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
poster:AndrewB
thread:41275
URL: http://www.dr-bob.org/babble/20000717/msgs/41275.html