Trial reportJournal of psychiatry & neuroscience : JPN2014
Levomilnacipran ER 40 mg and 80 mg in patients with major depressive disorder: a phase III, randomized, double-blind, fixed-dose, placebo-controlled study.
Trial report in Journal of psychiatry & neuroscience : JPN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01377194 (A Double-blind, Placebo-Controlled, Fixed-Dose Study of Levomilnacipran SR in Patients With Major Depressive Disorder), which is not on this map. Cited by 31 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Double-blind, Placebo-Controlled, Fixed-Dose Study of Levomilnacipran SR in Patients With Major Depressive Disorder
Who cites it
31 citing papers in PubMed, 3 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Evidence on antidepressant withdrawal: an appraisal and reanalysis of a recent systematic review.Psychological medicine · 2025Pooled it
- Selective publication of antidepressant trials and its influence on apparent efficacy: Updated comparisons and meta-analyses of newer versus older trials.PLoS medicine · 2022Pooled it
- Pooled it
- Relapse prevention with levomilnacipran ER in adults with major depressive disorder: A multicenter, randomized, double-blind, placebo-controlled study.Depression and anxiety · 2019Trial
- Evaluation of Cytochrome P450 (CYP) 3A4-Based Interactions of Levomilnacipran with Ketoconazole, Carbamazepine or Alprazolam in Healthy Subjects.Clinical drug investigation · 2015Trial
- Efficacy of levomilnacipran extended-release in major depressive disorder: pooled analysis of 5 double-blind, placebo-controlled trials.CNS spectrums · 2015Trial
- Disposition and metabolism of [14C]-levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, in humans, monkeys, and rats.Drug design, development and therapy · 2015Trial
- Effect of renal impairment on the pharmacokinetics of levomilnacipran following a single oral dose of levomilnacipran extended-release capsule in humans.Drug design, development and therapy · 2015Trial
- Efficacy of levomilnacipran extended-release in improving functional impairment associated with major depressive disorder: pooled analyses of five double-blind, placebo-controlled trials.International clinical psychopharmacology · 2014Trial
- Effect of hepatic impairment on the pharmacokinetics of levomilnacipran following a single oral dose of a levomilnacipran extended-release capsule in human participants.Clinical drug investigation · 2014Trial
- A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder.Journal of clinical psychopharmacology · 2014Trial
- The efficacy of extended-release levomilnacipran in moderate to severe major depressive disorder: secondary and post-hoc analyses from a randomized, double-blind, placebo-controlled study.International clinical psychopharmacology · 2014Trial
- Safety and tolerability of levomilnacipran ER in major depressive disorder: results from an open-label, 48-week extension study.Clinical drug investigation · 2013Trial
- Disproportionality analysis of safety signals for milnacipran and levomilnacipran: a pharmacovigilance study using the FDA adverse event reporting system.Frontiers in pharmacology · 2025Article
- Recent advances in the synthesis of antidepressant derivatives: pharmacologic insights for mood disorders.3 Biotech · 2024Review
- Recent Developments in Pharmacotherapy of Depression: Bench to Bedside.Journal of personalized medicine · 2023Review
- The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2023Article
- Practical pathway for the management of depression in the workplace: a Canadian perspective.Frontiers in psychiatry · 2023Review
- The clinical utility of newer antidepressant agents: Understanding the role in management of MDD.The mental health clinician · 2022Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMajor 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.
methodsThis 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 18-75 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-Åsberg 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.
resultsThe 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%-83%). 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 (-3.3 [-5.5 to -1.1], p = 0.003) and 80 mg/day (-3.1, [-5.3 to -1.0], p = 0.004). On SDS change from baseline the LSMD (and 95% CI) versus placebo was also significant for levomilnacipran ER 40 mg/day (-1.8, 95% [-3.6 to 0], p = 0.046) and 80 mg/day (-2.7 [-4.5 to -0.9], p = 0.003). More patients in the levomilnacipran ER than the placebo group prematurely exited the study owing to adverse events; common adverse events (≥ 5% and ≥ double the rate of placebo) were nausea, dry mouth, increased heart rate, constipation, dizziness, hyperhidrosis, urinary hesitation and erectile dysfunction. LIMITATIONS: Limitations to our study included short treatment duration and lack of an active control arm.
conclusionLevomilnacipran 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. CLINICAL
trial registrationNCT01377194.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.