You’re never gonna fully attnuate all the edge cases and it doesn’t really matter that some people end up being “allergic” or oversensitive or undersensitive to it. Thats what titration and medical supervision are for, not everything works for everyone.
Thats why choice and second/third/fourth line etc treatments exist. I sometimes do wonder if you did a double blind with folks and didn’t tell them, I would conjecture the hyper-extended nature of such things if that were so established could be sufficient to mitigate for individual differences in metabolic-polymorphism or whatever