8 ms·

> The only thing I had to deal with it slightly is my Ritalin...only so slightly I can "normally" focus for an hour. I just hope things go right in the rest of

> The only thing I had to deal with it slightly is my Ritalin...only so slightly I can "normally" focus for an hour. I just hope things go right in the rest of my life. Talk to your doctor, there have been many advances in ADHD meds and they all work differently on different people. Some people respond well to Ritalin, Some respond well to the generic. Some respond well the Adderal, or Vyvanse. For some people only the name brand formulation works. Some people any formulation works. Also, make sure you are at the right dosage. You can and do build up a tolerance over time. I try to take weekends off when I don't have anything in particular I need to do, and at least one or two weeks a year (normally when I go on vacation).

fnord77 6y ago
> there have been many advances in ADHD meds respectfully, I disagree with this. The last new therapy was atomoxetine, which is almost 20 years old now and not seen as terribly efficacious. Everything else new has been some variation on mixed dextroamphetamine/amphetamine salts or methylphenidate. Vyvanse is just a pro-drug for dextroamphetamine. The only novel thing in the pipeline is SPN-812, which may work similar to atomoxetine.
- garmaine 6y ago
  New formulations are advances. I'm on Vyvanse and it has way fewer side effects than other amphetamine formulations. I could see someone deciding meds are not for them based on side effects or short duration and the come-down lows, and then have those go away entirely by taking Vyvanse.
- AnthonBerg 6y ago
  Lisdexamfetamine is profoundly different than other variants of amphetamine in utility and experience. It’s not just a prodrug – it has a rather clever molecular time-release mechanism. It comes in very slowly over a period of two hours, with plasma concentration plateau of two more. This makes a big difference; I experience no cravings or drug-seeking for more of the drug at any point. It’s also less of a “jolt”; The slow, steady increase in effect is much more conductive to steady yet limber focus. It’s just incredibly functional medicine. Also, the description of a 14-hour effective duration is accurate in my experience. It’s definitely a relatively new development and a much more humanely effective drug than previous options. — It is dextroamphetamine, which I’m inclined to believe is the more useful handedness. Levoamphetamine has more “body” effects. To the dextroamphetamine is bound a lysine molecule, and this together is an inactive powder. Enzymes in red blood cells are needed to cleave the lysine off and activate the dextroamphetamine. I’m quite certain that the dopamine rate-of-change detection mechanisms in the central nervous system cause very different behavioral and cognitive pattern cascades when it’s an almost imperceptively slow change, compared to an unhindered uptake of free amphetamine. Compare the difference in addiction potentials between faster and slower routes of administration of, say, nicotine - smoking fast, patches slow.
  - gavinray 6y ago
    > Lisdexamfetamine is profoundly different than other variants of amphetamine in utility and experience. It’s not just a prodrug – it has a rather clever molecular time-release mechanism I'm not sure how much truth there is to this claim. As you mentioned, Lisdexamfetamine is just Dextroamphetamine bound to the amino acid, l-Lysine. Once your stomach cleaves the l-Lysine, it yields free-floating D-Amp. This mechanism of action isn't any different than most formulations of extended-release Dextroamphetamine, like Dexedrine ER spansules. Additionally, Adderall and other standard mixed-isomer amphetamine salt formulations are a 75/25 mix of D-Amp/L-Amp, and the peripheral nervous system stimulation that L-Amp produces at that kind of dose (5mg for a 20mg pill) I would think to most wouldn't feel very noticeable at all. Having gone through Adderall IR, Adderall ER, Vyvanse, and Dexedrine IR over the years, to me they all felt more or less the same (besides IR vs ER). If for whatever reason Vyvanse happens to work better for some people, that's fantastic and more power to you, but the hype behind this is all marketing IMO. And, it's absurdly expensive without insurance. It was the difference between $250/mo and $20/mo using Good Rx between generic Adderall/Dexedrine and Vyvanse.
