As far a Zoloft goes it depends on the person, some people it makes tired, some it keeps them from asleep, you will just have to see how it works for you. When I was on it I took it in the morning, however my husband had to take it at night. And is this the first time you have been on Vicodin ES? Maybe it just is not working for you. You discuss that with your doctor. I would get others veiws but IME taking these two drugs should not effect their effectiveness.