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

High-performance liquid chromatography-tandem mass spectrometry for simultaneous determination of 23 antidepressants and active metabolites in human serum and its application in therapeutic drug monitoring. (PubMed, Front Pharmacol) - "In this paper, we developed a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to study simultaneously TDM and clinical pharmacokinetics of 23 antidepressants and active metabolites: sertraline, escitalopram, fluvoxamine, paroxetine, duloxetine, milnacipran, fluoxetine, venlafaxine, O-desmethylvenlafaxine, mirtazapine, trazodone, bupropion, hydroxybupropione, norfluoxetine, vortioxetine, agomelatine, mianserin, doxepine, desmethyldoxepin, clomipramine, desmethylclomipramine, amitriptyline and nortriptyline hydrochloride...Validation of the developed method was carried out based on the Chinese Pharmacopoeia guidelines for bioanalytical method validation, including assessment of specificity, calibration curves, carryover, accuracy, crosstalk, precision, stability, recovery, dilution integrity and matrix effect. The results showed that a simple, fast, reliable and specific HPLC'MS/MS method was developed and validated, and all the..."

Journal • CNS Disorders • Depression • Psychiatry

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

Comparison of Selective Serotonin Reuptake Inhibitors and USA Food and Drug Administration-Approved Serotonin-Norepinephrine Reuptake Inhibitors Treatments for Fibromyalgia: A Systematic Review and Network Meta-Analysis (ISPOR 2025) - "The NMA supports the therapeutic effectiveness of paroxetine, duloxetine, and milnacipran for fibromyalgia. Paroxetine, although used off-label, showed promise in improving sleep and pain. Treatment decisions should consider individual patient preferences and symptom profiles."

Retrospective data • Review • CNS Disorders • Cognitive Disorders • Depression • Fatigue • Fibromyalgia • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology

Treatments for enhancing sleep quality in fibromyalgia: a systematic review and meta-analysis. (PubMed, Rheumatology (Oxford)) - "CBT-I is a promising treatment for enhancing sleep quality in fibromyalgia. Pharmacological treatments like pregabalin may be beneficial but should be used cautiously due to potential risks. Future research should prioritise trials focusing on sleep as a primary outcome and explore the comparative effectiveness of pharmacological treatments and CBT-I in fibromyalgia. Understanding the mechanisms linking sleep and fibromyalgia will also help guide future therapies."

Journal • Retrospective data • CNS Disorders • Fibromyalgia • Insomnia • Musculoskeletal Pain • Pain • Rheumatology • Sleep Disorder

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) for Treatment of Fibromyalgia: A Comprehensive Clinical Review. (PubMed, Psychopharmacol Bull) - "Currently, duloxetine and milnacipran are approved by the Food and Drug Administration although other agents in this drug class including venlafaxine and desvenlafaxine have been studied in the management of fibromyalgia. In addition, selective norepinephrine reuptake inhibitors, esreboxetine and reboxetine, as well as tramadol, a weak opioid mu-receptor agonist with SNRI activity have shown potential utility...Further information is needed to optimize patient selection and dosing regimens as well as elucidate the clinical factors associated with poor response. Moreover, pharmacologic agents may be combined with lifestyle changes and non-drug-based treatments to address the complex interactions of biological and psychosocial factors that facilitate disease development and persistence of symptoms."

Journal • Review • CNS Disorders • Fatigue • Fibromyalgia • Musculoskeletal Diseases • Musculoskeletal Pain • Neuralgia • Pain • Rheumatology

Milnacipran and Vanillin Alleviate Fibromyalgia-Associated Depression in Reserpine-Induced Rat Model: Role of Wnt/β-Catenin Signaling. (PubMed, Mol Neurobiol) - "Fibromyalgia (FM) patients are highly susceptible to depression. Interestingly, these effects of Miln and Van were overturned via administration of the β-catenin inhibitor, XAV939 (0.1 mg/kg, i.p., daily). In conclusion, this study outlined the antidepressant aptitude of Miln and Van through activating Wnt/β-catenin signaling in the hippocampus in reserpine-induced FM."

