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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by IsoM on April 2, 2002, at 2:10:01
Thanks for taking the time to read & answer all the posts, Dr. Kramer.
Many people have experienced discontinuation/withdrawal problems when stopping SSRIs, even over a long period of time. A number have even had long-lasting problems. I was one of them.
When I stopped Luvox (over a 3 month period of gradually diminishing doses), I still never felt 'normal' until I went on Paxil a number of months later. When I weaned off Paxil after 3 1/2 years on it, I had the same reaction. It, too, was done over 3 months when I switched to Celexa. In fact, the vertigo & 'brain zaps' never did leave & necessitated going on 10 mg Paxil daily along with my regular Celexa. It quelled the symptoms but never stopped it completely at that dose.
I have started taking Olmifon (adrafinil) along with the Celexa. I've found that I've been able to completely stop the Paxil & have had no more symptoms. Adrafinil's main metabolite is modafinil (Provigil) so my question is about Provigil & Olmifon.
[Question #1]
Can you hazard a guess as to why modafinil was able to stop these discontinuation symptoms? A report entitled "Adrafinil: A Novel Vigilance Promoting Agent"
from CNS Drug Reviews Vol. 5, No. 3, pp. 193-212 © 1999 Neva Press, Branford, Connecticut
suggested that adrafinil (modafinil) had the effect of boosting overall brain metabolism and that it affected various neurotransmitters.[Question #2]
Have you ever heard of Provigil being used to treat discontinuation problems in patients stopping an SSRI?[Question #3]
Would you hazard a guess that it may be a potential medication used in that manner? Any thoughts on this?I seriously wonder if Provigil might not be a good strategy for doctors to use on patients with severe symptoms.
Posted by Dr. Kramer on April 2, 2002, at 12:14:52
In reply to Kramer re: SSRIs/Discontinuation symptoms/Provigil, posted by IsoM on April 2, 2002, at 2:10:01
> Thanks for taking the time to read & answer all the posts, Dr. Kramer.
>
> Many people have experienced discontinuation/withdrawal problems when stopping SSRIs, even over a long period of time. A number have even had long-lasting problems. I was one of them.
>
> When I stopped Luvox (over a 3 month period of gradually diminishing doses), I still never felt 'normal' until I went on Paxil a number of months later. When I weaned off Paxil after 3 1/2 years on it, I had the same reaction. It, too, was done over 3 months when I switched to Celexa. In fact, the vertigo & 'brain zaps' never did leave & necessitated going on 10 mg Paxil daily along with my regular Celexa. It quelled the symptoms but never stopped it completely at that dose.
>
> I have started taking Olmifon (adrafinil) along with the Celexa. I've found that I've been able to completely stop the Paxil & have had no more symptoms. Adrafinil's main metabolite is modafinil (Provigil) so my question is about Provigil & Olmifon.
>
> [Question #1]
> Can you hazard a guess as to why modafinil was able to stop these discontinuation symptoms? A report entitled "Adrafinil: A Novel Vigilance Promoting Agent"
> from CNS Drug Reviews Vol. 5, No. 3, pp. 193-212 © 1999 Neva Press, Branford, Connecticut
> suggested that adrafinil (modafinil) had the effect of boosting overall brain metabolism and that it affected various neurotransmitters.
>
> [Question #2]
> Have you ever heard of Provigil being used to treat discontinuation problems in patients stopping an SSRI?
>
> [Question #3]
> Would you hazard a guess that it may be a potential medication used in that manner? Any thoughts on this?
>
> I seriously wonder if Provigil might not be a good strategy for doctors to use on patients with severe symptoms.Wow! How wonderful for you that you got that degree of relief, and what a wonderful psychopharm pearl! I've never heard of these drugs being used for SSRI withdrawal.
I'm not familiar with Olmifon, but I know something about Provigil. The problem is that no one knows exactly how it works. It does not seem to be interested in any monoamine receptors (Dopamine, serotonin, or norepinephrine) except glutamate, maybe. Without more data about a mechanism of action, who knows?
