A Very Boring, Yet Very Interesting Drug Interaction

Index Support Center Forums Treating Narcolepsy A Very Boring, Yet Very Interesting Drug Interaction

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  • #7238

    attackingbutterfly
    Participant @attackingbutterfly

    I’m not dealing with Narcolepsy, but instead a distinct severe sleep issue. Given what happened though, I’m posting this in a more general area since if it reproduces this may effect nearly everyone on here.

    Sometimes drug interactions are boring. The drugs involved do exactly what they’re documented to do, yet with a small twist.

    Sometimes drug interactions are interesting. Certain drugs paired together gain new effects unrelated to anything they do by themselves.

    A drug interaction can be both when together they switch between effects and the change is huge.

    Levothyroxine:

    Levothyroxine treats variants of hypothyroidism only. Notably Primary Hypothyroidism, Secondary Hypothyroidism, Tertiary Hypothyroidism, and Peripheral Thyroid Hormone resistance. If you don’t don’t have some variant of hypothyroidism, Levothyroxine is bad. The list of adverse effects of excess Levothyroxine is huge.

    Hypothyroidism’s documented sleep effects are causing central apneas and suppressing N3 sleep. As such you would expect Levothyroxine to reduce one’s count of central apneas and promote N3 sleep.

    Levothyroxine is a stereo-isomer of the human hormone T4. The
    stereo-isomer breaks down more slowly and thus there is less variance between when doses are taken. Otherwise this is identical to a human hormone.

    GHB/sodium oxybate/Xyrem:

    GHB is well known to be a very broad spectrum prescription sleep aid. While only approved for Narcolepsy/Cataplexy, many other sleep conditions sometimes respond favorably.

    GHB has a number of effects, but two are of note for this posting. GHB is the most potent promoter of N3 sleep ever found, but GHB also causes central apneas.

    GHB is a straight out human nervous system chemical. Jazz Pharmaceuticals is attempting to deuterate Xyrem to improve it, but I suspect the greatest improvement will be in the price.

    I had a close family member heavily reporting feeling much better with distinctly more Levothyroxine than they should have. As such I wanted to try the burnt fingers approach to Levothyroxine. Simply give increasing amounts until there were signs it was too much and see whether that made any difference.

    I finally got that experience a few years ago. Turned out 75mcg of Levothyroxine made a pretty miniscule improvement. It was an improvement, but one so small as not to be worthwhile. There is no sleep test data for this point.

    At this point my sleep medicine doctor finally pulled out sodium oxybate and by pure accidental chance it overlapped with the Levothyroxine experiment. Suddenly I felt wonderful, a massive improvement. A sleep test showed 18.4% N3 sleep and 13 central apneas.

    Insert your favorite metaphor or simile here for what happened three days after the endocrinologist terminated the Levothyroxine experiment. Being hit by a bus, run over by a train, airplane crash, or choose your favorite alternative. A sleep test showed 4.5% N3 sleep and 27 central apneas.

    A baseline sleep test had shown 3.6% N3 sleep and 0 central apneas.

    If one was a researcher writing a paper, you might use the title “Thyroid and Sleep” and the paper would be about hypothyroidism has its documented sleep effects by interfering with the gamma-hydroxybutyric acid in the human nervous system.

    After that your next paper would be, new test for hypothyroidism, give the patient sodium oxybate and run a sleep test. The test result would be the quantity of N3 sleep. Less than 15% N3 sleep would be worrisome, less than 10% N3 sleep would be time to give the patient significant(ly more) Levothyroxine now.

    I imagine several of you are wondering how such a thing could be real yet no one on this site ever having observed this before. My response is easy, everything needs to line up right for you to realize what is occurring and there are several spots which can be missed.

    First, in order for me to notice what was going on you must have four very specific experiences:

    Baseline, no Levothyroxine or sodium oxybate.

    Levothyroxine without sodium oxybate.

    Sodium oxybate without Levothyroxine.

    Sodium oxybate combined with Levothyroxine.

    Miss even a single one of these and you won’t have the slightest clue they’re interacting. The three key points are semi-mutually exclusive. Most cases you end up on Levothyroxine for Hypothyroidism, at which point you’re very unlikely to ever experience sodium oxybate by itself. If sodium oxybate by itself is even mildly useful to you, you’re unlikely to give it up at which point you’ll never experience Levothyroxine by itself.

