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Heyup,

I'm taking Vyvanse for my 20+ year treatment-resistant depression and it's working better than anything I've ever tried (the bad news is that the last 3-4 days it's losing its potency and/or taking longer to kick in, but that's another story). 

I am asking about its variable effectiveness since I also found it to vary even when it was still potent. E.g. Monday my mood would be 6/10 depression (10/10 is best mood) then Tues 4/10 then Weds 7/10. 

Anyone know why this variability happens? Anyone got any tips?

FTR I'm on 150mg Brand Lamictal, Abilify 5mg, 15mg Percocet (for chronic pain), 60mg Vyvanse, 36mg concerta (since the Vyvanse lasts 8 hours max), 20mg Omeprazole (for NERD, GERD's geeky cousin), 100mg trazodone (for sleep), 300 ranitidine (for NERD). I take the meds at the same times every day.

Many thanks!

Pete

 

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One theory I have is that you are taking both Vyvanse and Concerta together. Because of their mechanisms of action, they could be fighting each other and canceling each other out.

While dextroamphetamine (what lisdexamfetamine metabolizes into) and methylphenidate are predominantly dopaminergic drugs, their mechanisms of action are distinct. Methylphenidate acts as a norepinephrine-dopamine reuptake inhibiter (NDRI), while dextroamphetamine acts both as a norepinephrine-dopamine releasing agent (NDRA) and reuptake inhibitor (NDRI). Methylphenidate's mechanism of action in the release of dopamine and norepinephrine is different as it is thought to increase neuronal firing rate, whereas dextroamphetamine reduces firing rate, but causes monoamine release by reversing the flow of the monoamines by causing the monoamine transporters to act in reverse (instead of taking neurotransmitters out of the synapse, they bring them back in the synapse) by TAAR1 activation and modulation of VMAT2 function, among other mechanisms. The difference in mechanism of action between methylphenidate and dextroamphetamine results in methylphenidate inhibiting dextroamphetamine's effects on monoamine transporters when they are co-administered.

If Vyvanse only works for 8 hours, then perhaps you could ask your pdoc about prescribing you Dexedrine IR (pure dextroamphetamine) to take at the end of the day around late afternoon to early evening, depending on how long your day is. Dexedrine IR takes about 30-60 minutes to get started, and lasts about 4 hours or so per tab, so you could do the math as to when you would need to take it. You'd need some overlap with it as the Vyvanse starts to fizzle out. If try that and feel like the comedown is a little too harsh, you could try the extended release Dexedrine Spansule, which lasts about 6-8 hours, but also takes 30-60 minutes to start working; you could just take it earlier in the day.

If you do the math, Vyvanse 60 mg is about 17.688 mg dextroamphetamine. A step up to 70 mg would be 20.636 mg. If you were to add a tiny 2.5 mg Dexedrine dose (half a 5 mg tab) at the end of the day, that would be pretty close to 70 mg Vyvanse (20.188 mg), although just taking a whole 5 mg tab probably wouldn't be harmful (22.688 mg > 20.188 mg).

If your pdoc doesn't like Dexedrine, then I guess Adderall would have to do... lol. It's not the same. It really isn't. But Vyvanse 60 mg + Adderall 5 mg would be 21.438 mg dextroamphetamine + 1.25 mg levoamphetamine, which would be slightly more noradrenergic and more peripherally-acting.

Anyway, that's what stands out to me. I think if your pdoc stops the Concerta and adds a small Dexedrine dose at the end of the day, or even consolidates you to 20 mg Dexedrine Spansules (10 mg twice a day), then you would be a lot better. If you are having trouble with efficacy at 20 mg, then stepping up to 30 mg might do you some good (15 mg twice daily). But I wouldn't want you to rock the boat if Vyvanse is working for you already. Just adding a small Dexedrine dose might help.

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On 03/09/2018 at 9:24 AM, mikl_pls said:

One theory I have is that you are taking both Vyvanse and Concerta together. Because of their mechanisms of action, they could be fighting each other and canceling each other out.

Interesting. I should have said in my post that this variability was happening before I tacked on Concerta for the afternoons. That said, I can certainly see how something like this would be affecting things. But if it was, wouldn't the canceling-out-ness be consistent?

Quote

While dextroamphetamine (what lisdexamfetamine metabolizes into) and methylphenidate are predominantly dopaminergic drugs, their mechanisms of action are distinct. Methylphenidate acts as a norepinephrine-dopamine reuptake inhibiter (NDRI), while dextroamphetamine acts both as a norepinephrine-dopamine releasing agent (NDRA) and reuptake inhibitor (NDRI). Methylphenidate's mechanism of action in the release of dopamine and norepinephrine is different as it is thought to increase neuronal firing rate, whereas dextroamphetamine reduces firing rate, but causes monoamine release by reversing the flow of the monoamines by causing the monoamine transporters to act in reverse (instead of taking neurotransmitters out of the synapse, they bring them back in the synapse) by TAAR1 activation and modulation of VMAT2 function, among other mechanisms. The difference in mechanism of action between methylphenidate and dextroamphetamine results in methylphenidate inhibiting dextroamphetamine's effects on monoamine transporters when they are co-administered.

