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jeva39

Why might someone sensitive to the effects of psych meds have difficulties with word recall at low doses of Vyvanse (currently 20mg)?

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Posted (edited)

I feel as though i can think more clearly than ever, but my vocabulary and concentration is quite limited compared to before. higher doses were even more impairing- felt much more foggy headed. PA remarked that it's likely due to my being so "sensitive". i wonder if 10 mg would be more suitable, but i hesitate to make another dose change because i am otherwise doing very well at the current dose. it seems to me that trade offs that frequently cancel out the benefits of a med are unavoidable..still i wonder if fish oil might assist me in my aims... i also ponder whether my mildly impaired speech is at least partly a psychological/emotional issue stemming from feelings of inadequacy (AvPD diagnosis).. but it's not solely inadequacy that fuels my anxiety around this issue, but also a desire to engage in creative work for personal enrichment.. it's also a simple quality of life issue.
in any case, does anyone know if low doses have more of an effect of norepenephrine as opposed to dopamine at higher doses? if so how would such a finding correlate with my experience at current dose and of being sensitive to the effects of Vyvanse and psych meds generally?

Edited by jeva39

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Have you had that response with other stimulants?

That happens to me sometimes on stimulants but not always.  Sleep, diet, and exercise all seem to effect how I respond to stimulants.  

Vyvanse doesn't become fully active until it's metabolized by your liver.   There are some food and drug interactions as well as other health conditions that can interfere with this.  

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Posted (edited)

I can't really say for sur whether iv had the same response with other stimulants, my memory taking those other meds (ritalin and conceta) are a little hazy. but i have often been very sensitive to meds generally. im not sure but maybe thats a result of treatment resistant depression?

when you say Vyvanse doesn't become fully active until its metabolized by liver, how long does that generally take, if i may ask?

I am trying to exercise and sleep regularly in addition to taking the vyvanse. i intend on starting fish oil tommorow in hopes that it might clear up some of these issues eventually. fyi: i dont have an ADD diagnosis so my response to meds may be different from yours, but i'm not sure... thanks for responding :))

Edited by jeva39

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2 hours ago, jeva39 said:

I can't really say for sur whether iv had the same response with other stimulants, my memory taking those other meds (ritalin and conceta) are a little hazy. but i have often been very sensitive to meds generally. im not sure but maybe thats a result of treatment resistant depression?

when you say Vyvanse doesn't become fully active until its metabolized by liver, how long does that generally take, if i may ask?

I am trying to exercise and sleep regularly in addition to taking the vyvanse. i intend on starting fish oil tommorow in hopes that it might clear up some of these issues eventually. fyi: i dont have an ADD diagnosis so my response to meds may be different from yours, but i'm not sure... thanks for responding :))

good luck with vyvanse. It was the game changer for me. it is the lynch pin in my med cocktail, hope its the same for you

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7 hours ago, jeva39 said:

in any case, does anyone know if low doses have more of an effect of norepenephrine as opposed to dopamine at higher doses? if so how would such a finding correlate with my experience at current dose and of being sensitive to the effects of Vyvanse and psych meds generally?

It could be that the dextroamphetamine being metabolized from the lisdexamfetamine in Vyvanse is a little too potent for you, and perhaps you may respond better to methylphenidate (Ritalin).

Dextroamphetamine is about equipotent as far as dopamine and norepinephrine release goes, maybe a little stronger on dopamine, so dosage isn't going to really affect NE release vs DA release. But what could be happening here is overstimulation of your noradrenergic system, which could cause issues with the "signal to noise ratio" (Stahl explains this a certain way, I can't remember exactly what it was. @browri can likely help me out here...) But not enough noradrenergic stimulation can cause the same problem. It needs to be "tuned in" just right. The last thing you would want to do in this case is go to something like Adderall or especially Evekeo because they're more noradrenergic and more active on the peripheral nervous system than dextroamphetamine, which is more focused to the central nervous system. If you're set on amphetamine-based stimulants, you could probably try Desoxyn, which is prescription methamphetamine. Yes, this is used sometimes... Just almost no one will prescribe it because of the stigma associated with methamphetamine. It is similarly more dopaminergic than noradrenergic, but slightly less potent than dextroamphetamine. One problem with methamphetamine is that even at therapeutic doses, it is neurotoxic to serotonin neurons. 

But I suggest changing to methylphenidate, because, IIRC, it's more dopaminergic than noradrenergic, and it might be just right for your brain's neurotransmitter needs. Also, it causes your neurotransmitters to raise via a different mechanism. Methylphenidate is an NDRI, whereas D-AMP is an NDRA (primarily, secondarily an NDRI too)--D-AMP and other amphetamines kind of "force" the neurotransmitters out of the neurons, where as methylphenidate blocks the transport of the neurotransmitters out of the neuron synapse, sort of allowing it to "marinade" in the synapse longer, similar to how an SSRI works or an SNRI.

