Painful physical symptoms are common features of major depressive disorder and may be the presenting complaints in primary care settings. The effect of the dual serotonin (5-HT) and norepinephrine reuptake inhibitor duloxetine on emotional and painful physical symptoms in outpatients with major depressive disorder was evaluated in three randomized, double-blind, placebo-controlled trials. The trials' primary objective was to evaluate the effect of duloxetine on mood, and subjects were not enrolled on the basis of presence, type, or severity of pain. However, the pain-relieving effects of duloxetine were evaluated by a priori defined analyses of results from a visual analogue scale and the Somatic Symptom Inventory. Compared with placebo, duloxetine was associated with significant reduction in pain severity. The authors concluded that duloxetine reduces the painful physical symptoms of depression.