Fetzima (levomilnacipran ER) / Pierre Fabre, AbbVie - LARVOL DELTA

Comparative efficacy of antidepressants for acute adolescent major depressive disorder: a source-verified systematic review and network meta-analysis. (PubMed, Front Psychiatry) - "The antidepressant-only primary SMD network contained 4 parent trials and 11 randomized arms, including desipramine, amitriptyline, fluoxetine, levomilnacipran 40 mg, levomilnacipran 80 mg, vilazodone 15 mg, vilazodone 30 mg, and pill placebo. The only statistically significant estimate was derived from a small historical desipramine trial with important data-quality limitations. Adolescent-specific arm-level evidence was too sparse and methodologically limited to support a stable comparative efficacy hierarchy among antidepressants."

Journal • Retrospective data • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Analysis of ocular adverse events associated with SNRIs. (PubMed, Front Pharmacol) - "This study aimed to investigate and compare the safety signals of ocular adverse events (AEs) associated with five major SNRIs (venlafaxine, duloxetine, desvenlafaxine, milnacipran, and levomilnacipran). Based on real-world data, this study identified drug-specific and sex-specific differences in the ocular safety signals of SNRIs. Mydriasis represents a common strong risk signal across multiple SNRIs."

Adverse events • Journal • CNS Disorders • Mental Retardation • Ophthalmology • Pain • Psychiatry

POST-MARKETING SAFETY PROFILE OF ANTIDEPRESSANTS IN 2013 TO 2025 (ISPOR 2026) - "Findings show numerous serious AE's associated with duloxetine, milnacipran, ketamine, and venlafaxine, which can lead to other serious outcomes, including hospitalization. It is necessary to continue and systematically monitor the safety associated with antidepressants and other associated medications."

Clinical • P4 data • CNS Disorders • Insomnia • Mood Disorders • Sleep Disorder

Examining individual serotonin and norepinephrine reuptake inhibitors and fall-related hospitalizations in older adults. (PubMed, Ment Health Clin) - "Data were drawn from Merative MarketScan Medicare Supplemental claims (January 1, 2015 to November 30, 2021), including adults 65 years and older prescribed an SNRI (ie, duloxetine, venlafaxine, desvenlafaxine, milnacipran, levomilnacipran). Venlafaxine appears to have a lower fall risk than duloxetine. Further studies are needed to determine clinical significance and assess fall-related costs to support safer SNRI use in older adults."

Journal • Geriatric Disorders

Disproportionality analysis of safety signals for milnacipran and levomilnacipran: a pharmacovigilance study using the FDA adverse event reporting system. (PubMed, Front Pharmacol) - "This real-world pharmacovigilance study has highlighted the distinct adverse event profiles of milnacipran and levomilnacipran, with a particular emphasis on sex-specific reactions. This differentiation supports the adoption of precision prescribing strategies and addresses the limitations often encountered in traditional clinical trial data."

Adverse events • Journal • Cardiovascular • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Pain • Psychiatry • Suicidal Ideation

Efficacy and Safety Study of Levomilnacipran Hydrochloride Extended-Release Capsules in Major Depressive Disorder (clinicaltrials.gov) - P3 | N=392 | Completed | Sponsor: Zhejiang Huahai Pharmaceutical Co., Ltd.

New P3 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis. (PubMed, Transl Psychiatry) - "Commonly used antidepressants have different gastrointestinal effects. Duloxetine, levomilnacipran, and vilazodone carry a higher risk of inducing nausea and vomiting, whereas trazodone, amitriptyline, agomelatine, and mirtazapine tend to be better tolerated. Amitriptyline, clomipramine, and reboxetine are more prone to induce constipation. Diarrhoea is more commonly associated with vilazodone, fluvoxamine, and sertraline. Amitriptyline, reboxetine, and duloxetine are more likely to cause anorexia. Amitriptyline, reboxetine, and trazodone are related to causing dry mouth. Compared with the placebo, amitriptyline, fluoxetine, and paroxetine were associated with a greater incidence of dyspepsia."

Journal • Retrospective data • Review • Anorexia • CNS Disorders • Constipation • Depression • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Major Depressive Disorder • Mood Disorders • Psychiatry • Xerostomia

Nickel-catalyzed highly diastereo- and enantioselective hydroaminocarbonylation and hydrocarboxylation of cyclopropenes. (PubMed, Nat Commun) - "These reactions feature mild reaction conditions, exceptional levels of enantioselectivities and diastereoselectivities while also exhibiting remarkable tolerance towards diverse functional groups. Moreover, our methodology proves to be highly efficient for the synthesis of pharmaceutical compounds such as Levomilnacipran and Bicifadine."

Journal

Real-World Cost-Effectiveness Analysis of Newer Antidepressants in Black Medicaid Beneficiaries: Evidence-Based Policy Reform to Address Treatment Disparities (ISPOR-EU 2025) - "Propensity score matching using demographics, comorbidities, baseline depression severity, and socioeconomic indicators compared outcomes between newer antidepressants (vortioxetine, vilazodone, levomilnacipran) versus standard generic options over 24-month follow-up. Real-world evidence demonstrating favorable cost-effectiveness of newer antidepressants enabled successful policy advocacy, resulting in modified prior authorization criteria across Maryland Medicaid managed care organizations. This approach provides a replicable framework for using HEOR evidence to address treatment disparities while achieving positive return on investment for healthcare stakeholders."

