{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:05:43Z","timestamp":1775041543992,"version":"3.50.1"},"reference-count":29,"publisher":"Canadian Science Publishing","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Psychiatry Neurosci"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> Major depressive disorder (MDD) is a global health concern. This study examined the efficacy, safety and tolerability of an extended-release (ER) formulation of levomilnacipran, an antidepressant approved for the treatment of MDD in adults. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p> This 10-week (1-week placebo run-in period, 8-week double-blind treatment, 1-week down-taper), multicentre, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted between June 2011 and March 2012. Adult outpatients (age 18\u201375 yr) with MDD were randomly assigned (1:1:1) to placebo or to levomilnacipran ER 40 mg\/day or 80 mg\/day. For primary efficacy, we analyzed the Montgomery\u2013\u00c5sberg Depression Rating Scale (MADRS) change from baseline to week 8 using a mixed-effects model for repeated-measures approach on the intent-to-treat (ITT) population. For secondary efficacy, we used the Sheehan Disability Scale (SDS), and for safety, we examined adverse events and laboratory, vital sign\/physical and electrocardiography findings. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> The ITT population consisted of 185 patients in the placebo group, 185 in the levomilnacipran ER 40 mg\/day group and 187 in the levomilnacipran ER 80 mg\/day group. Study completion rates were similar among the groups (76%\u201383%). On MADRS change from baseline the least squares mean difference (LSMD) and 95% confidence interval (CI) versus placebo was significant for levomilnacipran ER 40 mg\/day (\u20133.3 [\u22125.5 to \u22121.1], p = 0.003) and 80 mg\/day (\u22123.1, [\u22125.3 to \u22121.0], p = 0.004). On SDS change from baseline the LSMD (and 95% CI) versus placebo was also significant for levomilnacipran ER 40 mg\/day (\u22121.8, 95% [\u22123.6 to 0], p = 0.046) and 80 mg\/day (\u22122.7 [\u22124.5 to \u22120.9], p = 0.003). More patients in the levomilnacipran ER than the placebo group prematurely exited the study owing to adverse events; common adverse events (\u2265 5% and \u2265 double the rate of placebo) were nausea, dry mouth, increased heart rate, constipation, dizziness, hyperhidrosis, urinary hesitation and erectile dysfunction. <\/jats:p><\/jats:sec><jats:sec><jats:title>Limitations:<\/jats:title><jats:p> Limitations to our study included short treatment duration and lack of an active control arm. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p> Levomilnacipran ER at doses of 40 mg\/day and 80 mg\/day demonstrated efficacy on symptomatic and functional measures of MDD and was generally well tolerated in this patient population. <\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p> NCT01377194. <\/jats:p><\/jats:sec>","DOI":"10.1503\/jpn.130040","type":"journal-article","created":{"date-parts":[[2014,1,6]],"date-time":"2014-01-06T10:32:24Z","timestamp":1389004344000},"page":"40-49","source":"Crossref","is-referenced-by-count":50,"title":["Levomilnacipran ER 40 mg and 80 mg in patients with major depressive disorder: a phase III, randomized, double-blind, fixed-dose, placebo-controlled study"],"prefix":"10.1139","volume":"39","author":[{"given":"David","family":"Bakish","sequence":"first","affiliation":[{"name":"Ottawa Psychopharmacology Clinic, Ottawa, Ont., Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anjana","family":"Bose","sequence":"additional","affiliation":[{"name":"Forest Research Institute, at time of study, Jersey City, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl","family":"Gommoll","sequence":"additional","affiliation":[{"name":"Forest Research Institute, Jersey City, NJ, 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