    Second, how long was the time-frame you had these over? I had them over the course of about 6 months. If you spread them out over 5-10 years or more, you may not be able to compare them and realize something interesting is happening.

    Third, how much Levothyroxine did you try? Due to keeping a sleep log I know 25mcg of Levothyroxine equates to roughly 45 fewer minutes of sleep a day. At the dose level I’m presently at there is little difference in overall level of wakefulness, so without a log it isn’t all that easy to notice differences.

    More or less I’m speculating GHB/sodium oxybate/Xyrem’s irregular behavior is not an innate characteristic, but instead an effect of irregular treatment of thyroid conditions. I’m presently attempting to get reliable access to more Levothyroxine, in order to turn me back into a fully functional person. The obvious approach is to start World War 3 of the field of Endocrinology by causing research showing the above proposed test is a better indicator of overall thyroid condition than any existing test.

    #7242
    Ferret
    Ferret
    Participant @ferret

    I would like you to provide a link which backs up your statement “GHB is the most potent promoter of N3 sleep ever found” please.

    In the following link (2018), it states that how Xyrem (GHB) works is not known… and that it does not reduce REM sleep. REM sleep is the biggest problem that those with Narcolepsy and Cataplexy have.
    http://healthysleep.med.harvard.edu/narcolepsy/treating-narcolepsy/medications

    So, if you don’t have Narcolepsy and its peculiar brain chemistry, why do you think that your combo would work. And, if you don’t have Narcolepsy, how do you have access to Xyrem?

    #7269

    attackingbutterfly
    Participant @attackingbutterfly

    I would like you to provide a link which backs up your statement “GHB is the most potent promoter of N3 sleep ever found” please.

    In the following link (2018), it states that how Xyrem (GHB) works is not known… and that it does not reduce REM sleep. REM sleep is the biggest problem that those with Narcolepsy and Cataplexy have.
    http://healthysleep.med.harvard.edu/narcolepsy/treating-narcolepsy/medications

    Simply listening to what sleep doctors say is my primary source. Citing your own reference though near the middle just under “Sodium oxybate“: “These two doses produce deep sleep through much of the night”. Note “deep sleep” and N3 sleep are referring to the same thing. Not an explicit statement that it is the most potent promoter of N3 sleep ever found, but pretty close.

    How exactly gamma-hydroxybutyrate works is mostly unknown. Much of what I’ve read suggests the promotion of N3 sleep is suspected to be why most non-narcolepsy conditions respond favorably. Almost reads like it promotes N3 sleep so strongly that N3 sleep displaces REM sleep.

    So, if you don’t have Narcolepsy and its peculiar brain chemistry, why do you think that your combo would work. And, if you don’t have Narcolepsy, how do you have access to Xyrem?

    I was told by a doctor in May, that the law written by Congress’s law states it is allowed for use with Narcolepsy or debilitating Hypersomnia. The FDA has only approved it for Narcolepsy, but many doctors of sleep medicine are willing to employ it for other severe hypersomnias. Having a MSLT result showing EDS and a REM incident is valuable (pretty sure I have non-Narcolepsy Hypersomnia; but I can take naps on Adderall).

    Knowledge of this interaction is likely to help others because what happened points towards hypothyroid-type conditions interfering with the gamma-hydroxybutyric acid in the nervous system. If this is the main reason why sodium oxybate is so inconsistent, then this will make sodium oxybate reliable. One question does come up, do gamma-hydroxybutyric acid’s therapeutic effects for narcolepsy come from properly functioning effects or from malfunctioning effects? If the therapeutic effects for narcolepsy patients is due to malfunctioning gamma-hydroxybutyric acid, then as a narcolepsy patient you actually want mild hypothyroidism (I really hope this isn’t true, but it is a nightmare which comes to mind).

    #7271
    Ferret
    Ferret
    Participant @ferret

    For the record, I wouldn’t touch Xyrem with a 10 foot pole. I’ve read far too many PWN reports on the side effects. Don’t like the price or the secrecy or the company that currently has control of it. It has gone from being ONLY for Narcolepsy with Cataplexy to for Narcolepsy without Cataplexy to, now, Idiopathic Hypersomnia?
    The article is somewhat misleading saying on the one hand that the mechanism is unknown but then stating (as you pointed out) that it produces deep sleep but then stating that it has no effect on REM.
    Talk about indecisive. Jazz has done an incredible marketing job though.
    But, hey, we are all unique and what works for one doesn’t work for another.

