It has to do with a chemical reaction between Tramadol/Ultram and any antidepressant...over a period of time. There is a lot of information on the internet regarding this subject. I know my friends doctor says because Tramadol is a fairly new synthetic he doesn't prescribe it for his patients that are on other drugs because interaction with other drugs is largely unknown however apparently mixing it with an antidepressant is not a good idea.