Vyvanse/Elvanse lasting only 4-5 hours, only low doses of ADHD medication tolerated

ADHD - medical, neurological, therapeutic Medication of ADHD*
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Hi out there, anyone got similar experience?

First, I tried methylphedidatehycrochloride (MPH). 5mg sustained-release capsules were almost OK but I was overdosed with 10mg. I prepared 7,5 mg capsules and felt fine.

But then I got allergic symptoms so that my psychiatrist prescribed Vyvanse.

Vyvanse/Elvanse 30 used to be the lowest available dosage for adults in Germany until recently.

I was overdosed with 30mg and then after 5 hours I hardly felt any benefit any more.

Now I take 15 mg in the morning and 10 mg after 4-4,5 hours. That’s fine but after 4 hours it is over again.

So my psychiatrist prescribed Attentin for the afternoon and early evening.

"Dexedrine“, „ProCentra“ or „Zenzedi“ should be the equivalents in the US according to the German version of Wikipedia.

Attentin is not reimbursed for adults so I have to pay on my own.

As my daily dosage is very low, it is OK for me.

But if I am asked about the dosage of my ADHD medication and say I take Elvanse 15mg - 10 mg and then 1,875 mg at 2 p.m. and at 5 p.m., doctors frown at me and don’t take me seriously anymore.

I am very uncomfortable with this situation…

I had my metabolic enzymes checked but nothing special about CYP2D6.

I’m intermediate metabolizer for CYP2B6, CYP2C19 and TPMT.

Anyone any clue?

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Your therapist’s dosing strategy is just making things worse.

[Disclaimer, I have no professional credentials. Just got fed up and desperate and spent a few hundred hours researching various topics online. And jaded that all relevant info for my medication approach and issues is tied up in research and not known by therapists. I.e. Again, no professional credentials, but do have a lot of opinions. And don’t have all the links to everything which makes it harder to verify content]

But first,
Vyvanse, you can open the capsule and take a portion of the medication with something like applesauce if the dose is too high. They open the capsule and kids take it this way if they can’t swallow capsules. You can buy empty capsules online at Amazon.com or I’m sure you could find other places that sell them. Can put the unused portion in there. DO NOT CRUSH OR CHEW THE SPANSULES FROM THE CAPSULE. Can also buy scales on line and weigh a specific dose that way. But need to base it on fraction of total weight of capsule contents since the dose only represents the active ingredient, not all the other ingredients with it.

Second, do a search of the forum for memantine and strattera. Should find another response I made that mentioned how memantine or strattera can potentially reduce your amphetamine tolerance over time. I also mentioned that generic brands can be any where from therapeutic to useless. So go back and check that you are getting the same brand as what was effective to begin with. I don’t know the generics market in other countries. But in the U.S. it sucks with most amphetamine based meds generics being useless garbage. And the FDA and DEA in denial. GRRRRRR

Third, in the U.S.A Dexedrine Spansules is extended release dextro-amphetamine. They discontinued immediate release Dexedrine IR. In which Zenzedi took over that space and is now the name brand immediate release replacement for Dexedrine IR. generic Dexedrine spansules is called Dextroamphetamine ER or dextroamphetamine spansules and generic Zenzedi is dextroamphetamine IR.

It sounds like maybe your brain rapidly downregulates from the medication. But, that is just a guess. Or you are a very fast metabolizer. Genetic tests are not definitive. For things like this they just say what propensity you have, which is not absolute. You can still be a fast metabolizer. Can also take a blood test so see if your urine is unusually acidic which eliminates amphetamine faster.

If amphetamine based meds start off too strong in the morning and wear off very fast, it is the wrong drug for you to be on. Unless you tried everything else and they were worse.

This link I post below explains the role of “acute tolerance” and the effect on doses of MPH and Adderall IR. Explains the dosing strategies based on acute tolerance which went into consideration in the design of Concerta and Adderall XR. And, since Vyvanse is amphetamine, it applies to that also.

