OBJECTIVE This study describes a single-site investigation on the effects of a randomized double-blind placebo trial targeting duloxetine added to opioid use (duloxetine + opioid) against a comparator (placebo + opioid) in spine surgery patients, independent of major depression. METHODS The double-blind comparator study assessed two groups on opioids: one using duloxetine and the other a placebo. Subjects were administered the respective medication 2 weeks prior to surgery and continued on this for more than 3 months. Subjects were assessed at three times: prior to surgery, 4 weeks postsurgery, and 12 weeks postsurgery. They completed a battery of tests assessing for pain, adjustment, and psychiatric problems. METHODS Neurosurgical outpatient and inpatient setting. METHODS Sixty-eight patients completed the study. They received one of three types of elective spine surgery. METHODS Subjects were given duloxetine or placebo 2 weeks prior to surgery and continued with the regimen for more than 3 months. RESULTS The primary focus was pain and second on adjustment factors and psychiatric symptoms: depression and anxiety. The amount of opioid use presurgery and postsurgery was also evaluated. RESULTS There were differences among the groups on Brief Pain Inventory (BPI)-Average, the core pain marker, and BPI-Sleep. Within-subject analyses showed that duloxetine subjects improved significantly from baseline. For function, post-CIBIC and post-Functional Adjustment Questionnaire were significant, favoring duloxetine. Reduction of opioid use was not a factor; both groups' utilization declined. For affect, both groups were significantly improved over time. CONCLUSIONS Duloxetine seems to improve pain, assist with maintaining function, and reduce intensity of affect.