdoc, to get a second opinion about it. I guess if the consensus is no, then i'll deal with it.

I tried it for about a month and I was more alert, it didn't stop me sleeping, for example I could take it, concentrate on work and then take a 2 hour nap in the middle of the day. I slept a couple hours less at night, but that brought me back to my 'normal' amount of sleep rather than oversleeping. And I felt generally very good. As a result, ate better, exercised more, did stuff in general. In my opinion (obviously i'm not a doctor though) that seems to be a positive reaction to it and nothing horrible happened.

It looks to me like you've got your second opinion right there.

If that was your experience, then the lack of positive or negative information about the drug in general shouldn't be a hindrance. As you point out, "psychiatrists have been treating people for years with drugs they didn't understand and that have significant risks." Most of those drugs also have known really really nasty side effects, unlike Provigil.

Is there any possibility that insurance is an issue? Provigil is one of the newer drugs that they wish the doctors wouldn't prescribe until there's a cheaper generic. (Correct me if I'm confused and generic is already available).

[Anna]

I love provigil for my ADHD sx.

Was on adderall for awhile when I was trying to limit my copays, and it was a very "dirty" drug to me.... Lots of side effects. Provigil seem sto have have almost none, for me at least.

Once a drug is approved for one condition, it has been trialed as "safe enough".


Now, granted, narcolepsy is a nasty condition and one might accept some pretty harsh side effects as a reasonable trade off, but it doesn't seem to do anything tragic that I know of like chew through your liver, or destroy any major organ systems or anything. It's got no black box warnings that I know of.

Anna

[jook]

Provigil is a damned good med for depression for patients who can't take ADs or Lamictal (like me).
I can tell when I miss a dose because I will feel out of sorts and a bit lower.

jook

[Serpens]

Hm. Micromedex has a category IIb Evidence grade B rating for Provigil for Adverse Drug Reactions of Hypersomnolence.

Some get me a prior authorization. I'm going to run me a test case.

Nuvigil, Provigil's semi-evergreened-might-be-better-oh-wait-its-a-god-damned-R-enantionmer-only has... issues relating to the evidence supporting it - as in it's piss poor.

[berry]

I've got a referral to another pdoc, to get a second opinion about it. I guess if the consensus is no, then i'll deal with it.

I tried it for about a month and I was more alert, it didn't stop me sleeping, for example I could take it, concentrate on work and then take a 2 hour nap in the middle of the day. I slept a couple hours less at night, but that brought me back to my 'normal' amount of sleep rather than oversleeping. And I felt generally very good. As a result, ate better, exercised more, did stuff in general. In my opinion (obviously i'm not a doctor though) that seems to be a positive reaction to it and nothing horrible happened.

It looks to me like you've got your second opinion right there.

If that was your experience, then the lack of positive or negative information about the drug in general shouldn't be a hindrance. As you point out, "psychiatrists have been treating people for years with drugs they didn't understand and that have significant risks." Most of those drugs also have known really really nasty side effects, unlike Provigil.

Is there any possibility that insurance is an issue? Provigil is one of the newer drugs that they wish the doctors wouldn't prescribe until there's a cheaper generic. (Correct me if I'm confused and generic is already available).

Yes well I tried to point that out but that didn't seem to help my case. Its become a no-go issue with current pdoc, hence the referral to no. 2

Insurance is not the issue, because i'm in Australia. generally our medication is mostly covered by the PBS (pharmaceutical benefit scheme - i.e. pay $30 and the gov pays the rest). Except in this case its only approved for Narcolepsy here (unfortunately not even shift work sleep disorder). And its really strictly regulated so I pay full price for it, which is $235. Expensive but worth it if it helps.

Interesting that you take it for ADHD Anna, the provigil makes me feel quite focused but in a calm way, not like rockets firing which is how I would imagine myself on amphetamines. Or worse. Which would then make me wonder whether i really have BP or if its ADHD but these days i dont really care any more, the meds mostly work, good.

Hypersomnolence - well, i think now we've got both ends of that spectrum covered!

There seems to be a fair few anecdotal accounts of using provigil for depression and it working well. Unfortunately doctors don't read forums. At least not mine anyway.