Clinical • Cost effectiveness • HEOR • Medicaid • Real-world • Real-world evidence • Reimbursement • US reimbursement • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Unveiling conformation-selective regulation of the norepinephrine transporter. (PubMed, Cell) - "Through cryo-electron microscopy analysis of NET complexes with levomilnacipran, vanoxerine, and vilazodone, we identify a previously undefined allosteric site within NET's inner vestibule that enables conformation-selective regulation. Moreover, our structural identification of inhibitor occupancy at this conformation-selective site defines a mechanistic framework for targeted therapeutic intervention. These findings advance our understanding of NET allosteric modulation, providing a structure-guided framework for developing next-generation antidepressants targeting the inward-open conformation of NET for the treatment of neuropsychiatric disorders."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Psychiatry

The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis. (PubMed, Lancet) - "We found strong evidence that antidepressants differ markedly in their physiological effects, particularly for cardiometabolic parameters. Treatment guidelines should be updated to reflect differences in physiological risk, but choice of antidepressant should be made on an individual basis, considering clinical presentation and preferences of patients, carers, and clinicians."

Journal • Retrospective data • CNS Disorders • Mental Retardation • Metabolic Disorders • Psychiatry

Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis. (PubMed, BMJ Open) - "The following antidepressants will be considered: agomelatine, alaproclate, bupropion, citalopram, desvenlafaxine, duloxetine, edivoxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine, vilazodone and vortioxetine. The findings will be published in a peer-reviewed journal and may be presented at international conferences. CRD420251011399."

Adverse events • Journal • Retrospective data • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • Suicidal Ideation

Beyond mood: a systematic review and network meta-analysis of the physiological and cardiometabolic effects of antidepressants (ECNP 2025) - "Clinically meaningful differences included approximately 4 kg variation in weight change, with significant weight loss observed for agomelatine and marked weight gain for maprotiline. Cardiovascular effects varied notably; nortriptyline increased heart rate by over 21 bpm relative to fluvoxamine, which decreased it...While paroxetine, duloxetine, desvenlafaxine, and venlafaxine decreased body weight, they significantly raised total cholesterol levels, with duloxetine additionally elevating glucose. Liver enzyme elevations were consistently observed with duloxetine, desvenlafaxine, and levomilnacipran, though these were not deemed clinically significant...Healthcare organisations recommend that consideration and discussion of potential side effects should form an integral part of the antidepressant prescribing process (3). Incorporating these differential physiological risks into clinical guidelines can support tailored prescribing decisions, balancing psychiatric..."

Retrospective data • Review • Bipolar Disorder • CNS Disorders • Depression • General Anxiety Disorder • Major Depressive Disorder • Mental Retardation • Mood Disorders • Musculoskeletal Pain • Obsessive-Compulsive Disorder • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia

Molecular mechanisms underlying cyclophosphamide-induced ovarian injury and protective strategies. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Quercetin, resveratrol, berberine, curcumin, irbesartan, mirtazapine, sildenafil, atorvastatin, donepezil, cilostazol, moxibustion, LCZ696, buspirone, levomilnacipran, melatonin, diosmin, and azilsartan are some of the agents that may protect against ovarian injury caused by CP, as shown in Graphical abstract. Our goal in writing this study is to provide a concise overview of the possible redox molecular pathways that cause ovarian harm in CP and how to potentially ameliorate them. Finally, investigation into these molecular pathways may pave the way for early ovarian damage relief and for the development of different agent strategies to alleviate CP-mediated POF."

Journal • Review • Inflammation • Oncology • Women's Health • IL6 • NLRP3 • TNFA

Optimization of Levomilnacipran Loaded Nanostructured Lipid Carrier Using Response Surface Methodology. (PubMed, Pharm Nanotechnol) - "This study demonstrated the effective application of RSM-CCRD for modelling LEVNLC."

Journal

Levomilnacipran, but Not Duloxetine, Inhibits Serotonin and Norepinephrine Reuptake Throughout Its Therapeutic Range. (PubMed, J Clin Psychiatry) - P4 | " Levomilnacipran is a potent dual reuptake inhibitor from its minimally effective dose in MDD, whereas the dose of duloxetine needs to reach 120 mg/day to consistently inhibit NE reuptake. Trial Registration: ClinicalTrials.gov identifier: NCT03249311."

Clinical • Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Factors associated with initial medication adherence with first-line therapy for depression. (PubMed, J Affect Disord) - "About 61 % of the MDD patients had optimal IMA with significant variation in IMA across antidepressant agents, in addition to other patients' characteristics. Findings highlight the importance of IMA and the need for targeted interventions to achieve optimal IMA."

