Savella (milnacipran) / AbbVie, Pierre Fabre - LARVOL DELTA

Top 20 Research Studies of 2025 for Primary Care Physicians. (PubMed, Am Fam Physician) - "Women with normal bone density given zoledronic acid every 5 years have fewer fractures...For patients with provoked venous thromboembolism and at least one ongoing risk factor, 12 months of apixaban is better than 3 months. Clopidogrel is slightly more effective than aspirin for the secondary prevention of myocardial infarction and stroke over 3 years...Duloxetine, milnacipran, and pregabalin provide meaningful pain reduction in adults with fibromyalgia...A meta-analysis of platelet-rich plasma injections for knee osteoarthritis concluded that high-quality studies found no meaningful pain improvement. Using an oral challenge to rule out sulfonamide allergy is safe when used with a risk assessment tool."

Journal • Review • Allergy • Atherosclerosis • Atrial Fibrillation • Breast Cancer • Cardiovascular • CNS Disorders • Depression • Fibromyalgia • Hypotension • Immunology • Infectious Disease • Influenza • Long-acting Reversible Contraceptives • Musculoskeletal Diseases • Musculoskeletal Pain • Myocardial Infarction • Novel Coronavirus Disease • Oncology • Osteoarthritis • Pain • Psychiatry • Respiratory Diseases • Rheumatology • Solid Tumor • Vaginitis • Venous Thromboembolism

Chronopharmacology and implications for the safety and efficacy of anticonvulsants, antipsychotics, and antidepressants: A systematic review. (PubMed, J Psychopharmacol) - "Current evidence provides preliminary support that circadian rhythm may differentially affect the pharmacology of select psychotropic agents. Whether the foregoing translates into clinically meaningful differences in efficacy, tolerability, and/or posology of the evaluated agents/classes requires systematic evaluation. Given that evidence is predominantly preclinical, further studies using clinically relevant repeated-dose regimens and disease-relevant animal models are required."

Journal • Review • CNS Disorders • Epilepsy

Evolving Concepts in the Diagnosis and Management of Fibromyalgia: A Moving Target. (PubMed, J Pain Res) - "Pharmacological therapies, including pregabalin, duloxetine, milnacipran, and cyclobenzaprine, are Food and Drug Administration-approved and provide clinically meaningful benefits to patients with FM. Although tramadol may be considered, the use of other opioids is generally not recommended because of their limited efficacy and potential risks...Therefore, this narrative review aims to provide a concise, updated, and clinically relevant overview of the current evidence regarding the pathogenesis, diagnosis, and multidisciplinary management of FM to improve diagnostic accuracy and support individualized patient management. Furthermore, future directions should prioritize improving diagnostic precision and developing mechanism-based interventions targeting the underlying pathophysiology of FM."

Journal • Review • CNS Disorders • Cognitive Disorders • Fatigue • Fibromyalgia • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology • Sleep Disorder

A pharmacometric framework for norepinephrine transporter occupancy and dose equivalence across psychotropic medications. (PubMed, J Psychopharmacol) - "These findings suggest that variability in NET engagement across psychotropic medications may not be fully captured by conventional class-based classifications. The proposed framework offers a mechanism-informed approach to comparative pharmacological analysis and introduces a conceptual noradrenergic activity index. This approach may be useful for hypothesis generation in future studies integrating pharmacokinetic-pharmacodynamic modeling with in vivo imaging and clinical outcomes."

Journal

Drug-induced dysphagia: Analysis of age and time of onset profiles using a Japanese pharmacovigilance database. (PubMed, Int J Clin Pharmacol Ther) - "Drug-induced dysphagia profiles differ among drugs, particularly in terms of timing of onset and patient age distribution. Therefore, clinicians should consider both the causative drug and the patient's age when monitoring for dysphagia."

Adverse events • Journal • Gastrointestinal Disorder

Evaluating Caenorhabditis elegans as a Toxicity Model for Reuptake Inhibitors. (PubMed, MicroPubl Biol) - "Escitalopram showed greater toxicity than citalopram, duloxetine was more toxic than milnacipran, and desvenlafaxine, but not venlafaxine, produced toxicity. These results suggest that C. elegans cannot replace mammalian testing, but may serve as a rapid and low-cost prescreening model."

Journal

Physiologically Based Pharmacokinetic (PBPK) Modeling of Antidepressants: A Scoping Review of Existing Models, Applications, and Software Tools. (PubMed, Clin Pharmacokinet) - "Paroxetine, fluvoxamine, and venlafaxine were most frequently modeled (n = 10 each), whereas few or no models exist for substances such as mirtazapine (n = 1) or milnacipran (n = 0). Although physiologically based pharmacokinetic models for antidepressants are increasingly available, they focus on a limited number of drugs and applications. Substantial evidence gaps remain, particularly for vulnerable patient populations."

