levomilnacipran and Depressive-Disorder--Major

The primary objective of this narrative review is to provide clinicians an in-depth analysis of the mechanism of action, pharmacokinetics, toxicology, and efficacy of levomilnacipran. We propose that unlike selective serotonin reuptake inhibitors (SSRIs), or even their precursor serotonin-norepinephrine reuptake inhibitors (SNRIs), levomilnacipran demonstrates a potentially unique ability to alleviate the fatigue symptom cluster of major depressive disorder (MDD).. A literature review was completed in PubMed using the MeSH term levomilnacipran.. Inclusion criteria were English-language only, randomized controlled trials and systematic reviews published through March 2019. Analyses using product labels and anecdotal or uncontrolled reports of clinical applications were excluded. Only published data from short-term and long-term trials were analyzed. The search resulted in 73 articles. The evidence-based review comprises a total of 31 articles.. The data analyzed suggest that levomilnacipran has evidence in the treatment of MDD. More specifically, data suggest that levomilnacipran may be unique among SSRI and SNRI antidepressants in its ability to improve the fatigue symptom cluster in MDD.. Further investigations are warranted into levomilnacipran's potentially unique ability to alleviate the fatigue symptom cluster of MDD. Future head-to-head studies and studies that assess for clinically relevant improvements in fatigue are needed.

Topics: Depressive Disorder, Major; Humans; Levomilnacipran; Serotonin and Noradrenaline Reuptake Inhibitors

Late-life depression (LLD) is associated with significant medical comorbidity, cognitive impairment, and suboptimal treatment response compared to depression experienced earlier in life. Levomilnacipran (LVM) is a novel antidepressant the effects of which on neuroplasticity have not yet been investigated. We investigated the effect of LVM on cortical thickness in a pilot randomised placebo-controlled trial in LLD.. Twenty-nine adults (≥ 60 years) with major depression (48.3% female; mean age = 71.5 ± 5.8 years; mean education = 16.0 ± 1.7 years) were randomised to either LVM or placebo for 12 weeks. T1-weighted images were acquired at baseline and 12 weeks. Thirteen subjects (six LVM and seven placebo) completed the study. Group differences in cortical thickness change across the study period were evaluated, with age and total intracranial volume included as covariates.. Dropout rates did not differ significantly between groups. The LVM group had significantly more side effects, but no serious adverse events were reported. Lower LVM dose (≤ 40 mg) was better tolerated than higher doses (80-120 mg). Additionally, the LVM group showed a larger increase in cortical thickness in the right postcentral gyrus (primary somatosensory), supramarginal gyrus (sensory association region), and lateral occipital cortex (visual cortex) compared to the placebo group and greater reductions in the left insula.. LVM may be less tolerable by older adults with depression and the effects on cortical thickness across sensory and sensory association regions may be related to the experience of side effects. Larger studies are necessary to evaluate treatment efficacy, tolerability, and neural effects of LVM in LLD.

Topics: Aged; Antidepressive Agents; Cerebral Cortex; Depression; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Levomilnacipran; Magnetic Resonance Imaging; Male; Pilot Projects; Psychiatric Status Rating Scales; Treatment Outcome

Levomilnacipran extended release (ER) is a serotonin and norepinephrine reuptake inhibitor approved for major depressive disorder (MDD) in adults. This study was designed to evaluate relapse prevention with levomilnacipran ER in patients with MDD.. Patients (≥18 years) with MDD (N = 644) received 20 weeks of open-label treatment with levomilnacipran ER 40, 80, or 120 mg/d (8 weeks flexible dosing; 12 weeks fixed dosing). Patients with a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤12 from the end of week 8 to week 20 were randomized to 26 weeks of double-blind treatment with levomilnacipran ER (same dosage; n = 165) or placebo (n = 159). The primary efficacy endpoint was time to relapse, defined as insufficient therapeutic response (≥2-point increase from randomization in Clinical Global Impression of Severity score, risk of suicide, need for hospitalization due to worsening of depression, or need for alternative antidepressant treatment as determined by the investigator) or an MADRS total score ≥18 at 2 consecutive visits.. In the double-blind intent-to-treat population, levomilnacipran ER-treated patients had a significantly longer time to relapse compared with placebo (hazard ratio = 0.56; 95% CI, 0.33-0.92; P = 0.0212). Crude relapse rates were 14.5% (levomilnacipran ER) and 24.5% (placebo). Double-blind treatment-emergent adverse events (AEs) were reported for 58.8% and 56.0% of levomilnacipran ER and placebo patients, respectively; 3.0% and 1.3% discontinued due to AEs, and 1.2% and 0.6% had serious AEs, respectively.. Levomilnacipran ER (40-120 mg/d) was effective in preventing relapse in patients with MDD. Safety and tolerability results were consistent with levomilnacipran ER acute studies.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Levomilnacipran; Male; Middle Aged; Recurrence; Secondary Prevention; Serotonin and Noradrenaline Reuptake Inhibitors; Suicide; Treatment Outcome; Young Adult

Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Levomilnacipran; Schizophrenia

Topics: Antidepressive Agents; Cost-Benefit Analysis; Depressive Disorder, Major; Humans; Levomilnacipran; Quality-Adjusted Life Years; Treatment Outcome; Vilazodone Hydrochloride; Vortioxetine

To evaluate the effects of levomilnacipran extended-release (ER) on suicidal ideation and behavior in adults with major depressive disorder (MDD).. Post hoc analyses were conducted in patients from 4 randomized, double-blind, placebo-controlled trials and a long-term, open-label extension study of levomilnacipran ER (40-120 mg/d) in adults with MDD. Analyses included incidence of suicide-related treatment-emergent adverse events (TEAEs); incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation (score=1-5) and behavior (score=6-10); percent of patients who shifted from no C-SSRS suicidal ideation/behavior at baseline to suicidal ideation during treatment (worsened from score=0 to score=1-5), or vice-versa (improved from score=1-5 to score=0).. Suicide-related TEAEs occurred in<1% of patients in the levomilnacipran ER studies. The incidence of C-SSRS suicidal ideation was 22.2%, 23.9%, and 21.7% for placebo, short-term levomilnacipran ER, and long-term levomilnacipran ER, respectively; C-SSRS suicidal behavior was<1% in all of these groups. In the short-term studies, the percentage of patients with C-SSRS shifts were as follows: worsening from score=0 to score=1-5 (placebo, 8.6%; levomilnacipran ER, 11.0%); improvement from score=1-5 to score=0 (placebo, 24.0%; levomilnacipran ER, 27.7%).. In adult MDD patients, the incidence of suicidal ideation and behavior was similar between placebo and short-term levomilnacipran ER as indicated by TEAE reports and C-SSRS scores. Worsening in C-SSRS scores was also similar between placebo and levomilnacipran ER. There was no indication of increased suicidality during longer courses of continued therapy. Together, these findings suggest that this medication is not associated with increased risks of suicidal ideation or behavior.

Topics: Antidepressive Agents; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Depressive Disorder, Major; Double-Blind Method; Humans; Levomilnacipran; Randomized Controlled Trials as Topic; Suicidal Ideation; Suicide