Our brains naturally try to counteract exogenous changes, like meds that change our neurotransmitter levels. It does this by shutting down receptors, which reduces the receptor density, and reduces the effectiveness of the level of neurotransmitter in the synapse (Have to at least understand what a synapse is to understand so may need to look that up if not familiar). Which means, your “therapeutic dose” starts to change right away and decreases during the day as more receptors shut down. The amount of active pharmaceutical ingredient (API) has to be above the minimum therapeutic threshold at any given time of the day to be effective.

These downregulated receptors require the API to be low and out of our system long enough for our brains to upregulate those receptors back into play. If not able to upregulate all of them, after a while they get permanently removed (replacements can be made but need to be off the drug for an extended amount of time), which is one route to long term tolerance and dosage escalation.

So, as an example, Adderall IR, recommended to take second equivalent dose 4 hours after first. Which nearly doubles the Blood API Concentration (BAC) just to maintain the same therapeutic effect as during the morning for the afternoon. Otherwise it wears off too fast. And the BAC level in the afternoon that it feels like it is wearing off, can actually be higher than that BAC level that was great to start your morning off with.

For most people with a proper vyvanse dose, it should be effective I think 10 to 14 hours. In which they try to account for acute tolerance issues in the design.
Quick explanation of Vyvanse. Forget the “prodrug” aspect. It is a gimmick and done because they get better patent protection by modifying the base molecule than they do with simply changing the release rate. So, they could have skipped adding a lysine molecule onto the D-amphetamine molecule and not had an hour delay for it to start working.
It is the long slow extended release that is important. Which there is a lot of confusing info about online. Vyvanse is preferred due to its lower occurrence of side effects and less chance of causing tolerance than other amphetamine meds. This is because the long sustained release method results in a much lower peak BAC curve and having a lower BAC curve means less side effects, less acute tolerance, and less long term tolerance.

Also, vyvanse converts to less than half its dose into the actual therapeutic ingredient d-amphetamine. So, 70mg results in about 30mg actual D-amphetamine, and spreads out the release over many many hours keeping peak BAC a fraction of Dexedrine, Zenzedi, Adderall IR or XR, etc.)

By adding other amphetamine based products with a much higher peak BAC curve, that causes faster and more acute tolerance. By having that later in the day, you are just keeping the API in your blood stream too long and not having time with it out of your bloodstream to upregulate those receptors for the next day. Even worse, may be enacting the other ways amphetamine can cause tolerance which are harder to get back under control. And the worst of all, when your amphetamine tolerance is too high, no other ADHD medication would be therapeutic at any prescribable level. So, won’t be able to switch meds, be stuck on amphetamines, which would likely be ineffective in a short time at the max dose since it looks like dosage escalation is a problem for you. I’ve already been down that road and it sucks.

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Hi,

Thank you very much for your detailed answer :slight_smile:
You’ve mentioned some exciting things that make me curious…

Do you have a source for that? That would be news to me.
I only know something like this about Concerta (OROS); this does not deliver the entire contents, which is why the figures for the doses are so crooked. I wouldn’t know that about lisdexamfetamine. I would be very curious about that.

Swanson was, as far as I remember, the only one who advocated this theory of acute tolerance. According to my memory, there were later studies that could not reproduce / confirm this. But I would have to dive very deep to find that again.

What influence does memantine or atomoxetine have on preventing the development of tolerance to amphetamines? I would also be very interested to know which mechanism that would be.

According to ADxS surveys, a single dose of Vyvanse works for less than 7 hours in more than 60% of those affected, although this also relates to European data. Is the experience in the USA really that different?

Looking forward to reading from you…

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Sorry for the late response.

The survey should be considered with a not so accurate set of data. People self reporting is not always that accurate. In the survey you don’t know exactly what each individual considers as their duration. Might still be effective, just not as sharp as when it kicked in earlier. It’s a survey, not a controlled study. And it is for people who are not new to the drug. The manufacturer data is based on people new to the drug. If I recall, EU does dosage by weight of person? What do they do about tolerance? The U.S. the dose is adjusted by how well it is still working or not. Weight, is only a factor for younger children.

