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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by AndrewB on July 23, 2000, at 20:09:43
Some people have a paradoxical response to Provigil, getting either tired or depressed. Dr. Goldstein (a CFIDS specialist), at his website, notes that some people will have a poor response to modafinil. Modafinil is the active ingredient of Provigil. Dr. Goldstein explains that the adverse reaction is due to an increase in the neurotransmitter glutamate. Some people don’t respond well to increased glutamate. Provigil increases glutamate levels. Its normally arousing effects may be due to ability to increase the glutamate to GABA ratio in the hippocampus. Glutamate is the most dominant neurotransmitter in the brain. One of glutamate’s targets is the NMDA receptor.
Of course, if Provigil doesn’t work one can try other arousal agents that work via various mechanisms; adrafinil (what mechanism?), reboxetine, selegiline, wellbutrin and so on.
I get the impression from information on Goldstein’s website that a poor reaction to Provigil may mean a good reaction to Riluzole and Lamotrigine. Both reduce glutamate. Riluzole is expensive and requires bimonthly testing though. I find it interesting that Dr. Goldstein has used lamotrigine with success for CFIDS patients.Note to Scott: Your positive response to lamotrigine yet poor response to Provigil seems consistent with this information. Goldstein identifies neurontin as an (indirect) NMDA antagonist. Goldstein’s methods apparently indicate the use of cycloserine, a partial NMDA agonist, when an NMDA antagonist has an adverse effect. Cycloserine’s normal use is as broad spectrum antibiotic to treat tuberculosis. Animal studies indicate that it has an antidepressant effect within a certain dosage range. Human studies indicate that it confers significant cognitive enhancement upon Alzhiemer’s patients. I don’t know what its effect on bipolar patients may be, it can act as a proconvulsant with some people and perhaps an anticonvulsant in others.
I hope this post motivates you to read up on glutamate and its effects. The involvement of glutamate, glycine and their receptors in depressive disorders is not just a subject of recent academic interest. Drugs that act on these systems (i.e. lamotrigine) are available for the treatment of those with a dysregulation in these parts.
AndrewB
Posted by SLS on July 25, 2000, at 7:49:45
In reply to Why Provigil makes a person feel worse: Scott, posted by AndrewB on July 23, 2000, at 20:09:43
Dear Andrew,
Thanks much for the information and your concern to have looked into this.
Yes. Provigil made me much worse. What's more, I have felt even worse since discontinuing it. I only took it for five days. It left me really screwed-up for over a week. I am only now beginning to return to my usually crappy existence. I had thought perhaps that the worsening of depression and the other cognitive disturbances I experienced were the result of Lamictal and Provigil exerting opposing effects on glutamate. I hadn't thought that the effects of Provigil in and of themselves may have been harmful. I guess they are.
I am afraid to go near adrafinil at this point. Unless I am sure that it does not share the glutamatergic properties of Provigil, I can't afford to. I certainly don't have it within me to endure any more such negative reactions to drugs as I have had since March. Reboxetine made me much worse. I experienced a negative reaction to Neurontin, the effects lasting for at least a month after discontinuing it. Including Provigil, I have had to experience dysphoria, cognitive disturbances, catastrophic thinking, and suicidality for weeks at a time. I don't know how much I will be participating on Psycho-Babble. Actually, I am surprised that I pushed myself to go on-line this morning. I was rewarded for doing so by finding your post. It couldn't have come at a better time. I am very shaken by what has happened to me.
I have watched you learn and grow over the last few months. Your knowledge and understanding have become quite impressive. I am grateful for your research and input regarding my condition.
What is the URL for Dr. Goldstein's website?
Thank you very much.
Sincerely,
Scott
Posted by Ant-Rock on July 25, 2000, at 12:17:40
In reply to Re: Why Provigil makes a person feel worse: Scott » AndrewB, posted by SLS on July 25, 2000, at 7:49:45
Scott,
I'm very sorry to hear of your latest struggles. All I can say is that I can certainly relate to having a severe adverse reaction that causes an extreme worsening of depression. I know things suck right now, but please give yourself enough time to deal with it. Don't put pressure on yourself to speed up your recovery. I had to keep telling myself this is not my fault and however long it takes to get back on my feet, one month or one year, so be it.
This is my advice, for what its worth.
Please take care,
Sincerely,
Anthony
Posted by SLS on July 27, 2000, at 10:05:43
In reply to Re: Why Provigil makes a person feel worse: Scott » SLS, posted by Ant-Rock on July 25, 2000, at 12:17:40
Thanks, Anthony.
This really helped.
- Scott
> Scott,
> I'm very sorry to hear of your latest struggles. All I can say is that I can certainly relate to having a severe adverse reaction that causes an extreme worsening of depression. I know things suck right now, but please give yourself enough time to deal with it. Don't put pressure on yourself to speed up your recovery. I had to keep telling myself this is not my fault and however long it takes to get back on my feet, one month or one year, so be it.
> This is my advice, for what its worth.
> Please take care,
> Sincerely,
> Anthony
Posted by BillP on July 29, 2000, at 12:00:32
In reply to Re: Why Provigil makes a person feel worse: Scott » AndrewB, posted by SLS on July 25, 2000, at 7:49:45
I was interested to read this comment:
>
> Yes. Provigil made me much worse. What's more, I have felt even worse since discontinuing it. I only took it for five days. It left me really screwed-up for over a week.
- - - - - - - - - - -
I took Provigil for eight days, and it took me about eight or nine more days after that to fully recover from it. I am so glad to find out that I am not the only one who reacts this way.By the way, what is the URL for Dr. Goldstein's website? I would like to know, too.
Posted by SLS on July 29, 2000, at 13:04:56
In reply to Re: Why Provigil makes a person feel worse, posted by BillP on July 29, 2000, at 12:00:32
Hi Bill.
It did indeed take me nine days to recover from the Provigil-induced worsening of depression and other associated cognitive disturbances. Because I discontinued two drugs on the same day, I did not know for which to attribute the post-discontinuation worsening to. Having been treatment-resistant for so long, I was afraid to leave Provigil without being sure that it was the culprit. After I had begun to feel recovered from my first trial of Provigil nine days after having discontinued it, I decided to restart it to be sure. Although I cringed at the thought of going through that hell again, I cringed more at the thought of passing over a drug that I might respond to. I took one 50mg dose of Provigil last Sunday morning. By Monday morning, I was pretty much screwed up again. On both occasions, the fifth day following discontinuation was the worst.
Thanks for posting your experience. It is somehow reassuring to know that I am not the only one who has reacted this way. I wish you luck on your future treatment trials.
- Scott
> I was interested to read this comment:
> >
> > Yes. Provigil made me much worse. What's more, I have felt even worse since discontinuing it. I only took it for five days. It left me really screwed-up for over a week.
> - - - - - - - - - - -
> I took Provigil for eight days, and it took me about eight or nine more days after that to fully recover from it. I am so glad to find out that I am not the only one who reacts this way.
>
> By the way, what is the URL for Dr. Goldstein's website? I would like to know, too.
This is the end of the thread.
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