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As soon as you realise it was never meant to be. No need to drag out a pointless relationship or be creul and end it on a day that would hurt them even more
I once waited three years out of guilt, which equated to a grand total of five years of my life WASTED! Do not be that person, e.g. me.
right now?
RUN!!!
Never
If you know that it's not working, then you need to break it off ASAP. Matters can only get worse if you don't.