I have seen several sources in regards to the amount of dex left after lysine is cleaved from dextroamphetamine. I do know off the top of my head the page for amphetamine on Wikipedia has it. Can check the source referenced on there for more details. Also seen studies comparing the absorption/elimination curve for dex in the blood that had dex vs the lisdex dose with equivalent conversion to dex.
Personally I think the amphetamine wiki page has a lot of biased cherry picked sources and some topics are pretty bad. But, this chart is in line with other sources I’ve seen. shows 74.2 mg lisdex is on par with 30 mg of what would be zenzedi (100% dex)
Amphetamine - Wikipedia mg,-amphetamine%20base%20suspension

I’ve never seen anything say the concerta OROS did not deliver the entire active ingredient. I do know part of the pill is just a container for it. What do you mean by the figures for the doses are crooked? By comparison to lisdex or something else?

This article shows the dosing strategy of Ritalin and Adderall IR, as well as design of concerta OROS and Adderall XR…..all based on the effects of acute tolerance. Literally chart how it moves the therapeutic curve during the day which is why we have our dosing strategies and extended release designs. Literally, acute tolerance (although was referred to as the opponent process and receptor downregulation at the time) was taught in my psych 101 course in 1999. There is a lot of shady research in relation to amphetamine meds in my opinion. I’d take a look at some of the research you have seen and see if any researchers had pharma affiliation or if the drugs were supplied by or if study was funded by pharma industry. Seen enough misguided research with pharma involvement concluding things convenient for industry, not for patients.

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Says I can only put 2 links because I am new, so breaking up the response.

Doing a quick search online, seems “acute tolerance” may be defined differently by different people which may make it hard to agree on things. Receptor downregulation I mentioned is not the only way it happens, just easy to understand part of it. Not an expert so I don’t absorb all the different things I read on the subject. Just the stuff important for my own issues. Which may just be the higher level summary, with the knowledge that I can dive deeper again if needed to. Here some searches that highlight aspects of acute tolerance, even if not searching for that specific name, with Google AI enabled (for convenience). Granted, shows up as boxes with what looks like maybe German I can’t read on my screen with the links. When I click on them, they take me to the different searches even if it has the same text, maybe warnings?

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I had forgotten this term but there it was again. Link is a search on the term with Google AI enabled (for convenience). You’ll see it is “acute tolerance”.
tachyphylaxis

From this wiki page:
”Tachyphylaxis …is a medical term describing an acute, sudden decrease in response to a drug after its administration (i.e., a rapid and short-term onset of drug tolerance).[1] It can occur after an initial dose or after a series of small doses. Increasing the dose of the drug may be able to restore the original response.”

Now, if you read the article I posted on dosing strategies and extended release drug design of Ritalin/concerta, Adderall ir/XR, you will see how the above paragraph fits. It mentions the rapid onset of tolerance. then reads “Increasing the dose of the drug may be able to restore the original response.” Literally, for example, with Adderall IR, the official dosing strategy is to take an equal dose 4 hours later, just to maintain the relatively same therapeutic effect as it did in the morning, for the afternoon. And the BAC curve shows a nearly doubling of the blood concentration, just to maintain equal therapeutic effect.
Literally, official therapeutic drug dosage strategies and drug design for ADHD meds is based on the study of the effect of acute tolerance and the resulting change in therapeutic curve that occurs from it. So, when I hear actual doctors (MD or PhD) talk about not finding proof of acute tolerance, knowing billion dollar drug industry is based on it, raises some red flags. (In case it didn’t come through, agro sarcastic response is in no way direct toward you, but my frustration with all the related industries and services that make me constantly go WTF? which makes it so difficult people like us, looking for real answers. )

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Absolutely right, that is a clear limitation..
On the other hand, it guarantees that data collection is not influenced by the pharmaceutical industry :wink:
But result is quite similar to what we experience in the German-language forum (unlike this one, we have a lot of traffic there, several thousand members, and currently 160k unique readers per month).
And it is extremely important for people with ADHD when they are denied daily coverage because manufacturers’ specifications have turned theoretical values into a normative standard that cannot be achieved in practice.
That’s why I try to look at it with an open mind.