I'm a pharmacological layman :) Does this paragraph essentially mean that the Ritalin stomps the build-up of Vyvanse? On the topic of steady state and all that, I always find with stims that the duration I've taken them for does not affect their effectiveness - apart from when they poop out. Every day goes like this, irrespective of the number of days since starting them:

5a : wake up and dose Vyvanse. Feel quite crap until 630a give or take 30 mins (again, that variability)

630a -> 130p : feel 4/10 to 7/10 good, which is a huge variation.

130p : start feeling depressed. Dose Concerta. Feel quite crap until ~ 2:30p

230p -> 830p : again, feel 4/10 to 7/10 good

830p : start feeling depressed. Drink booze to feel better or just go to bed.

I.e. there's no build-up over the days for me seemingly.

Quote

If Vyvanse only works for 8 hours, then perhaps you could ask your pdoc about prescribing you Dexedrine IR (pure dextroamphetamine) to take at the end of the day around late afternoon to early evening, depending on how long your day is. Dexedrine IR takes about 30-60 minutes to get started, and lasts about 4 hours or so per tab, so you could do the math as to when you would need to take it. You'd need some overlap with it as the Vyvanse starts to fizzle out. If try that and feel like the comedown is a little too harsh, you could try the extended release Dexedrine Spansule, which lasts about 6-8 hours, but also takes 30-60 minutes to start working; you could just take it earlier in the day.

I'd come to a (much less authoritative and detailed) similar conclusion. Thanks for verifying it. 

Quote

If you do the math, Vyvanse 60 mg is about 17.688 mg dextroamphetamine. A step up to 70 mg would be 20.636 mg. If you were to add a tiny 2.5 mg Dexedrine dose (half a 5 mg tab) at the end of the day, that would be pretty close to 70 mg Vyvanse (20.188 mg), although just taking a whole 5 mg tab probably wouldn't be harmful (22.688 mg > 20.188 mg).

Nice. Thanks again for the ideas.

Quote

If your pdoc doesn't like Dexedrine, then I guess Adderall would have to do... lol. It's not the same. It really isn't. But Vyvanse 60 mg + Adderall 5 mg would be 21.438 mg dextroamphetamine + 1.25 mg levoamphetamine, which would be slightly more noradrenergic and more peripherally-acting.

Can you expound on Adderall v.s. Dexedrine a bit? Which do you prefer? And what does peripherally-acting mean in this context?

Quote

Anyway, that's what stands out to me. I think if your pdoc stops the Concerta and adds a small Dexedrine dose at the end of the day, or even consolidates you to 20 mg Dexedrine Spansules (10 mg twice a day), then you would be a lot better. If you are having trouble with efficacy at 20 mg, then stepping up to 30 mg might do you some good (15 mg twice daily). But I wouldn't want you to rock the boat if Vyvanse is working for you already. Just adding a small Dexedrine dose might help.

Much, much obliged once again @mikl_pls. You're a champion of the interwebs!

I should say BTW that the reason I posted about this seemingly-minor issue is because every time the Vyvanse is late to kick-in or only gives me a small boost, I freak out thinking that this is it pooping out. And I freak out because every other med I've responded to poops out =/ 

Edited by sming

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On 9/4/2018 at 3:39 PM, sming said:

Interesting. I should have said in my post that this variability was happening before I tacked on Concerta for the afternoons. That said, I can certainly see how something like this would be affecting things. But if it was, wouldn't the canceling-out-ness be consistent?

Oh! I see. Well, the only other thing I could see is that it would have something to do with your digestion, since Vyvanse is activated by digestion. I don't have any theories as to what could have caused the original varied efficacy though, unfortunately, since I'm not too up on lisdexamfetamine's mechanism of action regarding its cleaving of L-lysine from the dextroamphetamine. Any ideas, @browri, @notloki, anyone else who might be familiar with this who I'm not calling upon?

On 9/4/2018 at 3:39 PM, sming said:

I'm a pharmacological layman :) Does this paragraph essentially mean that the Ritalin stomps the build-up of Vyvanse? On the topic of steady state and all that, I always find with stims that the duration I've taken them for does not affect their effectiveness - apart from when they poop out. Every day goes like this, irrespective of the number of days since starting them:

5a : wake up and dose Vyvanse. Feel quite crap until 630a give or take 30 mins (again, that variability)

630a -> 130p : feel 4/10 to 7/10 good, which is a huge variation.

130p : start feeling depressed. Dose Concerta. Feel quite crap until ~ 2:30p

230p -> 830p : again, feel 4/10 to 7/10 good

830p : start feeling depressed. Drink booze to feel better or just go to bed.

I.e. there's no build-up over the days for me seemingly.

My apologies! I didn't mean to bombard you with all that. Yes you pretty much got it. Basically the Concerta/Ritalin essentially fights with Vyvanse/dextroamphetamine because of their mechanisms of action. The Concerta is trying to speed everything up to cause more norepinephrine and dopamine to be in the synapse, where as the Vyvanse is trying to slow everything down and even make things work in reverse to cause release of norepinephrine and dopamine into the synapse. Nothing wins out--Concerta cancels out the Vyvanse, and the Vyvanse cancels out the Concerta. (I guess theoretically if you dosed up one with the other being a lower dose, one might win out, but I don't know for sure.)