    #7272
    Ferret
    Ferret
    Participant @ferret

    This is the kind of study that I was asking you for…
    https://onlinelibrary.wiley.com/doi/full/10.1111/jsr.12468

    But, please note that the author has been a consultant for Jazz in the disclosures and that the study only represented 8 weeks. That’s a very fast titration and I would love to see a study for a longer period of time. I remain dubious.

    #7648

    attackingbutterfly
    Participant @attackingbutterfly

    For the record, I wouldn’t touch Xyrem with a 10 foot pole. I’ve read far too many PWN reports on the side effects. Don’t like the price or the secrecy or the company that currently has control of it. It has gone from being ONLY for Narcolepsy with Cataplexy to for Narcolepsy without Cataplexy to, now, Idiopathic Hypersomnia?

    The entire pharmaceutical industry is ethically challenged. Cures are something to deliberately avoid since you can only sell them once (you can charge a heck of a lot, but only once).

    Xyrem is not approved for idiopathic hypersomnia.
    Happens that my case responds to it, but it is not approved. I know one doctor who is okay with treating idiopathic hypersomnia with sodium oxybate and one who is not. Sodium oxybate was found to be very broad-spectrum in the 1980s-1990s before Jazz got their hands on it.

    Hypothyroidism is known to have a vast number of effects. Most or even all of those side effects of Xyrem might be due to hypothyroidism interfering with gamma-hydroxybutyric acid. What I’ve observed is likely a very big deal, yet Endocrinology doesn’t want to have their tests discarded.

    I’m certainly unimpressed with how much Jazz is charging for Xyrem.
    I’m also highly disgusted that they somehow got patents for something which was first synthesized in the 1870s. This doesn’t change the fact that it is extremely effective for me.

    The article is somewhat misleading saying on the one hand that the mechanism is unknown but then stating (as you pointed out) that it produces deep sleep but then stating that it has no effect on REM.

    All that means is sodium oxybate doesn’t help by getting rid of REM. Perhaps the additional N3 sleep is simply so beneficial as to make the excess REM sleep irrelevant.

    Talk about indecisive. Jazz has done an incredible marketing job though.

    I literally asked a doctor with skill in sleep medicine, “just throw everything at me, and we’ll see what sticks”. After a year and a half of a bunch of sleep medications, many which made things much worse we finally got to levothyroxine plus sodium oxybate. The combination was extremely valuable since I now know my case is treatable. I now also have a feeling for how much damage is being done. I no longer have any reluctance about calling my case a disability.

    Meanwhile what I’ve noticed here seems likely to greatly increase sodium oxybate’s effectiveness. Are there any adverse effects of sodium oxybate which could not be effects of hypothyroidism? The answer to that may well be “no” in which case suddenly sodium oxybate becomes a highly reliable sleep medicine.

    #7662
    Ferret
    Ferret
    Participant @ferret

    I’m very happy that you’ve found something that works for YOU. It’s always a struggle but a fight worth continuing. Congratulations.

    #7921
    TheRabbitKing
    TheRabbitKing
    Keymaster @deathrabbit

    I for one found this interesting ant not boring at all. Good post

    My current jam: Anathema - Springfield

    #7943
    Pereise1
    Pereise1
    Participant @pereise1

    I also find this to be interesting, especially since I’ve woken up with a headache from time to time after taking phenibut the night before, a sign of poor brain oxygenation. My TSH, which is not a good indicator of thyroid function, is on the borderline of low and normal. I feel like trying to get my T4 and T3 measured so as to see if maybe that’s a conmorbidity causing my piss poor sleep quality. I definitely feel that Narcolepsy has had a negative effect on my GH output. I’m sore for 3-5 days after lifting weights whereas before it was a max of 1 day of soreness. My skin feels noticeably thinner than before, and cracks more easily. And my memory sucks too, all signs of low Growth Hormone and low N3 sleep. I wonder if any other PWN have strange symptoms like that as well, and if either levothyroxine or GHB helped them with it.