Perhaps that is the more decisive difference. In my opinion, it is the long-term practice that matters, not the effect on the first day or in the first few days.
Meanwhile, doctors here are also realizing that the manufacturer’s information on the duration of action of lisdexamfetamine is often longer than what they experience with their patients.

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In Germany, dosage based on weight is not an issue. Weight is only taken into account for upper limits for MPH in children, as a warning signal that a doctor needs to take a much closer look. Weight plays no role at all with LDX. I am not aware of this being any different anywhere else in the EU.

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Thank you for your search suggestions. A German source said, translated into English here:

“Tachyphylaxis is a rapid form of tolerance development to certain drugs. For example, the reuptake inhibition of neurotransmitters leads to a gradual depletion of the presynaptic transmitter stores.”

I am fully aware that tachyphylaxis, also known as acute tolerance, exists in pharmacology. I would just like to point out that, with the exception of Swanson et al., who are also cited on the Wikipedia page for MPH, there is no specialist literature on ADHD medication. What there is in abundance is general literature on amphetamines. However, this refers to amphetamine in drug doses and, in my opinion, is simply transferred to amphetamine medications without any critical questioning.

With ADHD medications, I would not administer multiple doses of the same amount on the same day - especially if the goal is to maintain a consistent blood level. Even with MPH, a certain level remains in the blood after the subjective effect has worn off, which simply needs to be replenished in order to return to the therapeutically effective range. This applies even more to amphetamines, which have a significantly longer half-life.
And 4 hours for amphetamine seems a little short to me – I would have expected 5 or 5 1/2 hours. But amphetamine salts (Adderall) are not available here. Is 4 hours the normal habit in the USA with Adderall?
In the practice of the German forum, most of those affected who take several doses a day get by with lower follow-up doses. However, there are also cases (albeit very, very rare) where someone needs increasing doses. The vast majority, however, clearly use decreasing doses. And if you are concerned about acute tolerance, I think this is also a sensible approach.
I stumbled across a specialist article a few days ago that said follow-up doses should generally be lower – but as I had a three-digit number of studies open, I have no idea where that was.

This I saw too late - but it hits exactly the same note that I just struck.

Since ADxS is funded entirely by small donations from readers and has no ties to the pharmaceutical industry, I think we’re pretty safe when it comes to the risk of industry influence.

I’ll get into this later again, and read your posts again more carefully.

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Ah, sorry, I misunderstood.
Yes, one mg of lisdexamfetamine is less mg of dextroamfetamine.
50 mg lisdexamfetamine dimesylate (equivalent to 28.9 mg lisdexamfetamine) is equivalent to 14.8 mg dexamfetamine.

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lisdexamfetamine dimesylate is the chemical name but lisdexamfetamine should be the same thing, just the generic drug name. To the best of my understanding. Generic drug may list the generic drug name or the chemical name.

But, I am pretty sure there is also an extended release component to the marketed drug. Because earlier studies proved lisdexamfetamine readily metabolized to dex. Graph of 100% dex vs lisdexamfetamine that converts to equivalent dex, exact same curve about an hour apart. Same peak blood concentration etc. Yet the marketed drug has longer drawn out release and much lower peak blood concentration. Some studies say it is the lysine being cleaved off that takes time and why it has extended release. Which contradicts earlier studies proving the conversion happens rapidly once absorbed. But, there may be something I am missing that explains the contradictions. Till then, I have my own thoughts on it….