Yep, it generally takes about 2 hours or so for Vyvanse to start working since it is activated by digestion, so that span of time between when you take it and when it starts working seems right.

That is a huge variation though in how it affects your mood. It is often said that amphetamines aren't the most effective for depression, but I'm right there with you--I'm taking Dexedrine for treatment-resistant depression among, among other reasons (ADHD-PI, hypersomnolence, weight loss). It is by far the most effective thing I think for my depression. I would guess that inconstancy in efficacy would probably be a reason for considering amphetamines not the best medicine for depression. They used to prescribe them for depression back in the 50's or 60's for depression somewhat regularly, but that was before they had as many antidepressants as we do today. (The picture below is an old advertisement for Dexedrine Spansule for depression...)

rx-dexedrine-ad-antidepressant_640w.jpg

So before you started Concerta, would you just feel like crap for the rest of the day from 2:30 PM onward? Have you considered trying just Concerta? Methylphenidate I believe has a little more benefit for depression. Amphetamines are more potent than methlylphenidate, but there are people who respond to methylphenidate better. There is also, like I said, just plain old Dexedrine and Dexedrine Spansule (the extended release), which really might work better since it's not activated by digestion.

On 9/4/2018 at 3:39 PM, sming said:

Can you expound on Adderall v.s. Dexedrine a bit? Which do you prefer? And what does peripherally-acting mean in this context?

Well, Dexedrine is just pure dextroamphetamine sulfate, but Adderall is a combination of four amphetamine salts (I'll get to that in a sec) yielding a mixture of half "amphetamine" or "racemic amphetamine" (dextroamphetamine + levoamphetamine) + half "dextroamphetamine." This yields a ratio of 75% dextroamphetamine, 25% levoamphetamine. 

The nitty-gritty details of Adderall, if you want to see them, are as follows. You can skip over it if you wish.

Adderall, also called "mixed amphetamine salts," or sometimes just "amphetamine/dextroamphetamine," as aforementioned, is a combination of four amphetamine salts, which are as follows:

  • 25% d-amphetamine sulfate (100% d-amphetamine, 0% l-amphetamine)
  • 25% amphetamine sulfate (50% d-amphetamine, 50% l-amphetamine)
  • 25% d-amphetamine saccharate (100% d-amphetamine, 0% l-amphetamine)
  • 25% amphetamine aspartate monohydrate (50% d-amphetamine, 50% l-amphetamine)

So this is 50% total amphetamine (50% d-amphetamine, 50% l-amphetamine), 50% d-amphetamine (100% d-amphetamine, 0% l-amphetamine). This is a ratio of 75% d-amphetamine, 25% l-amphetamine.

Anyway... So this is what all this means.

Overall, between dextroamphetamine and amphetamine, the primary neurotransmitter they release is norepinephrine, the secondary neurotransmitter they release is dopamine, and the tertiary neurotransmitter they release is serotonin; however, compared to racemic amphetamine (aka just "amphetamine," also marketed as "Evekeo," but which is present in Adderall in a 50/50 ratio as aforementioned, yielding the 75/25 or 3:1 ratio of d-:l-amphetamine), Dexedrine (pure d-amphetamine, what Vyvanse turns into...) is more dopaminergic and less "peripherally-acting" than Adderall (and Evekeo for that matter...).

"Peripherally-acting" means that Adderall (and Evekeo) will work more on the peripheral nervous system (as opposed to the central nervous system) than Dexedrine (Dexedrine is a very potent central nervous system stimulant; Adderall and Evekeo are too, just not quite as much as Dexedrine is... and Vyvanse for that matter). That means more sweating, tremor, fast heart rate, etc. This is due to more noradrenergic activity from the presence of racemic amphetamine. Dexedrine can cause all this too, but for some people, not really to the extent that Adderall does.

If you're looking for a TL;DR...

Adderall is 75% d-amphetamine, 25% l-amphetamine.

Dexedrine is 100% d-amphetamine. (So is Vyvanse).

 

As far as how it affects me?

I personally like Dexedrine better because to me it feels more potent, not quite as "jittery," I feel more alert, I can concentrate 100x more, my depression is tons better on it, and honestly, I could go on and on about it. I'm on the max dose, 60 mg, of it. I still feel like I could use a little more. I have honestly experimented with the dose, and I feel like I could occasionally use 90 mg, but not every day... 60 mg is where I belong I think every day. I take 40 mg on days I feel I don't need quite as much, but I don't not take it (i.e., drug holidays). Otherwise my mood would plummet to hell. I find that this 40-60 mg dosing strategy keeps it working the way it should. I wish I could get enough to take more because I find myself dragging some days with my hypersomnolence, but until I go back to a real sleep doctor, that probability is probably nil. 