Journal • PK/PD data • Review • Geriatric Disorders • Pediatrics

Fibromyalgia - a complex construct with a multidisciplinary approach (CINP 2026) - "There are three drugs approved by FDA: pregabalin, duloxetine, and milnacipran. Duloxetine and milnacipran should be used in comorbid depression; Amitriptyline is recommended for sleep disturbances, while nortriptyline is better suited to treat fatigue. Antiepileptics (gabapentin, pregabalin) have been shown to modulate pain, promote physiological sleep, and act as an anxiolytic. Other pharmacologic options for treatment of pain include tramadol, low-dose naltrexone, and NMDA receptor antagonists. Armodafinil and methylphenidate improve fatigue and mood, and increase concentration; however, they require further clinical trials.Interestingly, the administration of placebo has proven more effective than no treatment in many clinical settings... Optimal management requires prompt diagnosis and providing the patient with information about the condition. There should be a comprehensive assessment of pain, function and the psychosocial context.It is recommended that..."

CNS Disorders • Cognitive Disorders • Depression • Fibromyalgia • Mood Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Rheumatology • Sleep Disorder

A clinical review of bupropion and pain (CINP 2026) - "While tricyclic antidepressants (TCAs) have been used historically off-label for neuropathic and fibromyalgia pain, the selective serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine and milnacipran, and pregabalin have formal indications for the latter.Bupropion is a norepinephrine and dopamine reuptake inhibitor (NDRI). This review of the literature coupled with our clinical experience suggests that bupropion may be an agent to consider in the management of neuropathic and fibromyalgia-related pain symptoms, particularly when accompanied by low energy and depressed mood."

Clinical • Review • CNS Disorders • Depression • Fibromyalgia • Major Depressive Disorder • Musculoskeletal Pain • Neuralgia • Pain • Sexual Disorders • Tobacco Cessation • TNFA

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

Milnacipran continuation during pregnancy in a patient with severe post-traumatic stress disorder and psychotic depression: a case report with 3-year pediatric follow-up. (PubMed, Front Psychiatry) - "After pregnancy confirmation, treatment was changed to sertraline plus quetiapine because of limited pregnancy safety data, but depressive symptoms and suicidal behavior reemerged within 2 weeks. At 3-year follow-up, pediatric developmental screenings remained within expected limits. This case illustrates the challenge of balancing relapse risk, prior treatment response, and treatment feasibility during pregnancy when evidence for the effective medication is limited."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Pediatrics • Post-traumatic Stress Disorder • Psychiatry • Rare Diseases

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

Serotonin-Norepinephrine Reuptake Inhibitors in Fibromyalgia Management: An Integrative Literature Review of Clinical Evidence. (PubMed, Clin Pract) - "Duloxetine showed superior efficacy for pain/depression; milnacipran excelled in sleep quality. Long-term studies and combination therapies warrant further investigation."

Clinical • Journal • Review • CNS Disorders • Depression • Fatigue • Fibromyalgia • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology

BDNF and Beyond: Unlocking the Therapeutic Potential of Neurotrophic Pathways in Depression (AAN 2026) - "Multimodal agents (e.g., vortioxetine) augmented glutamatergic transmission, LTP, and dendritic spine maturation; MAOIs elevated BDNF/IGF-1 and supported LTP. Rapid-acting NMDA antagonists (ketamine/esketamine) produced swift, durable antidepressant effects with increases in AMPA throughput, p-TrkB/c-CREB, and spine formation. Some drug classes showed heterogeneity (e.g., duloxetine/milnacipran with region-specific or inconsistent plasticity effects; sertraline with mixed LTP findings)...Targeting neurotrophic signaling (e.g., BDNF mimetics, IGF-1 analogs), pairing plasticity enhancers with standard antidepressants, and integrating neuromodulation may yield more durable remission and reduced relapse. Future work should standardize plasticity biomarkers (imaging, serum/csf neurotrophins) to stratify patients and optimize sequencing/combination of pharmacologic and device-based interventions."

CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • BDNF • IGF1

Efficacy and safety of Milnacipran hydrochloride tablets in the treatment of patients with depression (ChiCTR) - P4 | N=30 | Completed | Sponsor: Zhongda Hospital, Southeast University; Zhongda Hospital, Southeast University

New P4 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

When the Sella Looks Empty but the Diagnosis Isn’t: Isolated Corticotroph Dysfunction Unveiled (AACE 2026) - "Case Description A 50-year-old female with a medical history of fibromyalgia on milnacipran and rheumatoid arthritis on hydroxychloroquine and abatacept was evaluated for fatigue. Isolated ACTH deficiency in partial ES is an uncommon but important finding and highlights the need for careful endocrine evaluation. One possible explanation is subtle pituitary"

Fibromyalgia • Immunology • Inflammatory Arthritis • Musculoskeletal Pain • Rheumatoid Arthritis

Mind and Muscle: A Retrospective Study on the Management of Psychiatric Comorbidities in Patients With Fibromyalgia Treated With Pregabalin Versus Milnacipran. (PubMed, Cureus) - " Overall, differences observed between groups may not be clinically significant. This information may help clinicians and patients employ well-informed, shared decision-making."

