Valcyte is a very complex drug. As a result, this post is a bit complex, but please bear with me, as I think I can answer your questions.
Valcyte has several known therapeutic modes of action, as well as many, many possible negative side effects of varying severity. Ganciclovir (the active metabolite of Valcyte) was originally developed as an antiviral for AIDS patients who had CMV retinitis. Ganciclovir was actually extremely effective against all herpes viruses, but due to its great toxicity, especially in the AIDS population, it was reserved for those patients who had CMV retinitis, and who therefore risked losing their sight.
Ganciclovir and Valcyte are much less toxic in the ME/CFS population than in the AIDS population, but they still have the same potential side effects, which is why regular blood monitoring is required. However, due to the lesser toxicity, Valcyte is sometimes used to treat herpes viruses other than CMV (such as EBV) that have proven resistant to other antivirals.
So Valcyte's antiviral effects were the first therapeutic mode of action of the drug to be discovered, and remain its only FDA approved usage.
About a decade ago, Dr. Jose Montoya discovered two other therapeutic modes of action of Valcyte. First, Valcyte, can work as an immunomodulator, making the immune systems of some people work better. Second, Valcyte can act as an inhibitor of microglial inflammation, which is widely believed to cause a number of symptoms of ME/CFS.
Insomnia is one of the more common side effects of Valcyte. This insomnia is often accompanied by extra energy during the day; depending on the person, this extra energy may appear in a pleasant or unpleasant way. For example, when this extra energy manifests as too much energy, it may be experienced as agitation, which is another side effect listed in the prescribing information for Valcyte. However, in some people, the extra energy appears in a calmer way, and is experienced as being very beneficial.
After about 2 weeks it seemed to really kick in and give me tons of energy... I felt wonderful. Overall I thought I was 95% better and felt like I finally found the treatment that would keep me healthy long term.
I could have written the above quote myself about my early treatment on IV ganciclovir (this was before the release of Valcyte). The extra energy kicked in right at the two week mark, which is very common. But this is way too early for any of the known therapeutic effects to be having such a profound impact. So what's happening?
A couple of years ago I discovered that Valcyte has the interesting property that for certain side effects, it can serve as its own antidote. I observed this both in me and a number of other people. For example, over the years I became sensitized to many medications, including Valcyte. With Valcyte, taking even an eighth of a tablet would result peripheral neuropathy that would take many weeks to disappear. I sadly concluded that my days of taking Valcyte were over.
Around then, I was following the posts of another PR member who was also very sensitive to drugs, and for this reason, she had started Valcyte at an eighth of a tablet also. After one dose, she experienced bad vertigo (another known side effect), which slowly declined but wouldn't go away. She knew the benefits of Valcyte, though, and wanted very much to try it. I suggested that she check with her doctor, and if it was OK with him, try 1/32nd of a tablet once the vertigo disappeared completely.
Almost a week later, the vertigo had declined, but was still hanging on. She took the smaller dose of Valcyte anyway, and the vertigo was gone within hours.
I was fascinated. What mechanism could possibly explain that result? And would it work for other side effects? I decided to take one eighth of a tablet of Valcyte again. Sure enough, it gave me peripheral neuropathy. So the next day I took 1/32nd of a tablet, and the peripheral neuropathy disappeared within hours.
Over time, I found that this property held for a number of other neurological side effects as well, such as tinnitus, and this reversal of side effects was experienced by a number of people.
Eventually I came up with a model that explained what I thought was happening here. One of the things that happens with microglial inflammation is that the amount of glutamate increases. Glutamate is an excitatory neurotransmitter, and depending on where it's produced, it may either cause or at least play a role in all of the side effects I have mentioned. So it certainly seemed possible that the lower doses of Valcyte were getting rid of the side effects I mentioned by inhibiting microglial inflammation, and thereby inhibiting the production of excess glutamate.
But what was causing the side effects in the first place? Since glutamate can play a role in all of these side effects, it seemed reasonable that there was something in Valcyte that was acting as a glutamate agonist, either mimicking or increasing the effects of glutamate, directly or indirectly.
This means that Valcyte would have two independent effects involving glutamate - one that would increase it, and one that would decrease it. Depending on the biology of the person involved and the dose of Valcyte, one or the other of these effects would predominate. In general, the higher the dose, the more likely that the glutamate agonist effects would predominate, and the greater the likelihood that negative neurological side effects would appear.
As glutamate is an excitatory neurotransmitter, it can easily be responsible for insomnia. In some people, it can be responsible for increased energy as well. These are typically people who respond positively to stimulants, or drugs such as Provigil (which technically is not a stimulant).
If a dose of Valcyte can be found that produces extra energy with little or no insomnia, then this is ideal. (I experienced some insomnia along with my increased extra energy, but the insomnia gradually disappeared on its own.) However, it's really not a good idea to take drugs long term to suppress the insomnia. The reason for this is that such drugs do nothing to suppress the excess production of glutamate, and excess glutamate is neurotoxic in large enough amounts, or over long enough periods of time. This can cause long term and possibly permanent problems that result from nerve cell death due to glutamate neurotoxicity. It's the same reason that excessive amounts of stimulants over long periods of time can cause problems.
So basically, you've been benefiting from using Valcyte for its stimulant properties. This is not intrinsically a bad thing; there is a subset of people with ME/CFS who benefit from the proper use of stimulants (or Provigil), and these drugs can be of major help for them in their illness. With Valcyte, the stimulant effect can also work synergistically with the other therapeutic effects. Specifically, more and more evidence has been accumulating about the connection between the brain and the immune system. If the brain is working better, which is what the stimulant effect is doing, then the immune system can work better, and then Valcyte can have a major, lasting positive impact on this illness. The key is to moderate the dose of Valcyte so that the stimulant effects don't get out of hand (e.g., don't create intractable insomnia). In your case, if 1800 mg is too high (which it is long term for most people) and 900 mg is too low, why not ask your doctor about trying 1350 mg? Typically, that would be done as 900 mg for the first dose and 450 mg for the second. Since your doctor approved both the 1800 mg and 900 mg doses, I would think that he or she would be quite open to a 1350 mg dose.
A dose in the middle like this might not give you quite the energy as the 1800 mg dose, but it is definitely better to err on the side of caution here. Furthermore, I found in my own experience of taking Valcyte for many years that even when taken at a dose where the energy boost is not as great initially, over time it tends to grow, and does so without any increasing side effects.
