The objective of this study was to assess the relationship between early changes in anxiety/somatization symptoms and treatment outcome among major depressive disorder patients during a 12-week trial of fluoxetine. We also examined the relationship between anxious depression and treatment response. Five hundred and ten major depressive disorder patients received 12 weeks of fluoxetine with flexible dosing [target dosages: 10 mg/day (week 1), 20 mg/day (weeks 2-4), 40 mg/day (weeks 4-8), and 60 mg/day (weeks 5-12)]. We assessed the relationship between early changes in 17-item Hamilton Rating Scale for Depression (HAMD-17)-anxiety/somatization factor items and depressive remission, as well as whether anxious depression at baseline predicted remission at study endpoint. Baseline HAMD-17 scores were considered as covariates and the Bonferroni correction (P < or = 0.008) was used for multiple comparisons. Adjusting for baseline HAMD-17 scores, patients who experienced greater early improvement in somatic symptoms (gastrointestinal) were significantly more likely to attain remission (HAMD-17 <8) at endpoint than those without early improvement (P=0.006). Early changes in the remaining items did not predict remission, nor did anxious depression at baseline. In conclusion, among the anxiety/somatization factor items, only early changes in somatic symptoms (gastrointestinal) predicted remission. Future studies are warranted to further investigate this relationship as well as that between anxious depression and treatment outcome.