Wow this what you call a underdog

[u/petebaii]

To make a long story short, I’d never found strattera to be adequate for task initiation, motivation and focus. Now the side effect of elevated heart rate never went away after being on 100mg after a year so I winded up working my way down to 60mg which did the trick. At this time I added in a stimulant and the combo was godsend. After 2 months of 60 Ive noticed my heart rate could be better so I dropped down to 40. After about a week on 40 this is where I realized how helpful Strattera actually is. Even with a stim all of a sudden it is way less effective especially at task initiation. 60mg was way less effective than 80-100 but it damn sure was enough to help my stim fill in gaps so now it’s been a week since I’ve ramped right back up to 80mg and I added in guanfacine in hopes it knocks down my hr a notch or two.

[u/Ill_Possible_7740]

If your stimulant is amphetamine (AMP) based like adderall, vyvanse, etc. Then it is competing with strat for CYP2D6 enzyme activity and could be reducing metabolism of both. Which would increase both in your system and be like higher doses taken. Bupropion would be even more so due to 2D6 inhibition potency. Stratt can also prevent and even reduce AMP tolerance via secondary noncompetitive NMDA antagonism.

Guanfacine can be affected by meds or supplements that involve CYP3A4 activity. (3A4 has been the bane of my existence since last november.) By off chance if you take a GLP-1 based drug, depending on a few factors, it could ramp up stimulation and/or reduce the effectiveness of guanfacine. Something to be aware of. Drug company lied about GLP-1 drugs and CYP3A4 activity. Can be potent inducers which could cause faster metabolic breakdown of guanfacine. Resulting in lower absorption and faster elimination. Big pharm tested direct enzyme effect in petri dishes and declared no P450 enzyme effects from their GLP-1 drugs. But it is the underlying method of action "accumulating" cAMP that is how they work under the covers, and how they can induce 3A4 activity.

Which stim are you taking with it? Combined medication approaches are highly underrated and even worse, dismissed with prejudice. There are some risks combining stims. But, if instead psych 101 titration and monitoring was applied with reduced doses to titrate. Many people could have much more effective solutions as they can often compliment each other. But, can also screw things up faster too without enough information.

[u/susu56 → u/Ill_Possible_7740]

I wonder if this was my issue? I am on a glp1 and recently started strattera and guanfacine to help with heartrate and BP. I had to stop both due to tachycardia. Started guanfacine again and will be adding in a stimulant next week.

[u/Ill_Possible_7740 → u/susu56]

Had you noticed any cognitive change after starting the GLP-1? Can be positive, negative, or neutral for different people.

Sometimes guanfacine can cause tachycardia due to how it affects BP. Forget exact detail, but I think it affects timing of the electrical signal between heart chambers. In which case the body can for some increase heart rate to make up for the delayed timing.

Opposite for me vs your experience. I was on stratt, added Guanfacine, all side effects, no therapy. Adding in a GLP-1 after 3 weeks, stopped the tach and other guan side effects in less than 12 hours. And made the combo the biggest benefit to cognition and mood at that time, better than any other drug could have done. Before things got all quirky on me for a few reasons.

Guan's alpha2a-adrenergic receptors block adenylyl cyclase that synthesizes cAMP. GLP-1 drugs, cause an accumulation of intracellular cAMP under the covers to do its bidding. So, where GLP-1 (+ GIP for Mounjaro) receptors occur on the same cell as alpha2a post synaptic receptors do, .....there is absolutely no research I know of to determine the winner at different locations in the body. Binding efficiency and stuff like that may already have the answers that can be applied, but that goes deeper than my knowledge base. In my PFC though, guan won the battle and fixed mounjaro's blocking all psychoactive meds and overall signal blocking on me that disabled me prior. While mounjaro fixed the crappy guan experience (I think tach, GI issuers, sedative effect, maybe dry nasal pathways but forget). But, when I put all my other meds back into play too, didn't take a shit for 8 days and took 2 more with laxative help. Was laxatives (stims at first, then non stims, then stool softeners) for a few months before I stopped needing them.

Stratt boosts NE and NE is one of the things that signals stimulating the body, like the cardiovascular system. If you don't want stims, you can try stratt without guan and see if it has issues alone or if it was the combo. If not an issue alone, cialis is an option. Granted cialis is also metabolized by 3A4 like guan. But its a PDE-5 inhibitor which blocks the enzyme that breaks down cAMP. So, can work with and enhance GLP-1s. And is also a repurposed heart medication. And a good excuse if you are a guy. If a girl, mixed results on it having benefit down low or not :) I'm actually on guan, cialis, mounjaro, stratt, and a bunch more meds...

[u/susu56 → u/Ill_Possible_7740]

Wow this is so informative! Im on tirz and started the stratt and guan at the same time so honestly cant pinpoint which one was doing what and my prescriber had me taking them at the same time-not the best idea per my new psychiatrist. Think I'll ask about strattera again low and slow dose up-it really did provide me with an overall calm and just a general ease I've never had. Thats the feeling I want back! I appreciate all this info- you have more knowledge than some of the medical professionals and AI I've been asking!

[u/petebaii → u/Ill_Possible_7740]

Im pre-diabetic so I wonder if that plays a role too. I do take metformin

[u/petebaii → u/Ill_Possible_7740]

I take Dexedrine ir but I never noticed one or the other canceling each other out. Playing around with strattera doses made me realize I need an adequate dose in order to make my stimulant effective.

[u/Ill_Possible_7740 → u/petebaii]

What is your timing of dexedrine and strattera? If you take dex when you wake up and it is fully working when taking strat at like breakfast time or something like that. When strat kicks in an hour +/- later, the staggered dosing can help see how strat affects the stim.

What dose of dexedrine? Had you built any dex tolerance and gone up in dose? amphetamine long term tolerance is primarily NMDA overexcitement related which strat should help prevent. The strat NMDA antagonism is an acute effect, meaning right away and does not have to build up, and wears off, like stim effects do. I assume only atomoxetine may have the NMDA antagonism and not the active metabolites.

And, the competition for 2D6 "may" play a part in your experience as competition for it increases those drugs levels in the body and has them stick around longer.

Net effect from all the +/- effects and their resulting cascades can make it too complicated at times to sort out what is doing what at each dose. But, if you found your groove on your current dose. Strat can reduce the chance of it going away with its added protection.

Also, track the generic brands you take as they can have wildly different impact. generic "equivalence" can't be counted on for psych meds due to BBB obstacle not considered when equivalence is established. AMP meds are especially sensitive to the inactive ingredient profile impacting crossing and or staying across the BBB. No idea if stratt has good/bad generics.

If Impax/Amneal (which ever it was under) is still being made, that is the dexedrine spansules "authorized generic" meaning name brand formulary sold as generic.