The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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Valcyte sleep issues

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by BrianD15, Sep 12, 2017.

  1. BrianD15

    BrianD15

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    Does anyone else have trouble sleeping due to Valcyte? Have you found any way to solve that problem?

    A few months ago I started taking Valcyte 1800 mg (900 mg 2x per day). After about 2 weeks it seemed to really kick in and give me tons of energy. I had trouble sleeping, but found that a tiny dose of melatonin (0.5 mg) solved that problem for me. 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.

    Now fast forward about 2 months. The small melatonin doses are no longer enough to help me fall asleep. Larger doses can get me to sleep but don't keep me asleep. I wake up at 3 am or 4 am and can't get back to sleep for another hour or two. Even though I can get back to sleep, I wake up feeling drained because it's not a deep sleep. During the day I'm back to feeling foggy, working is difficult, and I get frustrated and sad about it.

    When I discussed the problem with my CFS doctor, he told me to drop down to 900 mg (morning only). Within two days I was spending half the day in bed extremely sleepy. I hoped it was just a temporary withdrawal effect so I stuck with this plan. But 10 days later I was still struggling to function. Sleep was way better, but overall I was worse off. The doctor and I agreed that I should step back up to 1800 mg, and I felt improvement the same day. Within the week I felt mentally very clear again. But then the sleep issues set in again and I started to feel worse.

    Maybe it's possible that my worsening is due to Valcyte side effects. But so far I'm keeping my fingers crossed that the loss of benefits / worsening is simply due to the ongoing sleep issues. I'm hoping that if I can solve the sleep problem that I'll feel good again.

    I plan to discuss the need for a sleep aid with my psychiatrist next week. I'm interested to know what has worked for other people on Valcyte.
     
  2. zzz

    zzz Senior Member

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    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.
    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.
     
    RL_sparky and BrianD15 like this.
  3. BrianD15

    BrianD15

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    Thank you for the very thoughtful reply, zzz. This is exactly the kind of intelligent feedback I was looking forward to when I joined the forum.

    I had been suspicious that the benefit I was receiving from valcyte was indeed from a stimulating side effect rather than antiviral activity. The clues for this were:
    • Energy increase started very quickly when I began the drug
    • Insomnia is a clear sign that it has a stimulating effect
    • My CMV IGG titers aren't that high, they continued to drop even before valcyte, and I've actually been IGM negative for a few months. Additionally I was feeling quite well at the time I first contracted CMV (i.e. titers went from negative to positive). All of this suggests that CMV isn't actually playing a big role, or any role, in my recent fatigue
    • Very rapid return of fatigue when lowering dose. (The first two days I was stuck in bed I actually said it felt like the times that I experienced withdrawal as a result of lowering Adderall dose years ago.)
    Additionally I should note that I agree that sleeping pills are not an ideal solution. For at least two reasons:
    • In general I don't like trying to cover up one side effect with another drug, particularly when it's possible to avoid the initial side effect in the first place. (Need to avoid side effects causing a chain reaction of adding more and more drugs.)
    • Sleeping pills lose effectiveness / become habit forming over time.
    So my desire to try sleeping pills ASAP is really because I want to see if the cumulative sleep loss is what's causing me so much difficulty in the daytime (return of brain fog, feeling run down, irritable) at work. In other words, if I feel much better in the daytime after inducing a few nights of great sleep then I can almost "prove" that Valcyte is helpful except for it's sleep effects. On the other hand, if I can induce a few nights of great sleep but I still feel bad in the daytime then it is more likely that my daytime issues are unrelated to sleep. For instance, the daytime issues can be because of the depression and irritability side effects, or I could be worsening in some way unrelated to Valcyte.

    I also like your suggestion for trying an in-between dose. My psychiatrist and I speculated that might be helpful, but I need to run it by my CFS doc still.
     
  4. BrianD15

    BrianD15

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    I'm writing these replies in the middle of the night having awoken after only 1.5 hours sleep. I'm hoping to feel tired again soon so I can get some rest. I took some additional melatonin, but not feeling a thing yet. The funny thing is this is the most alert, energetic, and clear minded I've been all day. It's so ironic that I'm struggling to be functional in the daytime but feeling too functional when it's time to sleep.

    Followup question for zzz and others: If you're on a twice per day dosing schedule, when do you take the pills? I take my first dose between 7 am and 9 am, basically as soon as I wake up. I try to take the second dose at about 2 pm. That's not spaced out by 12 hours as I figure would be ideal - but the idea was to not take it too close to bed time. Obviously hasn't helped much.
     
  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    I dont think people really know how much it has helped them until they have finished their 6 or 12 month course. Its a bumpy ride, hold on. Most have switched over to famvir or valtrex to keep viruses down once valcyte has hammered them.
     
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  6. zzz

    zzz Senior Member

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    I agree; these are all strong signs that the Valcyte was simply acting as a stimulant.
    Valcyte is supposed to be taken with food for best absorption. Having some fat content in the food helps with the absorption of Valcyte. But there's no need to go overboard here and put lots of fat in your diet just for the Valcyte.

    On a twice a day dosing schedule, Valcyte is typically taken with breakfast and dinner. If Valcyte is well tolerated at a given dose, taking Valcyte with dinner does not interfere with sleep. I was on a dose of 900 mg a day for five years, taking it at breakfast and dinner, and Valcyte never gave me any problems sleeping. However, if the dose is too not well tolerated, then even taking just a single dose in the morning may still result in insomnia at night.
    In my experience, the results vary a lot by person. For example, both @BrianD15 and I started noticing positive effects after two weeks. I had only very minor side effects with IV ganciclovir, and I had absolutely no negative side effects when I took Valcyte at 900 mg per day for five years. The positive effects I noticed after the first two weeks continued to a greater or lesser extent the whole time I took the drug. I discontinued it without incident when it was no longer making improvements in my health.

    I understand that many people have minor or even major problems tolerating Valcyte. Once again, it just really depends on the person.
     
    Last edited: Sep 14, 2017

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