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don’t get me wrong, the survey has good information that is highly relevent to patients, prescribers and industry. And avoiding industry bias is great. Just need to keep in mind human bias and going by “feel” rather than less error prone cognitive testing at different times has. Also, I don’t know about Germany and Europe, in the U.S. it is very common for someone to start with a dose that is too high (in my opinion) and mistake the initial euphoric effect for therapeutic. Which may skew results. Again, that is in U.S., don’t know if it applies. U.S. common talking points is “Medication side effects may be strongest at first, but in a week or 2 you will get used to the medication”. Which I say downregulation and damage till the dose is no longer too strong is a great marketing approach for drug companies who came up with the talking points. Starting with mild dependence keeps them coming back for more and not having so many days off.

I agree, it’s the long term that matters. But the drug maker limited research to 6 weeks or less. Because it costs money they didn’t need to spend to get to market. And it would expose long term side effects that they would have to list. The official FDA prescriber documentation for Adderall IR, basically says long term studies over 6 weeks have not be done and it is up to the prescriber to determine if they should continue or not. Drug company managed to put it all on the therapist, without indicating long term issues that may arise, or any more info.

Originally the recommendation was to dose with smaller dose later. Which they found not to be fully effective. Which is why they changed the strategy like 20 years ago to equivalent doses. Based on actual research showing the therapeutic curve changes during the day due to acute tolerance. It may mean a lower initial dose compared to what others in Germany are used to starting with to make it longer in the day. The article I linked with the actual research all that is based on explains it pretty well. The earlier link “Long-acting stimulants:development and dosing”. Shows they did try different strategies and the equal dose separated was best for Adderall and XR mimics it. For methylphenidate IR (Ritalin) with shorter half-life, 2 times was typical but 3 times not unusual. OROS, for concerta strategy of extended release, could be wrong but think it was like 3 times a day with the peaks smoothed out. But been a while since I read that section.

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I would definitely spend a lot of time with the article I linked on dosing strategies and how acute tolerance shifts the therapeutic curve in the afternoon.

I made the mistake of trying to take a large dose that lasted as long as I needed it as I did not know all this at the time. higher peak BAC means faster downregulation and potential damage and side effects. Later, after using Strattera to reduce my tolerance, took 40 in the morning and 0, 10, or 20 depending on how I felt in the afternoon and tried to take the least effective dose I could get by on. Due to very susceptible to damage and downregulation and accumulating side effects that ruined my life (not an exaggeration). Note, ADHD with comorbid SCT and narcolepsy is the perfect setup for dose escalation but I’ll skip getting into that now.

Now, I do also have a lot of coping mechanisms as I was almost done with my 4th college degree at age 32 when I was finally diagnosed with ADHD. Had no help and relied only on myself to make it through college and 3.5 years as an IT consultant till then. Started college at 23 after midlife crisis. Coping mechanism plus stuff I learned from a general study of psych degree with a lot on the side of cognitive science. And eventually working from home full time especially helped, before my life imploded. If I get time I’ll post my in process and very poorly written study tips that others may benefit from. not comprehensive, but may be helpful to some.

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Revisiting the meds wearing off too fast issue.

  1. Brain can adapt to the expected stimulation level of medication and start to let the “noise” through again. In which case the meds are still working. Best option would be the non-drug therapies to try to manage the gap before trying a higher dose (assuming the dose worked before, and not that the patient hadn’t titrated to their effective dose yet).

  2. Tolerance in general, person may build tolerance either naturally or due to not optimally managing their medications and other routines like getting enough sleep and eating right, etc.
    Or if they were started on a dose that was too strong with side effects at first, and was told they would get used to it in a week or 2. Which just causes enough tolerance so that it is no longer too strong. But, increases the chance for more tolerance being above their optimal therapeutic dose. Hopefully people reach a stable steady state instead.

