Most patients with major depressive disorder (MDD) have symptoms of anxiety associated with their depression. Duloxetine, a potent and balanced dual serotonin and norepinephrine reuptake inhibitor, is effective in the treatmentof depression. We investigated its effects in treating the symptoms of anxiety in depressed patients. This investigation includes all the placebo-controlled studies of duloxetine in MDD but focuses on four trials in which duloxetine was superior to placebo on the primary outcome measure of the 17-item Hamilton Depression Rating Scale (HAMD17) total score. Studies 1 and 2 included duloxetine at 60 mg/d (the recommended starting and therapeutic dose) and placebo. Study 3 included duloxetine 120 mg/d (administered as 60 mg b.i.d.), fluoxetine 20 mg/d, and placebo. Study 4 included duloxetine 40 mg/d (administered as 20 mg b.i.d.), duloxetine 80 mg/d (administered as 40 mg b.i.d.), paroxetine 20 mg/d, and placebo. Anxiety was assessed in all studies using the HAMD anxiety/somatization subfactor and the anxiety-psychic item (HAMD Item 10). Studies 3 and 4 also included the Hamilton Anxiety Rating Scale (HAMA). Across the four studies, duloxetine at doses of ≥60 mg was compared with placebo on 10 outcomes and with either paroxetine or fluoxetine on 6 outcomes. In 8 comparisons, mean improvement for duloxetine was significantly greater than placebo at the last study visit and/or across all study visits. In 3 comparisons, the mean improvement for duloxetine was significantly greater than paroxetine or fluoxetine. In these studies, duloxetine provided rapid relief of anxiety symptoms associated with depression. Previous reports have summarized duloxetine's efficacy in treating the core emotional symptoms and painful physical symptoms associated with depression. Duloxetine's efficacy in treating a broad spectrum of symptoms associated with depression, including mood, anxiety, and painful physical symptoms, may be attributed to dual reuptake inhibition of both serotonin and norepinephrine. Efficacy in these three key symptom domains may in turn explain the high probabilities of remission (43–57%) observed in these studies. Depression and Anxiety 18:53–61, 2003. © 2003 Wiley-Liss, Inc.