What is defined as noteworthy harm? Are we talking about noteworthy short-term effects or as far on the spectrum as death?

I can think of quite a few substance which result in harm with sudden cessation after prolonged usage -- Alcohol, benzodiazapines, antihypertensives, etc.. Perhaps medications like: antipsychotics, anticonvulsants, immunosupressants, etc. as well?

Obviously individual reactions vary and nothing is a guarantee in medicine, but I believe many substances can cause noteworthy issues with sudden cessation that are greater than just the reemergence of the underlying condition being treated. However I am probably more wrong than right on most topics, so (anyone) feel free to correct me if I am mistaken.