I find that Adderall 60 mg (max dose) is probably about as effective as Dexedrine 40 mg. Mathematically (and theoretically) it should be "equivalent" to about 45 mg, which is different to the clinical picture, but these mathematical "equivalencies" really probably shouldn't be relied upon.

Obviously, I vastly prefer Dexedrine. ;)

On 9/4/2018 at 3:39 PM, sming said:

Much, much obliged once again @mikl_pls. You're a champion of the interwebs!

I should say BTW that the reason I posted about this seemingly-minor issue is because every time the Vyvanse is late to kick-in or only gives me a small boost, I freak out thinking that this is it pooping out. And I freak out because every other med I've responded to poops out =/ 

Aww thanks man :)

I hear ya! I freak out about my cocktail pooping out because I just recently found one that semi-decently works, and I'm like "NO! THIS MUST NOT HAPPEN!"

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What are you eating and drinking before you take the Vyvanse ? Things acidic will interfere with amphetamine so no OJ or Coke or other soft drinks. No grapefruit juice !!  For me my morning routine is eat a bit of cheese to buffer all the pills (12) I take in the morning. Take pills with water. NO food and only water for an hour after taking pills. 

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5 hours ago, notloki said:

What are you eating and drinking before you take the Vyvanse ? Things acidic will interfere with amphetamine so no OJ or Coke or other soft drinks. No grapefruit juice !!  For me my morning routine is eat a bit of cheese to buffer all the pills (12) I take in the morning. Take pills with water. NO food and only water for an hour after taking pills. 

I thought the acidity problem was with the Dexedrine Spansules because of the release mechanism (among a few others stims)? Wasn't the point of making lisdexamfetamine to overcome this by causing the whole reaction to occur hemolytically (other than the abuse deterrence)? Vyvanse isn't really formulated as an extended release. I thought it's ER mechanism was due to the way that lysine is cleaved from dextroamphetamine over time in the blood stream. As far as I know, the one way to modify the metabolism of Vyvanse is trypsin inhibitors like soybeans or proteolytic enzyme supplements which contain supplemental trypsin which would do the opposite because trypsin is responsible for the cleavage of lysine from dextroamphetamine.

@mikl_pls does any of this sound familiar, or am I totally off the rails?

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No, it is amphetamine that is affected by an acidic environment. 

"Acidic substances reduce the absorption of amphetamine and increase urinary excretion, and alkaline substances do the opposite."

https://en.wikipedia.org/wiki/Amphetamine

 

Edited by notloki
proof

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3 hours ago, browri said:

I thought the acidity problem was with the Dexedrine Spansules because of the release mechanism (among a few others stims)? Wasn't the point of making lisdexamfetamine to overcome this by causing the whole reaction to occur hemolytically (other than the abuse deterrence)? Vyvanse isn't really formulated as an extended release. I thought it's ER mechanism was due to the way that lysine is cleaved from dextroamphetamine over time in the blood stream. As far as I know, the one way to modify the metabolism of Vyvanse is trypsin inhibitors like soybeans or proteolytic enzyme supplements which contain supplemental trypsin which would do the opposite because trypsin is responsible for the cleavage of lysine from dextroamphetamine.

@mikl_pls does any of this sound familiar, or am I totally off the rails?

This is all news to me.

I'm not sure whether the dextroamphetamine, once cleaved from the lysine, would be at a point where it could be affected by acidity or not. I'll have to look all this up. I haven't researched lisdexamfetamine very much.

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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873712/

Quote

In an in vitro study, the pH solubility profile of LDX was determined in buffered aqueous solutions using an assay specific for LDX. The environmental pH did not affect the solubility profile of LDX within the biological pH range (pH, 1-8), suggesting that gastric pH variation does not affect the absorption of LDX.

Haffey et al. compared the pharmacokinetics of LDX and MAS-XR, alone or with omeprazole (Prilosec, AstraZeneca), a proton pump inhibitor that has been shown to decrease basal gastric acid output by as much as 94%. In 24 adults 18 to 45 years of age, total exposure was unaffected by omeprazole for both LDX and MAS-XR. However, for MAS-XR, which uses a pH-sensitive beaded technology, the median Tmax was decreased by 2.25 hours when MAS-XR and omeprazole were co-administered (Tmax = 2.75 hours), compared with MAS-XR administered alone (Tmax = 5 hours). No median Tmax difference was found with coadministration of LDX and omeprazole. This suggests that there is no drug interaction with medications that lower GI pH with the prodrug LDX.

Non clinical in vivo and in vitro studies designed to investigate the absorption and hydrolysis of LDX using rodent and human tissues suggest that absorption of LDX occurs primarily in the small intestine and that conversion of LDX into active d-amphetamine occurs primarily in the blood. In the rodent, intact LDX was readily absorbed through duodenal, jejunal, and ileal intestinal segments and underwent pre-systemic enzymatic conversion to active d-amphetamine. In the presence of rat and human whole blood, LDX was converted to amphetamine. However, conversion did not occur in plasma or human white blood cells or platelets. Studies of in vitro enzymatic conversion by human blood cell fractions demonstrated that LDX was converted into active d-amphetamine by red blood cells.

