Does zoloft (sertraline) make you feel worse at the beginning and then better in the long run?

It can.: Zoloft (sertraline) belongs to a family of antidepressants called selective serotonin reuptake inhibitors (ssris). Initially there can be intestinal upset and headache. By increasing a low dose slowly to desired level helps. For some, their mood lifts quickly but recommendations encourage a 6-week trial before deciding effectiveness. However, changes are made sooner if depression/anxiety worsen.