Antidepressants, including serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, are widely used in the United States despite a number of unknowns related to their clinical performance. One of the biggest unknowns stems from the dearth of evidence on the efficacy of the drugs over the long term, as most studies have followed up with participants for only 8 to 12 weeks. Researchers also do not know much about how antidepressants affect mental and physical quality of life over time.