From this, I get that lisdexamfetamine is not affected by gastric pH, and that the conversion of it into active dextroamphetamine occurs primarily in the lower parts of the intestines and the blood.

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@notloki

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823324/

Quote

 

Factors that influence a drug’s rate of transit through, and uptake from, the GI tract include the presence of food and pH [20–22]. In a single-dose crossover study, Krishnan and Zhang [23] reported that d-amphetamine Tmax was delayed by approximately 1 h in healthy adults (N = 18) administered LDX 70 mg following a high-fat meal compared with those who fasted; there were no significant differences in Cmax, AUC0–∞ or t½ (Table 2; high-fat meal defined in legend). In contrast, while Tmax for intact LDX also exhibited a significant delay of approximately 1 h, Cmax was significantly lower and t½ significantly longer in the fed than in the fasted state, although AUC0–∞ was unaffected (N = 8) (Table 3) [24]. Following orally administered extended-release mixed amphetamine salts (MAS XR), however, the mean Tmax of plasma d-amphetamine was reported as approximately 2.5 h longer in fed than in fasted individuals, with Cmax and AUC0–∞ modestly lower [21, 22]. These results suggest that LDX hydrolysis, rather than GI transit and uptake, is the dominant factor in determining the d-amphetamine exposure profile following oral administration of LDX.

GI disorders, including ulcers and dyspepsia, are commonly treated using proton pump inhibitors, such as omeprazole, to suppress acid secretion by the stomach mucosa and thereby increase the pH. The inhibition of gastric acid secretion may, however, interfere with the absorption of drugs for which pH is an important determinant of bioavailability [25], such as MAS XR which uses pH-sensitive beaded technology to achieve phased release. Haffey et al. [26] reported that the median Tmax for total amphetamine was approximately 2 h shorter in healthy adults when MAS XR was co-administered with omeprazole (Tmax, 2.75 h) than when administered alone (Tmax, 5 h) (N = 24). In the same study, d-amphetamine pharmacokinetic parameters remained largely unaltered when LDX was co-administered with oral omeprazole (Table 2). Thus, these results indicate that, unlike MAS XR, LDX provided an amphetamine exposure profile that was unaffected by administration of a proton pump inhibitor.

LDX is soluble in water [9] and can, therefore, be administered as a solution or mixed into food to individuals who experience difficulty in swallowing capsules, or in circumstances when the monitoring of drug consumption is a requirement. This differs from other long-acting stimulant formulations which rely on mechanical phased release of the active drug from a capsule. In another study (NCT01890785), similar values of d-amphetamine Cmax and AUC0–96h were seen when oral LDX 70 mg was administered to healthy adults as capsules, or capsule contents were dissolved in orange juice or mixed into vanilla yogurt [27]; in addition administration with yogurt delayed Tmax by only 0.4 h compared with the fasted state [9].

To summarise, the above LDX single-dose studies suggest that the hydrolysis of LDX to d-amphetamine in the blood is the rate-limiting step, rather than the uptake of the parent drug from the GI tract. This leads to consistent intra- and inter-individual d-amphetamine exposure profiles.

 

So while food does affect the pharmacokinetics of lisdexamfetamine, acidity doesn't make an appreciable difference in contrast to the effect pH has on unbonded amphetamine salts.

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Have you and pdoc eve talked about the adderall/Dexedrine ER versions? Might be 2 birds 1 stone if you could eliminate the Concerta 

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If it is in the lower intestine there will not be much effect on amphetamine. But if the amphetamine is in the stomach an acidic environment will slow absorption. I take 2 tums with my Adderall to avoid this and it makes a considerable difference.  I also have GERD to consider. 

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... total exposure was unaffected by omeprazole 

I take omeprazole and was going to ask about this. Now I don't - nice one!

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On 06/09/2018 at 11:53 PM, mikl_pls said:

Oh! I see. Well, the only other thing I could see is that it would have something to do with your digestion, since Vyvanse is activated by digestion. I don't have any theories as to what could have caused the original varied efficacy though, unfortunately, since I'm not too up on lisdexamfetamine's mechanism of action regarding its cleaving of L-lysine from the dextroamphetamine. Any ideas, @browri, @notloki, anyone else who might be familiar with this who I'm not calling upon?

My apologies! I didn't mean to bombard you with all that. Yes you pretty much got it. Basically the Concerta/Ritalin essentially fights with Vyvanse/dextroamphetamine because of their mechanisms of action. The Concerta is trying to speed everything up to cause more norepinephrine and dopamine to be in the synapse, where as the Vyvanse is trying to slow everything down and even make things work in reverse to cause release of norepinephrine and dopamine into the synapse. Nothing wins out--Concerta cancels out the Vyvanse, and the Vyvanse cancels out the Concerta. (I guess theoretically if you dosed up one with the other being a lower dose, one might win out, but I don't know for sure.)

Yep, it generally takes about 2 hours or so for Vyvanse to start working since it is activated by digestion, so that span of time between when you take it and when it starts working seems right.