  3. Acute tolerance being over triggered. Vyvanse is made to avoid triggering acute tolerance. Doesn’t spike BAC levels, flattens out the BAC curve. So, when titrated and responding right, should last 10 to 12 hours or so. Some people, especially slow metabolizers, have found that even Vyvanse can trigger acute tolerance resulting in it not lasting as long. (Refresher: that whole shutting down receptors so when BAC drops, there are no longer enough receptors to support BAC levels and it feels like it wore off too soon.) In which case some have found taking half the Vyvanse dose separated by 4 hours or so flattens the curve enough to avoid acute tolerance, without end of day crash or building long term tolerance. Or some just reduced their dose which may have been too strong while causing the opponent process acute tolerance issue.
    Now, some people even on other drugs have more acute tolerance and feel like it wore off faster. This has happened to be more recently. Got my meds to work better by taking a little more and managing other factors. But wore off faster. Yet, partially functional even further from therapeutic dose has me going for 15 to 20 hours straight making even worse than usual posts on social media.

  4. Don’t know. Does Germany or Europe in general have the same issues as the U.S. …crap generics that do not work right? If Germany has generics that struggle to cross the BBB, can explain why it would wear off sooner. Basically like being underdosed. U.S. has people going nuts on Adderall IR/XR, Vyvanse, Dexedrine, zenzedi, and the methylphenidate meds (not as bad as amph with the BBB issue, but still an issue)
    Starting on a crap generic can also have it wear off faster than it should, and not as effective. Basing dose by weight is useless if one brand has 35% of the API crossing the BBB while the brand name reference has 90%. (just made up example figures for effect.)

Getting switched from a God brand to a bad brand, can be so bad the bad brand still has a person dependent on the meds feeling crashed out and they aren’t doing anything for them.

Personal Example. 40 mg CorePharma old formulary, Take in bed, role over kicks in 20 minutes later, get up and drive to work. Work 10 hours, manage the low points by going for a walk and what not. Drive home. 140 mg Aurobindo. Take 100 mg IR. Role over and go to sleep for 2 more hours. Alarm goes off. Take 40 mg more, go downstairs and start work. Working from home, half as effective, take a nap by hour 4 to 6 on the couch. Make up the time at night or on the weekend. Enjoy the ramped up peripheral side effects as the absorption thing is there, just not crossing the BBB. That is over an 80% variance.

Problem is the excipient profile affecting the ability to cross and / or stay across the BBB. FDA bioequivalence already proved absorption / elimination rate equivalence. Assumes therapeutic equivalence although never actually tested for it. Which is why they keep being made and given to people who are told they are equivalent with no legit explanation by the “experts” and “professionals” who are supposed to be reliable for information. (Big Pharma in the U.S. supplied talking points and narrative, made misinformation the guidelines and education of prescribers. The FDA’s head up their ass made everyone believe generics are equal while not telling them they dropped therapeutic equivalence testing in the 1980s. And ignore the BBB for psychoactive meds. While putting gout guidelines for certain meds instructing pharmacists that they can’t substitute certain meds generics for another because for critical medications, it is not acceptable. Indicating there is a difference between meds and the excipients make a difference. (like nitroglycerin heart medication, insulin, thyroid meds have groups that can be substituted within, etc.)

  1. Adderall wearing off in 4 hours might be the right way? U.S. tends to dose people too high from the start. Single dose Adderall IR is expected to last 4 to 6 hours. If it was therapeutic before then, it is the right dose. Which is why they have the BID dosing strategy. I did do what Germans do and take a lower dose in the afternoon to get me through the rest of the day. But, would have been better off taking a lower dose in the morning, and an equal dose sooner in the day. Triggered stronger acute tolerance effects due to the higher BAC spiking in the morning. Was actually worse as I had tried to do single dose to last the day. I knew about the opponent process receptor downregulation as it was taught in psych 101 in 1999. But, did not yet understand the shifting of the therapeutic curve and just how rapid and strong it was each day. Was worried the second dose would keep me up as I naturally had sleep issues. And SCT made the dose that wore off hours before therapeutic again, making things worse. Lower over all dose divided in 2 would have had a lower BAC level in the evening, while working better and not triggering more tolerance and side effects with the higher BAC spikes.

Started decent, but meds started wearing off early writing this reply.

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Shure, but it depends, we’ve also Volks (Germany) which have a better day with the generic.