    #7944

    Natdoc
    Participant @natdoc

    Pereise1
    I have never been a big believer in the current method of measuring thyroid function. Most physicians rely entirely on the results of the TSH alone. I have had patients with normal TSH,T3 and T4 levels who most definetely have a thyroiditis known as Hashimotos thyroiditis.
    Each lab has differing reference ranges for blood values so it is important to know which lab does your studies and what their reference ranges are.
    We have found that along with the TSH we need to check for T3,T4, reverse T3 and thyroid antibodies which are the most useful for predicting a thyroid disease. This is a part of our normal screening blood test as it should be for every physician.
    High antibodies indicate that a patient’s symptoms are from too little thyroid hormone regulation when the TSH, T4, or T3 fail to do so. Consider a 1996 study by Aarflot and Bruusgaard. They included 737 men and 771 women in their study. Men and women who had chronic widespread musculoskeletal pain (often diagnosed as “fibromyalgia”) had a higher incidence of thyroid antibodies than men and women who didn’t have pain. But the TSH, T4, and T3 levels of the two groups of men and women did not differ.
    research is now complete in showing that fibromyalgia symptoms are caused mainly by too little thyroid hormone regulation. In view of this, Aarflot and Bruusgaard’s finding indicates that antibody tests show too little thyroid hormone regulation while the TSH and thyroid hormone levels often fail to do so. As the well-known thyroid specialist Dr. Robert Volpé has written, the TSH, T4, and T3 levels may be “normal” for years despite patients having autoimmune thyroiditis the whole time.

    You can have more confidence in your need for thyroid hormone therapy if you have one or more of the physiological abnormalities common among hypothyroid patients. The abnormalities include (1) a low basal body temperature, (2) a basal pulse rate too low for your level of cardiovascular conditioning; (3) a slow relaxation phase during your Achilles reflex; and (4) a low voltage R wave in the QRS complex of your EKG. Of course, you can measure your temperature and pulse rate at home. Hopefully your doctor will cooperate by testing your Achilles reflex and measuring the voltage of your R wave.
    I wish you luck

    #7950

    everythingthatshimmers
    Participant @everythingthatshimmers

    I tried a small dose of levothyroxine to treat my IH but unfortunately didn’t see any improvement. Of course, I also didn’t have the benefit of the drug interaction you described.

    I’m curious about the prescribing of Xyrem for sleep disorders other than N. Is this becoming a common practice?

    #8080

    attackingbutterfly
    Participant @attackingbutterfly

    We have found that along with the TSH we need to check for T3,T4, reverse T3 and thyroid antibodies which are the most useful for predicting a thyroid disease. This is a part of our normal screening blood test as it should be for every physician.

    Therein lies a serious problem. According to the data generated by all the thyroid tests together (everything has been run on me by endocrinologists), perhaps I should have a little bit of levothyroxine. I’ve currently got an endocrinologist who is willing to be aggressive and give me enough levothyroxine to push some of the test results to their limits. Meanwhile I need roughly double that amount to be fully functional, which would push several of the thyroid tests out of range.

    If this reproduces, none of the existing thyroid tests (even as a group) properly measure how close the body is to an ideal level of thyroid hormone. Most likely there are multiple places where resistance can occur and some of those are far more common than acknowledged “peripheral thyroid hormone resistance”.

    I tried a small dose of levothyroxine to treat my IH but unfortunately didn’t see any improvement. Of course, I also didn’t have the benefit of the drug interaction you described.

    You only got 2 of the 4 experiences so you didn’t notice anything.

    I’m curious about the prescribing of Xyrem for sleep disorders other than N. Is this becoming a common practice?

    Unknown.

    The first doctor I encountered my case was still an unknown and we were speculating about it being some variation of narcolepsy, but there wasn’t any diagnosis at the time.

    The second doctor I encountered stated Xyrem wasn’t approved for anything other than narcolepsy, but idiopathic hypersomnia was severe enough that they were willing to prescribe it.

    I asked Dr Joseph Cheung of Stanford since I’m exploring the possibility of moving to the general vicinity. Dr Cheung said he had prescribed Xyrem for idiopathic hypersomnia in the past, but was unwilling to prescribe it now.

    Seems a case of “you pay your money and take your chances”. Since becoming fully treated will have several large companies offer me quite a bit of money to relocate I’m preemptively exploring doctors in the Bay Area.

    I’ve got no idea whether the number willing to prescribe is increasing or decreasing. I’m guessing the percentage is staying roughly stable and likely about 50% are willing. Doctors are trained to sympathize with patients and idiopathic hypersomnia is a severe diagnosis.

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