Posted by IsoM on April 2, 2002, at 12:33:10
In reply to Re: Kramer re: SSRIs/Discontinuation symptoms/Provigil, posted by Dr. Kramer on April 2, 2002, at 12:14:52
Do you know if Cephalon, the parent company of Provigil, is doing any follow-up studies on it trying to determine Provigil's mode of action in the human brain?
Posted by JohnX2 on April 2, 2002, at 14:13:32
In reply to Kramer- Question on Mode of Action - Provigil » Dr. Kramer, posted by IsoM on April 2, 2002, at 12:33:10
> Do you know if Cephalon, the parent company of Provigil, is doing any follow-up studies on it trying to determine Provigil's mode of action in the human brain?
Hi IsoM,
If Cephalon has the tools and technology to understand their medicine, do you think they would feel a compelling reason to release all their studies?
I do this sort of work at my company analyzing microchips, and we do not generally give out this sort of trade secret information to the general public (at least not anything beyond what is required for marketing). Its not good for competitive reasons.
Regards
John
Posted by IsoM on April 2, 2002, at 16:59:10
In reply to Re: Kramer- Question on Mode of Action - Provigil » IsoM, posted by JohnX2 on April 2, 2002, at 14:13:32
But it's a copletely different business, John. There's stuff my son programs that pretty secretive too, as who wants the competition writing code for the same idea or in the same way?
But microchips & programs don't affect people's health. If you get sick while using a program, no one's going to want to know what its code is. But if a person with an genetic illness suddenly takes a turn for the worse just after they've been prescribed something new, how the med works is a pretty good thing to know.
Provigil is patented for a while so there's no worry someone will make the same thing. But there's definitely going to be interest in making similar medication. If Provigil doesn't bind to any particular neurotransmitter, it's kind of hard to hypothesise on how it works, but they'll still want to know.
If you ever get looking through the thick manuals on medications like the CPS we have in Canada (don't know if it's in the States too), you'll find an explanation for the medications mechanism of action. Generally, there's something on pharmakintetics & pharmadynamics for most medications except the old ones that have been around for a long time. It's no trade secret how meds work & is found in many texts.
One way that I know of on how meds are made is:
the key part of the molecule that fits into a receptor site (it mimics the original natural brain chemical) is tailor made to fit the receptor. Then it gets tested to see if it works in vitro & goes on from there. All the competition has to do is to make another molecule that will fit like the medication that works. Much, much more difficult than it sounds though & can take many years.
Posted by JohnX2 on April 2, 2002, at 20:48:29
In reply to Re: Kramer- Question on Mode of Action - Provigil » JohnX2, posted by IsoM on April 2, 2002, at 16:59:10
These are my thoughts...
I have to be cynical having had dealt with lawyers...I've been surprised at how much information they've requested we suppress... ;-)
> But it's a copletely different business, John. There's stuff my son programs that pretty secretive too, as who wants the competition writing code for the same idea or in the same way?
>
> But microchips & programs don't affect people's health. If you get sick while using a program, no one's going to want to know what its code is. But if a person with an genetic illness suddenly takes a turn for the worse just after they've been prescribed something new, how the med works is a pretty good thing to know.
>Agreed, but..
Cynical...Not if you are the pharmaceutical company. Best little be known about how your product works to avoid liability issues.
If the product could cause a health concern, then it would be best if the public knew less about the product than more.> Provigil is patented for a while so there's no worry someone will make the same thing. But there's definitely going to be interest in making similar medication. If Provigil doesn't bind to any particular neurotransmitter, it's kind of hard to hypothesise on how it works, but they'll still want to know.
>If Cephalon published a report indicating how provigil worked (of course they can't get around the patent disclosures), this may tip off a competitor on a lead to make a pharmaceutical to achieve the same means. It doesn't matter how difficult a copy cat would be, this is what Cephalon's intellectual property attorneys would believe and will try to protect this information regardless of how ludicrous it is for the competitors to impede on their market (this is what the attorneys get paid for).