I hope that answers your question.

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thanks mikl, going to run by everything you just wrote with my PA if things ultimately dont work out with the vyvanse  :D

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10 hours ago, mikl_pls said:

It could be that the dextroamphetamine being metabolized from the lisdexamfetamine in Vyvanse is a little too potent for you, and perhaps you may respond better to methylphenidate (Ritalin).

Dextroamphetamine is about equipotent as far as dopamine and norepinephrine release goes, maybe a little stronger on dopamine, so dosage isn't going to really affect NE release vs DA release.

As far as I know amphetamine as a whole molecule is definitely equipotent for norepinephrine and dopamine. However, when it's broken into its two mirror halves (levoamphetamine [L-AMP] and dextroamphetamine [D-AMP]), L-AMP is preferential to norepinephrine and as such increases vigilance, alertness, and cardiac activity, whereas D-AMP is preferential to D-AMP and as such increases task completion reward (i.e. positive chemical reinforcement for completing a task).

Norepinephrine and dopamine are both catecholamines. So increasing one will to a certain degree inadvertently increase the other due to inter-conversion in the brain. D-AMP will cause some direct norepinephrine activation but not as much as L-AMP or the combined amphetamine molecule.

Because of these differences, some people say that Adderall (which is a mixture of amphetamine [containing both L-AMP and D-AMP] as well as some straight D-AMP) makes them feel like they've had too much coffee, whereas all D-AMP like in Dexedrine (dextroamphetamine) and Vyvanse (lisdexamfetamine) can give you the task reward effects without excessive stimulation of the adrenergic system. However, some people need that stimulation, and for that reason, D-AMP solo may not be an option.

10 hours ago, mikl_pls said:

But what could be happening here is overstimulation of your noradrenergic system, which could cause issues with the "signal to noise ratio" (Stahl explains this a certain way, I can't remember exactly what it was. @browri can likely help me out here...) But not enough noradrenergic stimulation can cause the same problem. It needs to be "tuned in" just right. The last thing you would want to do in this case is go to something like Adderall or especially Evekeo because they're more noradrenergic and more active on the peripheral nervous system than dextroamphetamine, which is more focused to the central nervous system. If you're set on amphetamine-based stimulants, you could probably try Desoxyn, which is prescription methamphetamine. Yes, this is used sometimes... Just almost no one will prescribe it because of the stigma associated with methamphetamine. It is similarly more dopaminergic than noradrenergic, but slightly less potent than dextroamphetamine. One problem with methamphetamine is that even at therapeutic doses, it is neurotoxic to serotonin neurons. 

For ADHD, Stahl and many others postulate that norepinephrine and dopamine signaling in the pre-frontal cortex of the brain (PFC) plays the most important role in ADHD symptoms and overall executive functioning. It is believed to operate on a bell curve, if you don't mind me giving a math lesson :P

Image result for bell curve

Imagine that the X-axis (bottom) is the level of norepinephrine/dopamine (NE/DA) stimulation in the PFC and the Y-axis (left-side, top to bottom) is the treatment effect. What this suggests is that a level of noradrenergic and dopaminergic stimulation somewhere in the middle is the most optimal effect. Said another way, there is both a "too high" and a "too low". Someone being treated for ADHD starts at the bottom of their stimulant dose range and slowly increases until they achieve optimal effect while maintaining tolerability. However, it's possible to "over-shoot" it and increase past the level of NE/DA stimulation that is appropriate for your PFC. Using Vyvanse for an example, a patient may find that they don't get any optimal effect from 10, 20, or 30mg of Vyvanse, they may see the most improvement at 40mg and 50mg, and then starting at 60mg things start to "fall apart" and by 70mg, your executive functioning has already deteriorated to a level more similar to when you weren't taking Vyvanse or when you were just taking 10-20mg.

10 hours ago, mikl_pls said:

But I suggest changing to methylphenidate, because, IIRC, it's more dopaminergic than noradrenergic, and it might be just right for your brain's neurotransmitter needs. Also, it causes your neurotransmitters to raise via a different mechanism. Methylphenidate is an NDRI, whereas D-AMP is an NDRA (primarily, secondarily an NDRI too)--D-AMP and other amphetamines kind of "force" the neurotransmitters out of the neurons, where as methylphenidate blocks the transport of the neurotransmitters out of the neuron synapse, sort of allowing it to "marinade" in the synapse longer, similar to how an SSRI works or an SNRI.

I hope that answers your question.

So all stimulants are both NDRAs (norepinephrine/dopamine releasing agents) as well as NDRIs (norepinephrine/dopamine reuptake inhibitors). However some lean more one way or the other. The methylphenidate-based stimulants do have some releasing agent properties but are more potently reuptake inhibitors. Whereas amphetamine-based stimulants are generally more potent releasing agents.

