[Disclaimer, I have no professional credentials. Just got fed up and desperate and spent a few hundred hours researching various topics online. And I have a very high stimulant tolerance. I also understand this was originally posted 6 months ago. Still relevant information]
Before tacking on more meds I would first check to see if the brand you get has been the same all along. In the U.S. most generics of amphetamine based meds (active ingredient in Vyvanse, Elvanse, Adderall, Dexedrine, etc.) hardly work compared to the good generic brands. Due to excipients (inactive ingredients) affect on crossing the Blood Brain Barrier (BBB). I do not know if the effective brands contain an adjuvant (excipient that enhances the API (Active Pharmaceutical Ingredient)) or if the low effective brands inhibit the API from crossing the BBB. Amphetamine is particularly sensitive to this effect.
Personal example from generic Adderall IR, Aurobindo (aka aurolife or sometimes this specific product is sold under the brand Northstar) at 140mg was less effective and did not last as long as 40mg of a good brand like Corepharma (discontinued), Teva, or Sandoz. Due to issues crossing the BBB. Granted, peripheral side effects did respond to the high dose which sucked.
[I wish any therapist from 2007 till 2024 had any clue about this. Would have prevented my extreme tolerance and allowed me to get off Adderall. I am sensitive to the long term side effects]
Memantine or Strattera are your best combination options.
Everyone forgot that amphetamine, one of the primary effects is as an AMPA and NMDA/glutamate agonist. Which may be even more of an effect than direct dopamine or norepinephrine effects.
Agonist means it triggers the receptor, antagonist is a blocker.
AMPA induces fast synaptic transmission
NMDA continues effect of AMPA and releases glutamate.
Glutamate is the body’s primary stimulating and modulating neurotransmitter. Simply put, it enhances synaptic transmission of dopamine (DA) and norepinephrine (NE). I believe by reducing the threshold of stimulation required to propagate a synaptic transmission. So you need less NE and DA to elicit an effect.
Problem is, NMDA/glutamate pathways are highly sensitive to overstimulation (excitotoxicity) and amphetamine happens to be really good at it.
NMDA overstimulation allows excessive flux of ions which cause dysregulation and damage from oxidative stress. Excessive glutamate is released. Excessive glutamate triggers the extrasynaptic NMDA receptor, which triggers the apoptosis (automated cell death) cascade. i.e, can kill brain cells with extrasynaptic (outside the synapse) NMDA receptors. And many researchers believe that NMDA/glutamate excitotoxicity is the primary route to long term amphetamine tolerance.
Solution, NMDA antagonism (blockers) to protect and allow time to heal pathways. Which reduces tolerance. Or, prevents tolerance if starting early.
So, memantine (an Alzheimer’s drug) is specifically made to block overexcitement of the NMDA receptor while allowing it to function at normal levels. Which regulates glutamate levels too. So, amphetamine based meds can still have their NMDA/glutamate agonism, but it is limited to non-excitotoxic levels.
Which requires a therapist who practices “evidence based” medicine. Neurologists that treat ADHD are more likely to understand this as psychiatry is more of a behavioral based discipline and pharmacology/neurology is a small part of their overall training and discipline. Plus you have to find proof which can be hard since much of the research is in the context of “abuse” and “addiction” and less on prescribed levels of amphetamines that mention it can happen at prescribed levels.
Wish I bookmarked everything which would make this post a whole lot easier to verify contents.
Strattera has a secondary dose dependent effect as a noncompetitive NMDA antagonist. (Should be easy to find that online.) It is also easier to convince a therapist as an add on as it is technically a non-stimulant. The boost to NE helps, but it also takes time to build therapeutic effect. But, the NMDA antagonism does not have to build up, it happens at each dose you take. Overtime you will need to reduce your amphetamine meds dose.
Personal experience.:
Prescribed 60mg Adderall IR which was no longer strong enough. Had taken 80mg a few times for job interviews which was a lot better but not always fully effective, just better. Started Strattera (don’t recall every dose, but last time I was on 60mg of Strattera which worked fine. Probably work for most people at lower dose. Do not know best dose for people) In less than a year I had dropped my Adderall dose to 40mg which was fully effective, and persisted when I stopped taking Strattera. Until I again built up tolerance. Did this 3 times in about 11 years. 3rd time I stayed on past 1 year and at 15 months, 40mg was too strong. Should have reduced that dose but instead stopped taking strattera. No idea where it would bottom out. But going from close but not fully effective 80mg Adderall to a too strong 40mg is more than a 50% reduction in tolerance. And shows the NMDA/glutamate agonism they stopped mentioning when dopamine became the new hot topic.
If I get the energy, maybe I’ll make a post of some supplements that may help people too.
I’ve tested for me, in the afternoon and it works. No sleeping problems at night 
I think, it’s individual, but maybe also a way for you, for a test?
since my previous doctor did not use “combi”.
)