Journal • Back Pain • Cardiovascular • CNS Disorders • Crohn's disease • Depression • Dermatology • Dyslipidemia • Gastroenterology • Genetic Disorders • Human Immunodeficiency Virus • Hypertension • Immunology • Infectious Disease • Inflammatory Arthritis • Inflammatory Bowel Disease • Major Depressive Disorder • Mood Disorders • Obesity • Psoriasis • Psoriatic Arthritis • Psychiatry • Rheumatology

CD9, a novel potential biomarker of sarcopenia. (PubMed, Sci Rep) - "Besides, dapoxetine, levomilnacipran, and milnacipran were predicted to target CD9 through molecular docking. Our study reported for the first time that CD9 is a novel potential biomarker of sarcopenia, and targeting CD9 may be a new idea for the development of therapeutic drugs for sarcopenia."

Biomarker • Journal • Musculoskeletal Diseases • Orthopedics • Sarcopenia • CD9

Gastrointestinal adverse events associated with SNRIs: A FAERS-based pharmacovigilance study. (PubMed, J Affect Disord) - "A retrospective analysis of FAERS data from 2004 to 2024 identified 114,148 reports involving five SNRI drugs (venlafaxine, desvenlafaxine, milnacipran, levomilnacipran, and duloxetine). Descriptive analyses revealed that middle-aged (45-64 years) and elderly (65-74 years) patients were more susceptible to gastrointestinal adverse events compared to younger age groups, although the specific effects varied across different drugs and age groups. These findings highlight the significant risks of gastrointestinal AEs associated with SNRIs, underscoring the need for individualized drug selection, close monitoring, and further research into underlying mechanisms and long-term impacts."

Adverse events • Journal • CNS Disorders • Constipation • Depression • Gastroenterology • Gastrointestinal Disorder • Major Depressive Disorder • Mood Disorders • Psychiatry • Xerostomia

Esketamine Combined With SSRI or SNRI for Treatment-Resistant Depression. (PubMed, JAMA Psychiatry) - "Treatment with esketamine combined with an SSRI (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, or vilazodone) or an SNRI (desvenlafaxine, duloxetine, levomilnacipran, milnacipran, or venlafaxine). In this retrospective comparative effectiveness study, among the study sample, incidence of mortality, hospitalizations, depressive relapses, and suicide attempts was low. The esketamine + SNRI group showed lower incidence of mortality, hospitalizations, and depressive relapses, while the esketamine + SSRI group showed a slightly lower incidence of suicidal attempts."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Repurposing levomilnacipran to attenuate premature ovarian insufficiency induced by cyclophosphamide in female Wistar albino rats through modulation of TLR4/p38-MAPK/NF-κB p65, Caspase-3-driven apoptosis, and Klotho protein expression. (PubMed, Food Chem Toxicol) - "LVM mitigated POI caused by CPA by downregulating TLR4/p38 MAPK/NF-κB p65, enhancing the α-Klotho level and attenuating caspase-3 derived apoptosis."

IO biomarker • Journal • Preclinical • Women's Health • BAX • BCL2 • CASP3 • IL18 • IL1B • KL • NFKB1 • RELA • TLR4 • TNFA

Levomilnacipran alleviates cyclophosphamide-induced hepatic dysfunction in male Wistar albino rats; emerging role of α-Klotho/TLR4/p38-MAPK/NF-κB p65 and caspase-3-driven apoptosis trajectories. (PubMed, Int Immunopharmacol) - "LVM alleviated hepatic injury generated by CPA via downregulating TLR4/p38 MAPK/NF-κB p65 signaling cascade through the participation of α-Klotho, as well as inhibiting caspase-3-driven apoptosis."

Journal • Preclinical • Hepatology • Liver Failure • CASP3 • IL18 • IL1B • MYD88 • RELA • TLR4 • TNFA

Reconsidering OCD pharmacotherapy: The case for levomilnacipran as a safer alternative to clomipramine. (PubMed, Pharmacol Biochem Behav) - No abstract available

Journal • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Evaluation of inhibitory actions of antidepressants on muscarinic receptors assessed by a binding assay in the mouse cerebral neocortex. (PubMed, J Pharmacol Sci) - "Of those tested, nine antidepressants (10-4 M) exhibited less inhibitory effect on [3H]NMS-specific binding (<35%): tianeptine (a tricyclic); trazodone (a serotonin 5-HT2A blocker); sulpiride (a dopamine D2 blocker); fluvoxamine (a selective serotonin reuptake inhibitor (RI)); milnacipran, levomilnacipran, venlafaxine, and desvenlafaxine (serotonin and noradrenaline RIs); and bupropion (a noradrenaline and dopamine RI). Therefore, these antidepressants show little anticholinergic effect in the brain and are recommended for use in patients with AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders

Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis. (PubMed, Andrology) - "For patients undergoing SAEs following the administration of antidepressants, trazodone, vortioxetine, vilazodone and agomelatine are alternative antidepressants."

Journal • Retrospective data • Review • CNS Disorders • Depression • Erectile Dysfunction • Major Depressive Disorder • Mood Disorders • Psychiatry