Active and Passive are two words that I like to use here. A releasing agent, ACTIVELY increases the levels of NE and DA in the synapse by causing neurons to expel their contents into the synapse. This is something that your brain already does, it releases neurotransmitters from one neuron into the synapse, which are accepted by another neuron, then the other neuron releases the neurotransmitters back into the synapse, where the process of reuptake causes the neurotransmitters to be re-absorbed by the sending neuron/cell. Reuptake inhibitors are Passive agents in that instead of actively causing NE/DA to be expelled from neurons, they inhibit reuptake and prevent neurotransmitters from returning from the synapse to the neuron....they PASSIVELY increase neurotransmitters by PREVENTING the brain from "cleaning up after itself", said a certain way.

For this very reason, some consider methylphenidate-based stimulants to be more "mild" in effect and potentially more tolerable. It's also why they are the stimulants of choice in children before moving on to the amphetamine-based options like Adderall or Vyvanse.

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does anyone know if lower doses of stimulants have more of an effect on NE as opposed to DA at higher doses? also if i may ask, what is the difference (put in layman's terms) d-methylphenidate vs d-l methylphenidate and why would one be more beneficial than the other?

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48 minutes ago, jeva39 said:

does anyone know if lower doses of stimulants have more of an effect on NE as opposed to DA at higher doses? also if i may ask, what is the difference (put in layman's terms) d-methylphenidate vs d-l methylphenidate and why would one be more beneficial than the other?

Adderall is a combo of different amphetamine salts:

25% amphetamine aspartate monohydrate (12.5% levo, 12.5% dextro)
25% amphetamine sulfate (12.5% levo, 12.5% dextro)
25% dextroamphetamine sulfate (25% dextro)
25% dextroamphetamine saccharate (25% dextro)

So basically Adderall is 25% levoamphetamine and 75% dextroamphetamine. The L-AMP is responsible for most of the NE effect with some DA enhancing actions at higher doses, while D-AMP is preferential to DA and hits NE in higher doses.

Therefore, Adderall should be pretty balanced for NE and DA across the dose range. However, Dexedrine (D-AMP) and Vyvanse (lysine-bonded D-AMP) are preferential for DA across the entire dose range, with appreciable NE stimulation being achieved on higher doses.

Methylphenidate (Ritalin, Metadate, Concerta) on the other hand is comparatively simple.

Levomethylphenidate (L-MPH) is actually therapeutically ineffective on its own. Most of MPH's effects come from the D-MPH enantiomer (branded as Focalin). The combined DL-MPH molecule is a far stronger inhibitor of the DA transporter (DAT) than the NE transporter (NET). However, the D-MPH enantiomer is much more potent at inhibiting NET than the racemic mixture (DL-MPH) and maintains a level of DAT inhibition similar to that of the parent compound. Theoretically this will provide for more balanced stimulation of NE and DA on either Ritalin or Focalin similar to Adderall but without inducing efflux of those neurotransmitters into the synapse to the same level that Adderall does.

As a general rule, differences in effect and tolerability can be seen between Adderall/Mydayis and Dexedrine/Vyvanse. However, when it comes to the difference between Ritalin and Focalin, generally speaking they are similarly efficacious and similarly tolerable but Focalin is twice as potent by weight. So if your daily dose of Ritalin was 40mg, your daily dose of Focalin would be 20mg.

It is also worth noting that, where amphetamine-based stimulants can also cause serotonin efflux to a certain degree, methylphenidate does not appear to do this to any clinically relevant extent, but there is evidence that D-MPH binds to serotonin receptors 1A and 2B. This may or may not be beneficial for the treatment of mood symptoms, but it hasn't been studied in any great depth that I know of. That being said, it is more common than you would think for pdocs to add methylphenidate to an antidepressant to address lingering issues with anhedonia, apathy, and chronic fatigue. @Blahblah can attest to this.

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Posted (edited)

one more question, if you wouldn't mind, browri..

if lower doses of Vyvanse have more of an effect of NE, could this conceivably translate into a clinical picture involving agitation, rage, flying off the handle over minor things, seeming on the verge of relapse etc.  I ask because I have been having this issue lately at 20 mg of Vyvanse, whereas higher doses (30 and 40 mg) where (presumably) dopamine RI was involved, there seemed to be more of a calming effect, for the most part, not to say there wasn't any anxiety/agitation but it was mild in comparison.

Edited by jeva39

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No, Vyvanse and Dexedrine (both being D-AMP only) are preferential to DA and hit NE at higher doses. Adderall, containing both L-AMP and D-AMP would have more of an NE effect at all doses.

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So perhaps in my case it's more of an issue of adverse reactions associated with sensitivity to dopamine.. not NE.

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And that is very possible. NE and DA come from similar chemical precursors and it's possible that you do get some NE activity at lower doses than most. It certainly is curious.

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