title: Effects of levomilnacipran ER on fatigue symptoms associated with major depressive disorder.
abstract: The 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.
authors.affiliation: aDepartment of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts bForest Research Institute (an Allergan affiliate), Jersey City, New Jersey cPrescott Medical Communications Group, Chicago, Illinois, USA.
authors.forename: Marlene P
authors.initials: MP
authors.lastname: Freeman
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Carl
authors.initials: C
authors.lastname: Gommoll
authors.forename: Changzheng
authors.initials: C
authors.lastname: Chen
authors.forename: William M
authors.initials: WM
authors.lastname: Greenberg
authors.forename: Adam
authors.initials: A
authors.lastname: Ruth
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D017326:Clinical Trials, Phase III as Topic; D003521:Cyclopropanes / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D005221:Fatigue / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D003521:Cyclopropanes; D003692:Delayed-Action Preparations; D000078764:Milnacipran