I can speak towards it. I took a genetic test that tells me about my COMT genetic mutation. In my case, my dopamine and norepinephrine are elevated in my prefrontal cortex, which leads to the hyperfocus, lack of stress management, etc. The COMT gene in my case metabolizes acetylecholine very slowly. Side note, exercise and weightlifting help drain the acetylcholine for a little while. Adderall helps straighten out the dopamine signaling in the prefrontal cortex so a person feels those particular benefits. Adderall however is a weak modulator of norepinephrine.
Taking an SSRI for serotonin will also elevate your levels too much. A person might have taken Welbutrin and felt kinda off...
Taking an SNRI for norepinephrine like Strattera also again raises your/my already high norepinephrine. I came across this when I was prescribed Modafinil as an alternate ADHD treatment, and noticed my sleep was tootally jacked.
Anecdotally, I developed tinnitus when I took Welbutrin and blurry eyes when I took Modafinil. Low and behold there is some connection to both of those with norepinephrine!
I started digging down the rabbit whole into what will !reduce! norepinephrine, and it turns out another ADHD medication called Guanfacine will shuttle norepinephrine out of your prefrontal cortex and create a feedback loop to lower it. Lower norepinephrine helps you have normal conversations that are less stressful. Norepinephrine is also the main culprit in rejection sensitivity, and so on. I'm hoping at my next dr visit to ask for it..
I think I came across an abstract for a research article that made a connection where chronically elevated norepinephrine forces the alpha adrenergic receptors to tell your fat cells not to allow fat release. In normal people, norepinephrine goes up and down and normally tells fat to destroy itself.
So, while I loved the idea of Tesofensine raising Seretonin, Dopamine, and Norepinephrine; it became a hard no for me.
Instead of using Tesofensine, any other nootropics, or "head" medicines, take a look into Mirabegron (as a way to burn some extra calories while you sit). I've also found benefits in using oral testosterone (to maintain muscle mass), ezetimibe (clean the liver), cardarine (also liver), and some key supplements.
I was on HRT for a but not currently. I plan on seeing an endocrinologist soon because the GYN just randomly throws hormones at me without doing any tests. I should have much better luck with the Endocrinologist. I've also noticed MOTS-C has the opposite effect on me than most others, which seems to also be related. Every time I dig down this rabbit hole, I find more rabbit holes to explore. 
I have upped my Tirz and the fatigue has definitely hit me.
