Stimulants Extended release formulations act as instant release, effects wear off after 2-3 hour

[Zeon]

Pretext: Have ADHD diagnosis, using these drugs on an on demand basis to study instead of taking them daily. Doctor knows about this and is ok with it. I switch between lysdexamfetamine and extended release formuations of methylphenidate, referred to here as "XR".

As of lately stimulants just really don't last as long for me. I've been on/off them for years and even when I grew a huge tolerance to them and needed 100mg of lysdexamfetamine to study, the long-lasting effects of the drug were still there. Whenever tolerance developed, the effects would be less strong... but the duration of the drug would be the same, if that makes sense. Nowadays, lysdexamfetamine/XR methylphenidate last, tops, 3-4 hours. I'm a fast metabolizer, but normally these drugs last 6-8 hours for me. I am also a very good responder, and 30mg lysdexamfetamine/20mg methylphenidate works great for me. Lately however, after an hour or so I get a huge rush, then after 3-4 hours or even less, I crash, can't concentrate for shit and get really hungry. It's as if extended release is acting as immediate release, if that makes sense? Upon consultation with my doctor she just keeps suggesting to up the dose more and more, which does nothing for the duration of it. At the same time, I'm afraid of redosing these drugs after 3-4 hours because I know the drug is still in my system. My doctor has also suggested switching to IR methylphenidate, but the idea of having to take a pill every 3 hours after I crash isn't appealing to me at all.

 

[Scrofula]

I am . . . less than clear on your effects and complaints. You're telling me that your extended-release me-phen. and the slow-to-activate lisdex., give you a "huge rush" that lasts for 3-4 hours before a crash? Yes, OK, sorry, that's your whole point; I agree that's more like regular amphetamine or IR me-phen. I agree that simply increasing the dosage wouldn't prolong the duration. It is also probably not the greatest idea to redose the lisdex that quickly, since it has a good hour lag for conversion, and a generally XR-profile..

I think it's a little weird to take XR drugs on a prn-basis though. If you were a good studious collegiate, you'd only need a single me-phen. IR before your evening scholarship. THen again, if you feel the XR as a "huge rush" you might find the IR too intense.

Now, is your doc fully aware of your exact timing of these two drugs? Because to me, timing is crucial. I don't obviously understand how these two interact with each other, but they will interfere to some extent. Have you at all considered either of these drugs by themselves? Try just the lisdex in the am/afternoon for a while, then just the me-phen in the afternoon, and see what the subjective differences are. I can see some bizarre biochemical magic at work that cause an initial synergy and a later early termination.

"Technical" argle below:

Now, I'm confused, because to me, methylphenidate should block the activity of amphetamine (and therefore lisdexamph too), and yet I know that they are occasionally prescribed together by people smarter than me.

It's a simplistic view--I know that amph can simply diffuse into presynaptic neurons and doesn't need the dopamine transporter (DAT) to get in. But dopamine release by amphs is about reversing DAT direction, and at least according to the little picture on wikipedia, when amphs aren't reversing DAT, they're causing it's internalization. Yeah, there're other effects like decreasing firing rate, which is directly at odds with methylphenidate's general increase in firing rate.

The DAT stuff I mention, because methylphenidate's mechanism is about binding and inhibiting DAT. Seems like it's hard to do that if the receptor's been internalized, or running backwards; or maybe it prevents DAT reversal/internalization, in which case again, why bother with the amphetamine?

It's a similar story over at the adrenergic side. I don't see the rationale for these two together--think about it, if they didn't interfere, the combo would probably be a major seizure/adrenergic storm/cheese effect/neuroleptic malignant syndrome risk, the catecholamine side of serotonin syndrome--releasing dopamine (and norepi) by the bucketfull and preventing it's reuptake. That there aren't red flags everywhere, or even a note, suggests they interfere with each other pretty hard, outside of subtleties that may be beneficial for niche cases.

 

[Lorne???]

^ yeah that makes little sense(co-prescribing those, then again they give serotinergics w/ serotonin antagonists, so who knows?)

XR medications can be unreliable, due to dose dumping and variations in release, and correspondingly AUC- and Lisdexamp-wtf is a prodrug as Scrofula mentioned, these are both odd options PRN, and together, there is potential for side effects, and they partially offset each other?s actions

One thing Scrofula didn?t mention was that duration is partially dose dependent, thought this is more so with IR medications, I think, and would not recommend upping the dose; as you do these medications in combination will likely become less effective and you increase chance of side effects

And Lisamp is pretty solid, in that it isn?t your typical codiene type prodrug-more like Tranxene, it will pretty much convert more or less fully and with consistentcy

Would cut one, and try what Scrofula mentioned- this combo isn?t working for you, and there are reasons not to take them together anyway

 

[Scrofula]

I read the lisdex (Vyvanse) PI and they discuss dramatic hematocrit levels maintaining conversion. IOW, according to that sheet that comes with your meds and most people throw away, you could be bleeding out from multiple gunshots and still expect amphetamine to come out (your red blood cells do the conversion of lisdex to amphetamine). They didn't mention if the reaction got slowed down though (which means it was).

Point being that lisdex profile is pretty steady. That does NOT mean that the stuff it does in your brain will be steady if you add a conflicting drug.

And like Lorne said, extended-release drugs are usually a gimmick, and you have extra gelatin to dissolve, or a little cotton plug that expands and shoves the drugs out through a mini colander-type deal. There's a lot of ways that can get sabotaged, as any pill-favoring bluelighter can tell you.

But I still think that the amphs hit your brain first, flip the transporter and dump a bunch of dopamine, only for the me-phen. to slowly arrive and start clogging up those transporters, till they eventually kill the effects.

Or something.

Anyway, a better analogy, Lorne, isn't with serotonergics. A lot of those are reuptake inhibitors, along with a receptor agonist or antagonist. Like turning up the volume in the synapse at the same you fiddle with a single channel. This is more like trying to time your MDMA and your Prozac just right, and expecting to be twice as normal.

 

[Lorne???]

Yeah that wasn't a great analogy in my part, and not explained, which have made it pointless anyway

Like the Prozac and MDMA, that's about 4 stars

Yeah, didn't get someone saying that lisamp didn't work or something, it's converted in blood-don't know the detauls(although just got a better idea) however it would be akin to heroin not delivering MAM/morphine into the CNS

Gunsgot wounds, that is extreme-guess it gives you an amphhetamine that will work even at the corral

 

[Zeon]

Thanks for the replies guys. I am not taking lysdexamfetamine together with methylphenidate on any one day, that would be very dangerous and I don't think a doctor would ever advocate that. I can see how the post was confusing though. What I'm trying to say is that I alternate between them.