Journal • Retrospective data • CNS Disorders • Depression • Fatigue • Fibromyalgia • Mood Disorders • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology • Substance Abuse

Depression following stroke and myocardial infarction: effective strategies and evidence gaps. A systematic review. (PubMed, Eur J Prev Cardiol) - "A holistic, multidisciplinary, and tailored approach encompassing pharmacological treatments together with non-pharmacological interventions (psychological therapy, device-based stimulation, and physical activity/exercise) is beneficial in reducing depression severity or risk amongst those with recent stroke, but there is a lack evidence for the long-term efficacy amongst those with recent MI."

Journal • Cardiovascular • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Myocardial Infarction • Psychiatry

Fibromyalgia Analog Model index analysis demonstrates the predictive validity of the Dahl S rat as a model of fibromyalgia. (PubMed, Pain) - "When compared to controls, treatments with the FDA-approved drugs for FMS milnacipran and pregabalin (both P < 0.0001, in males and females), as well as the investigational therapies metformin (P < 0.0001) and green light exposure (P = 0.0034 and P = 0.0002 for males and females, respectively) effectively decreased the FAM scores, showing reduction of FMS-like symptoms in SS rats. In contrast, indomethacin and the mu-opioid agonist DAMGO displayed limited efficacy (P = 0.0239 and P = 0.0523, respectively), matching the relative effectiveness of these treatments in humans, justifying why they are not usually prescribed for patients with FMS. The results validate the SS rat as a predictive model in testing pharmacologic and nonpharmacologic therapies for FMS treatment, illustrating the utility of the FAM index in assessing treatment outcomes."

Journal • Preclinical • CNS Disorders • Fatigue • Fibromyalgia • Mood Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology

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

Cost-Effectiveness of Pregabalin, Duloxetine, and Milnacipran vs Amitriptyline for Moderate to Severe Fibromyalgia. (PubMed, JAMA Netw Open) - "Amitriptyline provided greater net benefit than milnacipran and the lower doses of pregabalin and duloxetine. These findings may help inform the selection of value-based treatments for moderate to severe FM."

HEOR • Journal • Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology

Milnacipran for the treatment of refractory chronic cough: a report of two cases (PubMed, Zhonghua Jie He He Hu Xi Za Zhi) - "No recurrence was noted during an eight-week follow-up after drug withdrawal. These cases suggest that, in the absence of psychiatric disorders, milnacipran may effectively relieve cough symptoms in patients with RCC and could represent a promising therapeutic option for this condition."

Journal • Asthma • Chronic Cough • CNS Disorders • Cough • Gastroenterology • Gastroesophageal Reflux Disease • Immunology • Mental Retardation • Psychiatry • Pulmonary Disease • Renal Cell Carcinoma • Respiratory Diseases

Prediction of 12-Week Remission in Patients With Depressive Disorder Using Reasoning-Based Large Language Models: Model Development and Validation Study. (PubMed, JMIR Ment Health) - "We analyzed data from 390 patients in the MAKE Biomarker discovery study who were undergoing first-step antidepressant monotherapy with 12 different medications, including escitalopram, paroxetine, sertraline, duloxetine, venlafaxine, desvenlafaxine, milnacipran, mirtazapine, bupropion, vortioxetine, tianeptine, and trazodone, after excluding those with uncommon medications (n=9) or missing biomarker data (n=32). Clinical evaluation by psychiatrists showed favorable mean ratings for correctness (4.3, SD 0.7), consistency (4.2, SD 0.8), specificity (4.2, SD 0.7), helpfulness (4.2, SD 1.0), and human likeness (3.6, SD 1.7) on 5-point scales. These findings demonstrate that reasoning-based LLMs, particularly when enhanced with research-informed prompting, show promise for predicting antidepressant response and could serve as interpretable adjunctive tools in depressive disorder treatment planning, although prospective validation in real-world clinical settings remains..."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

From Years of Pain to a Name: Fibromyalgia Uncovered. (PubMed, Cureus) - "Effective pharmacologic options include duloxetine, milnacipran, pregabalin, and amitriptyline. However, after ruling out the common causes for diffuse chronic pain, fibromyalgia was diagnosed. This case illuminates the importance of clinicians being patient advocates throughout the journey and listening attentively to patients' concerns even when laboratory results and imaging appear unremarkable."

Journal • Bipolar Disorder • Cardiomyopathy • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Depression • Dermatology • Fatigue • Fibromyalgia • Gastrointestinal Disorder • Hidradenitis Suppurativa • Immunology • Major Depressive Disorder • Melanoma • Mood Disorders • Musculoskeletal Pain • Nephrology • Oncology • Pain • Post-traumatic Stress Disorder • Psychiatry • Renal Disease • Rheumatology • Solid Tumor

Sublingual cyclobenzaprine (Tonmya) for fibromyalgia. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology