The aim of this study was to examine the longitudinal response for overall and individual symptoms during the treatment of major depressive disorder. Data were pooled from two 9-week trials, which compared duloxetine 60-mg QD (n ΒΌ 251) with placebo (n ΒΌ 261) in the treatment of MDD. Changes from baseline in the 17-item Hamilton Depression Rating Scale (HAMD 17 ) and in the Visual Analog Scales for pain were analyzed. Compared to placebo-treated patients, duloxetine-treated patients experienced greater improvement (Po.05) in the HAMD 17 total score at Week 2. The individual symptoms showing the most rapid improvements (Week 1) were depressed mood, guilt, suicidal ideation, work/activities, and psychic anxiety as well as VAS back pain and shoulder pain. At subsequent visits, significant improvements were observed in retardation (Week 2); hypochondriasis (Week 3); general somatic symptoms (Week 5); middle and late insomnia (Week 7); and gastrointestinal (GI) symptoms, genital symptoms (level of sexual interest or ease of sexual arousal), insight, and early insomnia (Week 9). Significant advantages for duloxetine were not achieved at any visit for agitation, somatic anxiety, or weight loss. At Weeks 1 and 2, placebotreated patients had significantly lower GI symptoms and reported less weight loss compared with duloxetine-treated patients; however, differences were not significant at subsequent visits. Furthermore, duloxetine was superior to placebo on GI symptoms at endpoint compared to placebo-treated patients; duloxetinetreated patients had a significantly higher response rate at Week 2 and a higher remission rate at Week 5. These results may help clinicians establish more accurate expectations regarding treatment with duloxetine. Depression and Anxiety 21:170-177, 2005.