    - AnthonBerg 6y ago
      > Once your stomach cleaves the l-Lysine, it yields free-floating D-Amp. This is incorrect. – With all due respect! The action is enzymatic, and the enzyme is in red blood cells. It is slow. This is not the same as other “mechanical” time-release mechanisms. https://en.m.wikipedia.org/wiki/Lisdexamfetamine https://en.m.wikipedia.org/wiki/Lisdexamfetamine
      - gavinray 6y ago
        Sure, technically, but read the FDA paper on it's pharmacokinetics. Smoking, shooting, or squirting it up your ass won't do the trick. But injecting it would put it in direct contact with red blood cells, and so would rectal administration via absorption through rectal mucosa. Lisdexamfetamine needs to pass through the GI tract where there's proper enzymatic activity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805701/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805701/ "The environment in the rectum is considered relatively constant and stable and has low enzymatic activity in comparison to other sections of the gastrointestinal tract. In addition, drugs can partially bypass the liver following systemic absorption, which reduces the hepatic first-pass effect." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898170/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898170/ "Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. .... LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon" "The intact prodrug, LDX, was readily absorbed from the GI tract after oral administration, with relatively high levels of LDX detected in the portal blood of rats. When LDX was perfused into isolated segments of rat duodenum, jejunum, and ileum, it was absorbed into the systemic circulation; however, LDX was not absorbed during perfusion into colonic segments. These findings indicate that absorption of LDX occurs via carrier-mediated transport in the small intestines and are consistent with the physicochemical properties of LDX (ie, high aqueous solubility of greater than 0.85 g/mL within the physiologically relevant pH range of 1 to 812 and low lipophilicity [logP–1.75, unpublished data]), which would predict poor passive diffusion across biologic membranes" But hey, here I am arguing on my weekend about why exactly putting a certain amphetamine prodrug up your ass won't work. What are we doing with our lives?
- popinman322 6y ago
  There was also some work on repurposing fasoracetam for individuals with glutamate receptor issues, though I think they started with teens instead of adults. [0] For a 2019 review of novel molecules, see [1]. [0]: https://www.nature.com/articles/s41467-017-02244-2 https://www.nature.com/articles/s41467-017-02244-2 [1]: https://doi.org/10.1080/14737175.2019.1628640 https://doi.org/10.1080/14737175.2019.1628640
- LordFred 6y ago
  > The last new therapy was atomoxetine, which is almost 20 years old now and not seen as terribly efficacious. I think it's more that it doesn't work for as many people as does stimulant medication. But while it works on fewer people, for those that it does work on (myself and my partner included), it's very effective.
AuryGlenz 6y ago
Speaking of tolerance, I really wish there was an “antidote” that could be taken at night. It would encourage better sleep and I would think would help fight tolerance a ton. I take stimulants for idiopathic hypersomnia and I know things are a bit different for ADD folks, though.

