Atomoxetine (Strattera) + Bupropion (Wellbutrin) is a treacherous ADHD combo. I don't prescribe these two together, but it may be appropriate in some situations--see Reddit comment.
DYNAMIC INTERACTION
Duplication of therapeutic effect: Both medications have the principal therapeutic mechanism of norepinephrine reuptake inhibition.
KINETIC INTERACTION
Bupropion is a strong CYP2D6 inhibitor that increases blood levels of atomoxetine.
Atomoxetine AUC increased 5.1-fold with concomitant bupropion (Todor et al, 2016).
Side effects of elevated atomoxetine may include agitation, insomnia, increased heart rate, and increased blood pressure.
According to the label, atomoxetine may be combined with a strong 2D6 inhibitor, but this is not intended for combination with a medication with the same principal mechanism of action (bupropion). For adults "initiate atomoxetine at a reduced dose of 40 mg/day when combined with strong CYP2D6 inhibitors. The dose should only be increased to the usual target dose of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated."
See Auvelity monograph which explains how CYP2D6 inHibition by bupropion can be used for therapeutic effect.
Great post! Unfortunately, patients come to me on this combo quite often. Someone will start them on wellbutrin for depression / off label ADHD, then they get ADHD dx and are started on atomoxetine target 80mg without d/c wellbutrin. There are obviously the cardiac risks with the inhibition, but they probably get used to the other side effects over time no? (not that this is a good or bad thing)... As far as long term NE inhibition x5 fold- do you feel the body compensates for having such high NE doses (fatigue etc)?