Freeman, MarleneFava, MaurizioGommoll, CarlChen, ChangzhengGreenberg, William M.Ruth, Adam2016-03-012016Freeman, Marlene P., Maurizio Fava, Carl Gommoll, Changzheng Chen, William M. Greenberg, and Adam Ruth. 2016. “Effects of levomilnacipran ER on fatigue symptoms associated with major depressive disorder.” International Clinical Psychopharmacology 31 (2): 100-109. doi:10.1097/YIC.0000000000000104. http://dx.doi.org/10.1097/YIC.0000000000000104.0268-1315http://nrs.harvard.edu/urn-3:HUL.InstRepos:25658426The aim of this study was to evaluate the effects of levomilnacipran extended-release (ER) on depression-related fatigue in adults with major depressive disorder. Post-hoc analyses of five phase III trials were carried out, with evaluation of fatigue symptoms based on score changes in four items: Montgomery–Åsberg Depression Rating Scale (MADRS) item 7 (lassitude), and 17-item Hamilton Depression Rating Scale (HAMD17) items 7 (work/activities), 8 (retardation), and 13 (somatic symptoms). Symptom remission was analyzed on the basis of score shifts from baseline to end of treatment: MADRS item 7 and HAMD17 item 7 (from ≥2 to ≤1); HAMD17 items 8 and 13 (from ≥1 to 0). The mean change in MADRS total score was analyzed in patients with low and high fatigue (MADRS item 7 baseline score <4 and ≥4, respectively). Patients receiving levomilnacipran ER had significantly greater mean improvements and symptom remission (no/minimal residual fatigue) on all fatigue-related items: lassitude (35 vs. 28%), work/activities (43 vs. 35%), retardation (46 vs. 39%), somatic symptoms (26 vs. 18%; all Ps<0.01 versus placebo). The mean change in MADRS total score was significantly greater with levomilnacipran ER versus placebo in both low (least squares mean difference=−2.8, P=0.0018) and high (least squares mean difference=−3.1, P<0.0001) fatigue subgroups. Levomilnacipran ER treatment was effective in reducing depression-related fatigue in adult patients with major depressive disorder and was associated with remission of fatigue symptoms.en-USage factorsantidepressantclinical trialdepressionlassitudesex factorsJournal Article2016-03-0110.1097/YIC.0000000000000104