• Maurizio Fava, Craig H Mallinckrodt, Michael J Detke, John G Watkin, and Madelaine M Wohlreich.
• Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
• J Clin Psychiatry. 2004 Apr 1;65(4):521-30.

BackgroundDepression is a chronic disease consisting of emotional/psychological and physical symptoms. Emotional symptoms have been shown to respond to currently available antidepressants; however, physical symptoms may not be as responsive. It was hypothesized that resolution of both psychological and physical symptoms of depression would predict a higher percentage of patients achieving remission.MethodEfficacy data were pooled from 2 identical, but independent, 9-week randomized, double-blind clinical trials of duloxetine 60 mg q.d. (N = 251) and placebo (N = 261). All patients met diagnostic criteria for DSM-IV major depressive disorder, which was confirmed by the Mini-International Neuropsychiatric Interview. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, the HAM-D-17 Maier subscale, the Clinical Global Impressions-Severity of Illness (CGI-S) scale, the Patient Global Impression of Improvement (PGI-I) scale, the Somatic Symptom Inventory, the Quality of Life in Depression Scale, and Visual Analog Scales (VAS) for pain (overall pain, headaches, back pain, shoulder pain, interference with daily activities, and time in pain while awake).ResultsDuloxetine-treated patients demonstrated significantly greater improvement in overall pain (p =.016), back pain (p =.002), and shoulder pain (p =.021) at week 9 compared with patients receiving placebo. When treatment effects were pooled over all visits, patients receiving duloxetine, 60 mg q.d., exhibited significantly greater improvement than placebo-treated patients in 5 of the 6 assessed VAS pain measures. Approximately 50% of the improvement in overall pain was independent of improvement in HAM-D-17 total score. Assuming the same level of improvement in core emotional symptoms of depression (Maier subscale), improvement in overall pain severity was associated with higher estimated probabilities of remission (p <.001). The week 9 means for VAS overall pain severity were 13.0 for remitters (last observed value for HAM-D-17 was < or = 7) compared with 22.7 for nonremitters (p <.001), respectively, representing a greater than 3-fold improvement from baseline in remitters. The remission rate for pain responders (improvement in VAS overall pain from baseline to last observation > or = 50%) was twice that observed for pain nonresponders (36.2% vs. 17.8%, p <.001). Greater improvements in pain outcomes were associated with more favorable endpoint outcomes on the CGI-S and PGI-I scales. In addition, early favorable responses in VAS overall pain severity were associated with favorable endpoint outcomes.ConclusionsTreatment with duloxetine, 60 mg q.d., significantly reduced pain compared with placebo. Improvements in pain severity were attributable equally to the direct effect of duloxetine and to associated changes in depression severity. Improvement in painful physical symptoms was associated with higher remission rates even after accounting for improvement in core emotional symptoms.

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