That is a huge variation though in how it affects your mood. It is often said that amphetamines aren't the most effective for depression, but I'm right there with you--I'm taking Dexedrine for treatment-resistant depression among, among other reasons (ADHD-PI, hypersomnolence, weight loss). It is by far the most effective thing I think for my depression. I would guess that inconstancy in efficacy would probably be a reason for considering amphetamines not the best medicine for depression. They used to prescribe them for depression back in the 50's or 60's for depression somewhat regularly, but that was before they had as many antidepressants as we do today. (The picture below is an old advertisement for Dexedrine Spansule for depression...)

rx-dexedrine-ad-antidepressant_640w.jpg

So before you started Concerta, would you just feel like crap for the rest of the day from 2:30 PM onward? Have you considered trying just Concerta? Methylphenidate I believe has a little more benefit for depression. Amphetamines are more potent than methlylphenidate, but there are people who respond to methylphenidate better. There is also, like I said, just plain old Dexedrine and Dexedrine Spansule (the extended release), which really might work better since it's not activated by digestion.

Well, Dexedrine is just pure dextroamphetamine sulfate, but Adderall is a combination of four amphetamine salts (I'll get to that in a sec) yielding a mixture of half "amphetamine" or "racemic amphetamine" (dextroamphetamine + levoamphetamine) + half "dextroamphetamine." This yields a ratio of 75% dextroamphetamine, 25% levoamphetamine. 

The nitty-gritty details of Adderall, if you want to see them, are as follows. You can skip over it if you wish.

Adderall, also called "mixed amphetamine salts," or sometimes just "amphetamine/dextroamphetamine," as aforementioned, is a combination of four amphetamine salts, which are as follows:

  • 25% d-amphetamine sulfate (100% d-amphetamine, 0% l-amphetamine)
  • 25% amphetamine sulfate (50% d-amphetamine, 50% l-amphetamine)
  • 25% d-amphetamine saccharate (100% d-amphetamine, 0% l-amphetamine)
  • 25% amphetamine aspartate monohydrate (50% d-amphetamine, 50% l-amphetamine)

So this is 50% total amphetamine (50% d-amphetamine, 50% l-amphetamine), 50% d-amphetamine (100% d-amphetamine, 0% l-amphetamine). This is a ratio of 75% d-amphetamine, 25% l-amphetamine.

Anyway... So this is what all this means.

Overall, between dextroamphetamine and amphetamine, the primary neurotransmitter they release is norepinephrine, the secondary neurotransmitter they release is dopamine, and the tertiary neurotransmitter they release is serotonin; however, compared to racemic amphetamine (aka just "amphetamine," also marketed as "Evekeo," but which is present in Adderall in a 50/50 ratio as aforementioned, yielding the 75/25 or 3:1 ratio of d-:l-amphetamine), Dexedrine (pure d-amphetamine, what Vyvanse turns into...) is more dopaminergic and less "peripherally-acting" than Adderall (and Evekeo for that matter...).

"Peripherally-acting" means that Adderall (and Evekeo) will work more on the peripheral nervous system (as opposed to the central nervous system) than Dexedrine (Dexedrine is a very potent central nervous system stimulant; Adderall and Evekeo are too, just not quite as much as Dexedrine is... and Vyvanse for that matter). That means more sweating, tremor, fast heart rate, etc. This is due to more noradrenergic activity from the presence of racemic amphetamine. Dexedrine can cause all this too, but for some people, not really to the extent that Adderall does.

If you're looking for a TL;DR...

Adderall is 75% d-amphetamine, 25% l-amphetamine.

Dexedrine is 100% d-amphetamine. (So is Vyvanse).

roger that. Thanks. That's what I'd surmised but I wasn't confident in my surmisation. Not that that's a word but there you go. 
Also, apologies for the extremely slow responses. I have some weird OCD about replying to stuff. Just ask my friends & family.

On 06/09/2018 at 11:53 PM, mikl_pls said:

As far as how it affects me?

I personally like Dexedrine better because to me it feels more potent, not quite as "jittery," I feel more alert, I can concentrate 100x more, my depression is tons better on it, and honestly, I could go on and on about it.

This is music to my ears. I've floated Dexedrine to my inexpensive, ignorant-but-sometimes-progressive PDoc to no response. I'll keep at it.

On 06/09/2018 at 11:53 PM, mikl_pls said:

I'm on the max dose, 60 mg, of it. I still feel like I could use a little more. I have honestly experimented with the dose, and I feel like I could occasionally use 90 mg, but not every day... 60 mg is where I belong I think every day. I take 40 mg on days I feel I don't need quite as much, but I don't not take it (i.e., drug holidays).

I'm the same with 60mg Vyvanse. It helps immeasurably but I still feel somewhat empty/anhedonic - just not "right". I've tried not taking it and it was a short, sharp, horrific return to my normal state of wellbeing. I.e. I wanted to be dead very quickly and very intensely.

On 06/09/2018 at 11:53 PM, mikl_pls said:

Otherwise my mood would plummet to hell. I find that this 40-60 mg dosing strategy keeps it working the way it should. I wish I could get enough to take more because I find myself dragging some days with my hypersomnolence, but until I go back to a real sleep doctor, that probability is probably nil. 