> If you ever get looking through the thick manuals on medications like the CPS we have in Canada (don't know if it's in the States too), you'll find an explanation for the medications mechanism of action. Generally, there's something on pharmakintetics & pharmadynamics for most medications except the old ones that have been around for a long time. It's no trade secret how meds work & is found in many texts.
>A lot of this information is required for the FDA, etc correct? Exactly what occurs in the brain does not need to be disclosed?
> One way that I know of on how meds are made is:
> the key part of the molecule that fits into a receptor site (it mimics the original natural brain chemical) is tailor made to fit the receptor. Then it gets tested to see if it works in vitro & goes on from there. All the competition has to do is to make another molecule that will fit like the medication that works. Much, much more difficult than it sounds though & can take many years.
Most companies spy on each other by looking at the other companies patent filings.John
Posted by SLS on April 3, 2002, at 10:54:29
In reply to Kramer- Question on Mode of Action - Provigil » Dr. Kramer, posted by IsoM on April 2, 2002, at 12:33:10
> Do you know if Cephalon, the parent company of Provigil, is doing any follow-up studies on it trying to determine Provigil's mode of action in the human brain?
Hi.
I haven't been keeping up with it, but the last time I checked, the only property that researchers seemed to be convinced of is that Provigil (modafinil) promoted an increase in extracellular glutamate. Glutamate is by far the most widespread excitatory neurotransmitter in the brain, and it is thought that Provigil increases glutamatergic activity in several key areas responsible for both wakefulness and vigilance/mood. It is my impression that increased wakefullness is promoted by Provigil in the hypothalamus, and increased vigilance and mood elevation in the hippocampus.
According to what I had read, Provigil does not act as a ligand to stimulate directly any NE receptor. It is not a NE alpha-1 agonist.
- Scott
Posted by JohnX2 on April 3, 2002, at 14:42:27
In reply to Re: Kramer- Question on Mode of Action - Provigil » IsoM, posted by SLS on April 3, 2002, at 10:54:29
> > Do you know if Cephalon, the parent company of Provigil, is doing any follow-up studies on it trying to determine Provigil's mode of action in the human brain?
>
> Hi.
>
> I haven't been keeping up with it, but the last time I checked, the only property that researchers seemed to be convinced of is that Provigil (modafinil) promoted an increase in extracellular glutamate. Glutamate is by far the most widespread excitatory neurotransmitter in the brain, and it is thought that Provigil increases glutamatergic activity in several key areas responsible for both wakefulness and vigilance/mood. It is my impression that increased wakefullness is promoted by Provigil in the hypothalamus, and increased vigilance and mood elevation in the hippocampus.
>
> According to what I had read, Provigil does not act as a ligand to stimulate directly any NE receptor. It is not a NE alpha-1 agonist.
>
>
> - ScottFellas,
I posted a bunch of links on modafinil studies starting here (just a short while ago in fact):
http://www.dr-bob.org/babble/20020322/msgs/100358.html
The studies implied mechanisms showing direct/indirect increases in serotonin conductance, reductions in Gaba, and increases in glutamate conductance.
Its possible to increase serotonin conductance by agonizing somatodendric alpha-1 noradrenaline receptors on serotonergic neorons, but I ?believe? that antagonist medicines at alpha-1 noradrenaline receptors do not block provigil's action (hence the thought that it does not bind to the sight?).
Regards,
John
Posted by disney4 on January 26, 2003, at 12:05:23
In reply to Re: Provigil - serotonin, gaba, glutamate, posted by JohnX2 on April 3, 2002, at 14:42:27
I am on my first day of provigil and am noticing a positive effect. Is it possible that this med could produce enough of an AD effect to be used alone? Also do you think the changes could last when the med is dicontinued, if taken for a year or more, as other strictly AD meds claim? If not, would an add on like Remeron be advisable?
Posted by JohnX2 on January 26, 2003, at 19:03:46
In reply to Re: Provigil - serotonin, gaba, glutamate » JohnX2, posted by disney4 on January 26, 2003, at 12:05:23
This is the end of the thread.
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