fnord77 6y ago

> there have been many advances in ADHD meds respectfully, I disagree with this. The last new therapy was atomoxetine, which is almost 20 years old now and not seen as terribly efficacious. Everything else new has been some variation on mixed dextroamphetamine/amphetamine salts or methylphenidate. Vyvanse is just a pro-drug for dextroamphetamine. The only novel thing in the pipeline is SPN-812, which may work similar to atomoxetine.

garmaine 6y ago
New formulations are advances. I'm on Vyvanse and it has way fewer side effects than other amphetamine formulations. I could see someone deciding meds are not for them based on side effects or short duration and the come-down lows, and then have those go away entirely by taking Vyvanse.
AnthonBerg 6y ago
Lisdexamfetamine is profoundly different than other variants of amphetamine in utility and experience. It’s not just a prodrug – it has a rather clever molecular time-release mechanism. It comes in very slowly over a period of two hours, with plasma concentration plateau of two more. This makes a big difference; I experience no cravings or drug-seeking for more of the drug at any point. It’s also less of a “jolt”; The slow, steady increase in effect is much more conductive to steady yet limber focus. It’s just incredibly functional medicine. Also, the description of a 14-hour effective duration is accurate in my experience. It’s definitely a relatively new development and a much more humanely effective drug than previous options. — It is dextroamphetamine, which I’m inclined to believe is the more useful handedness. Levoamphetamine has more “body” effects. To the dextroamphetamine is bound a lysine molecule, and this together is an inactive powder. Enzymes in red blood cells are needed to cleave the lysine off and activate the dextroamphetamine. I’m quite certain that the dopamine rate-of-change detection mechanisms in the central nervous system cause very different behavioral and cognitive pattern cascades when it’s an almost imperceptively slow change, compared to an unhindered uptake of free amphetamine. Compare the difference in addiction potentials between faster and slower routes of administration of, say, nicotine - smoking fast, patches slow.
- gavinray 6y ago
  > Lisdexamfetamine is profoundly different than other variants of amphetamine in utility and experience. It’s not just a prodrug – it has a rather clever molecular time-release mechanism I'm not sure how much truth there is to this claim. As you mentioned, Lisdexamfetamine is just Dextroamphetamine bound to the amino acid, l-Lysine. Once your stomach cleaves the l-Lysine, it yields free-floating D-Amp. This mechanism of action isn't any different than most formulations of extended-release Dextroamphetamine, like Dexedrine ER spansules. Additionally, Adderall and other standard mixed-isomer amphetamine salt formulations are a 75/25 mix of D-Amp/L-Amp, and the peripheral nervous system stimulation that L-Amp produces at that kind of dose (5mg for a 20mg pill) I would think to most wouldn't feel very noticeable at all. Having gone through Adderall IR, Adderall ER, Vyvanse, and Dexedrine IR over the years, to me they all felt more or less the same (besides IR vs ER). If for whatever reason Vyvanse happens to work better for some people, that's fantastic and more power to you, but the hype behind this is all marketing IMO. And, it's absurdly expensive without insurance. It was the difference between $250/mo and $20/mo using Good Rx between generic Adderall/Dexedrine and Vyvanse.
  - AnthonBerg 6y ago
    > Once your stomach cleaves the l-Lysine, it yields free-floating D-Amp. This is incorrect. – With all due respect! The action is enzymatic, and the enzyme is in red blood cells. It is slow. This is not the same as other “mechanical” time-release mechanisms. https://en.m.wikipedia.org/wiki/Lisdexamfetamine https://en.m.wikipedia.org/wiki/Lisdexamfetamine
    - gavinray 6y ago
      Sure, technically, but read the FDA paper on it's pharmacokinetics. Smoking, shooting, or squirting it up your ass won't do the trick. But injecting it would put it in direct contact with red blood cells, and so would rectal administration via absorption through rectal mucosa. Lisdexamfetamine needs to pass through the GI tract where there's proper enzymatic activity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805701/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805701/ "The environment in the rectum is considered relatively constant and stable and has low enzymatic activity in comparison to other sections of the gastrointestinal tract. In addition, drugs can partially bypass the liver following systemic absorption, which reduces the hepatic first-pass effect." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898170/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898170/ "Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. .... LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon" "The intact prodrug, LDX, was readily absorbed from the GI tract after oral administration, with relatively high levels of LDX detected in the portal blood of rats. When LDX was perfused into isolated segments of rat duodenum, jejunum, and ileum, it was absorbed into the systemic circulation; however, LDX was not absorbed during perfusion into colonic segments. These findings indicate that absorption of LDX occurs via carrier-mediated transport in the small intestines and are consistent with the physicochemical properties of LDX (ie, high aqueous solubility of greater than 0.85 g/mL within the physiologically relevant pH range of 1 to 812 and low lipophilicity [logP–1.75, unpublished data]), which would predict poor passive diffusion across biologic membranes" But hey, here I am arguing on my weekend about why exactly putting a certain amphetamine prodrug up your ass won't work. What are we doing with our lives?
popinman322 6y ago
There was also some work on repurposing fasoracetam for individuals with glutamate receptor issues, though I think they started with teens instead of adults. [0] For a 2019 review of novel molecules, see [1]. [0]: https://www.nature.com/articles/s41467-017-02244-2 https://www.nature.com/articles/s41467-017-02244-2 [1]: https://doi.org/10.1080/14737175.2019.1628640 https://doi.org/10.1080/14737175.2019.1628640
LordFred 6y ago
> The last new therapy was atomoxetine, which is almost 20 years old now and not seen as terribly efficacious. I think it's more that it doesn't work for as many people as does stimulant medication. But while it works on fewer people, for those that it does work on (myself and my partner included), it's very effective.

AuryGlenz 6y ago

Speaking of tolerance, I really wish there was an “antidote” that could be taken at night. It would encourage better sleep and I would think would help fight tolerance a ton. I take stimulants for idiopathic hypersomnia and I know things are a bit different for ADD folks, though.