I hear ya. And getting insurance to pay for anything hypersomnolence-related is like finding rocking horse sh*t. 

On 06/09/2018 at 11:53 PM, mikl_pls said:

I find that Adderall 60 mg (max dose) is probably about as effective as Dexedrine 40 mg. Mathematically (and theoretically) it should be "equivalent" to about 45 mg, which is different to the clinical picture, but these mathematical "equivalencies" really probably shouldn't be relied upon.

Obviously, I vastly prefer Dexedrine. ;)

Aww thanks man :)

I hear ya! I freak out about my cocktail pooping out because I just recently found one that semi-decently works, and I'm like "NO! THIS MUST NOT HAPPEN!"

Yep, today was another day where I worry since Vyvanse lasted at best 3 hours. Very, very concerning. But so far I've "bounced back" twice so here's hoping. Thanks again man,

Pete

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On 07/09/2018 at 10:56 AM, notloki said:

What are you eating and drinking before you take the Vyvanse ? Things acidic will interfere with amphetamine so no OJ or Coke or other soft drinks. No grapefruit juice !!  For me my morning routine is eat a bit of cheese to buffer all the pills (12) I take in the morning. Take pills with water. NO food and only water for an hour after taking pills. 

Hi & thanks for the idea. I take nothing with Vyvanse, except my other meds (apart from the antacids). I find it works best for me if I don't eat anything for a good hour+ after dosing. I learned about the acid/alkali thing last week. I'm already on the FODMAP diet and have IBS-C so a lot of those things I haven't had for 10 years anyway. 

I ordered Inositol, Magnesium Taurate and Magnesium Glycinate  since numerous places recommend them to A) reduce side-effects (N/A for me, really) and B) raise blood-levels of the med. I'm trying one at a time in some vain hope of being scientific.

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Quote

In contrast, while Tmax for intact LDX also exhibited a significant delay of approximately 1 h, Cmax was significantly lower and t½ significantly longer in the fed than in the fasted state, although AUC0–∞ was unaffected 

from this I take "don't eat for a good 90 mins" after dosing Vyvanse. Is that about right? That may explain my malaise today since I ate a high-protein brekkie (whole wheat toast, lots of butter & peanut butter + glass of milk) just after dosing.

On 08/09/2018 at 4:16 PM, Iceberg said:

Have you and pdoc eve talked about the adderall/Dexedrine ER versions? Might be 2 birds 1 stone if you could eliminate the Concerta 

I'm working on it. He's a steady-Eddie dinosaur type who you have to steer carefully. No sharp turns or you'll just get blanket "No"'s. My insurance just isn't playing ball at the moment so I'll have to goodrx whatever I get anyway. The main hurdle is actually the FDA (?) well, government. I'm not allowed my prescribed amount of Concerta because it's too much in their twisted calculations. Sigh.

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On 08/09/2018 at 7:50 PM, notloki said:

If it is in the lower intestine there will not be much effect on amphetamine. But if the amphetamine is in the stomach an acidic environment will slow absorption. I take 2 tums with my Adderall to avoid this and it makes a considerable difference.  I also have GERD to consider. 

Interesting. I take a PPI for NERD (GERD's non-erosive sibling). It does the job but I sometimes also take 150mg ranitidine if I'm still feeling the reflux. I wonder if that's a factor...

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8 hours ago, sming said:

Yep, today was another day where I worry since Vyvanse lasted at best 3 hours.

Yeah... Vyvanse, for me, lasted, at best, like 4 hours, man... I hated that medicine. Dexedrine Spansule is the way to go, but if your pdoc is all "ooh Dexedrine is bad! You'll abuse it!" Just tell him that Adderall is just re-branded Obetrol, and Andy Warhol used to abuse the entire shit out of that stuff...

See... originally, back in the 50's and 60's, Obetrol was a brand of mixed amphetamine salts that included methamphetamine indicated for weight loss approved by the FDA. It was offered in two strengths, 10 mg and 20 mg, through Obetrol Pharmaceuticals division of an American pharmaceutical company "Rexar" under the trade name "Obetrol." By the 1990s, Obetrol Pharmaceuticals had been wholly absorbed by Rexar Pharmacal and was no longer noted as a "division" of Rexar. In 1993, Rexar was acquired by Richwood Pharmaceuticals, which in 1995 merged with Shire Pharmaceuticals.

Per the 1972 Physicians' Desk Reference, Obetrol contained (per 10 mg tablet):

  • 2.5 mg methamphetamine saccharate
  • 2.5 mg methamphetamine hydrochloride
  • 2.5 mg racemic amphetamine sulfate
  • 2.5 mg dextroamphetamine sulfate

Rexar reformulated Obetrol to exclude methamphetamine and continued to sell this new formulation under the same Obetrol brand name. This new unapproved formulation was later rebranded and sold as Adderall by Richwood after it acquired Rexar resulting in FDA warning in 1994. Richwood submitted this formulation as NDA 11-522 and Adderall gained FDA approval for the treatment of ADHD therapy on February 13, 1996.

By 1995, the year Shire Pharmaceuticals (then known as Shire-Richwood) acquired Rexar Pharmacal, Obetrol 10 mg, and 20 mg, tablets contained, (in equal proportions):

  • Dextroamphetamine sulfate
  • Dextroamphetamine saccharine
  • Amphetamine sulfate
  • Amphetamine aspartate

So if your pdoc wants to make a case about abuse of dextroamphetamine (Dexedrine), as though Dexedrine is more abusable than Adderall or whatever, then there's a little history of Adderall to back that up. Also, all forms of amphetamines were abused and over-prescribed back in the 50's and 60's, not just dextroamphetamine... there was methamphetamine, racemic amphetamine, phenmetrazine, etc.

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Lol technically speaking I think you can still get methamphetamine in severe cases of ADHD and obesity

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41 minutes ago, browri said:

Lol technically speaking I think you can still get methamphetamine in severe cases of ADHD and obesity

I have taken methamphetamine (brand name Desoxyn) twice. I'm not really a fan of it, tbh.

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2 hours ago, mikl_pls said:

I have taken methamphetamine (brand name Desoxyn) twice. I'm not really a fan of it, tbh.

Haha really? Dexedrine is better? 

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7 hours ago, Iceberg said:

Haha really? Dexedrine is better? 

IIRC methamphetamine is metabolized into amphetamine. Quite a bit of methamphetamine is excreted by the kidneys, unchanged, where pH affects rate of excretion. Methamphetamine lasts a long time as it is slowly metabolized into amphetamine. I would suspect methamphetamine is active itself. 

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14 hours ago, Iceberg said:

Haha really? Dexedrine is better? 

To me, yes. The second time around on Desoxyn, I remember feeling very tearful, mopey, and generally dysphoric. Now, it could've been that my dose (15 mg Desoxyn) wasn't comparable to the Dexedrine 30 mg I had been on prior to switching to the Desoxyn... I actually never made it to a "therapeutic" dose of Desoxyn, which is considered 20-25 mg/day. My pdoc put the cap at 15 mg/day and that was it. No more, she said.

I'm curious as to whether my NP would be willing to prescribe it to me at a therapeutic dose, but I'm also curious as to whether 25 mg Desoxyn would be even remotely as psychostimulatory as 60 mg Dexedrine... Better not rock the boat...

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Hi guys, 

thanks so much for all the input on Vyvanse and its brethren and apologies for not keeping up - I've been in a bad way. Unfortunately this topic is moot now since Vyvanse seems to have completely pooped out on me. Since Saturday, these changes have happened:

  • Emotional balance -> erratic, negative emotions. Anger, depression, aggression, despondency.
  • Generally OK mood -> deep, dark depression. That horrible empty feeling in your gut.
  • Interested in things, hobbies etc. -> deep anhedonia & staring at the wall for hours.
  • Energy and feeling alert -> spontaneously falling asleep.
  • Positive outlook -> can't see anything but doom & suicide.

This is my MO when I find a med/combo that helps it would seem. I get 2-6 weeks of benefit, then an abrupt crash back to the pits of depression. I've tried adding on 10mg or 20mg of Ritalin but that just makes me fall asleep faster and for longer. I may try the magnesium taurate & the Inositol at some point but it looks like the very mechanism of Vyvanse (and Concerta) has flipped on my brain. Increasing via supplements just feels the wrong direction.

Now, I have to admit that I've had very, very bad pain since Saturday (I have chronic back & abdominal pain) however I don't know if that's contributing to the crash or because of it.

Either way I'm seeing my PDoc sooner rather than later if this continues once my pain has let up (hopefully soon) since I'll be out of a job at this rate. Looking through mood spreadsheets, I did quite well on Lexapro (weirdly, for someone with TRD) and Bupropion years back. I might add Lexapro for some stability, take a break from stims and have another go with them.

Thanks again and good luck to all,

Pete

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On 17/09/2018 at 12:33 AM, mikl_pls said:

Yeah... Vyvanse, for me, lasted, at best, like 4 hours, man... I hated that medicine. Dexedrine Spansule is the way to go, but if your pdoc is all "ooh Dexedrine is bad! You'll abuse it!" Just tell him that Adderall is just re-branded Obetrol, and Andy Warhol used to abuse the entire shit out of that stuff...

...

So if your pdoc wants to make a case about abuse of dextroamphetamine (Dexedrine), as though Dexedrine is more abusable than Adderall or whatever, then there's a little history of Adderall to back that up. Also, all forms of amphetamines were abused and over-prescribed back in the 50's and 60's, not just dextroamphetamine... there was methamphetamine, racemic amphetamine, phenmetrazine, etc.

Thanks so much again man! I've been gently pushing for dexedrine without much luck. As per my post just now though, I'm not sure my brain is respecting stims any more, devastatingly. I bumped my Abilify from 5 to 7.5mg yesterday so I just have to pray (to no God - I'm atheist) that does something positive. I might see if I can chuck in Lexapro to get some stability since right now I'm an aggressive, despondent mess :/

Pete

On 18/09/2018 at 2:52 AM, mikl_pls said:

Better not rock the boat...

hah. Amen.

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