Journal • Preclinical • CNS Disorders • Depression • Fibromyalgia • Mood Disorders • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology

Innovative role of the antidepressant imipramine in esophageal squamous cell carcinoma treatment: Promoting apoptosis and protective autophagy. (PubMed, Int Immunopharmacol) - "Our findings provide the first reported evidence that IM triggers apoptosis and protective autophagy in ESCC cells via the Hippo signaling pathway, thus suggesting that IM may offer a promising therapeutic approach for patients with ESCC and depression."

Journal • CNS Disorders • Depression • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Psychiatry • Solid Tumor • Squamous Cell Carcinoma • ANXA5 • CASP3

Effect of Foot Massage Performed to the Mother After Bırth on Breastfeedıng Success, Sleep Qualıty and Newborn Stress (clinicaltrials.gov) - P=N/A | N=70 | Active, not recruiting | Sponsor: Melek Nur KEÇELİ

New trial

PHARMACOLOGICAL OPTIONS FOR MANAGING BURNING MOUTH SYNDROME. (WRMC 2025) - "Other medications evaluated included: amisulpride, aripiprazole, bupivacaine, cannabis, duloxetine, gabapentin, lysozyme-lactoperoxidase, melatonin, milnacipran, naltrexone, olanzapine, palmitoylethanlamide, paroxetine, pramipexole, pregabalin, sertraline, tibolone, and vortioxetine...Conclusions Although few studies have evaluated the use of pharmacological agents in the management of BMS, several have demonstrated efficacy including ALA, clonazepam, and capsaicin. Providers may refer to this review when managing patients with BMS. Drug Mechanism of Actions and Adverse Effects"

Dyspepsia • Pain

Impact of different treatments for chronic pain on cognitive function: A systematic review. (PubMed, Br J Pain) - "The strategies of intervention/treatment and durations varied widely; however, milnacipran versus placebo emerged as the most frequently employed intervention...Based on this analysis, it is not possible to affirm that interventions targeting chronic pain improve cognition. This review suggests new research directions and calls for more robust methodological approaches."

Journal • Back Pain • Fibromyalgia • Lumbar Back Pain • Musculoskeletal Pain • Pain • Rheumatology

SPR: The Savella Pregnancy Registry (clinicaltrials.gov) - P=N/A | N=350 | Terminated | Sponsor: Syneos Health | Trial completion date: Jun 2025 ➔ Oct 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ Oct 2024; Per the FDA, there is no regulatory requirement to continue this registry.

Trial completion date • Trial primary completion date • Trial termination • Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology

Effectiveness of pharmacological therapies for fibromyalgia syndrome in adults: an overview of Cochrane Reviews. (PubMed, Rheumatology (Oxford)) - "Duloxetine, milnacipran, and pregabalin had good evidence that about 1 person in 10 with moderate or severe pain experienced pain intensity reduction by at least 50%."

Journal • CNS Disorders • Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology

Effectiveness of pharmacological therapies for fibromyalgia syndrome in adults: an overview of Cochrane Reviews. (PubMed, Rheumatology (Oxford)) - "Duloxetine, milnacipran, and pregabalin had good evidence that about 1 person in 10 with moderate or severe pain experienced pain intensity reduction by at least 50%."

Journal • CNS Disorders • Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology

Short-Term Risk of Type 2 Diabetes in Patients Using Various Antidepressants Compared with Patients Using Fluoxetine. (PubMed, Psychiatry Clin Psychopharmacol) - "The HRs (95% confidence intervals) for T2D incidence in the various AD groups compared with that in the fluoxetine group are as follows: 0.84 (0.67-1.06, P = .15), bupropion; 0.91 (0.77- 1.07, P=.25), tianeptine; 0.91 (0.77-1.07, P=.25), escitalopram; 0.96 (0.82-1.13, P = .63), paroxetine; 0.97 (0.70-1.35, P=.87), fluvoxamine; 1.07 (0.85-1.36, P=.55), vortioxetine; 1.07 (0.91-1.25, P=.42), sertraline; 1.14 (0.99-1.31, P = .07), duloxetine; 1.17 (0.97-1.41, P = .09), mirtazapine; 1.17 (1.00-1.38, P=.05), trazodone; 1.22 (1.04-1.45, P=.02), venlafaxine; and 1.29 (1.03-1.61, P = .03), milnacipran. All other ADs except milnacipran and venlafaxine showed no difference in the risk of developing T2D compared to fluoxetine. These results suggest that clinicians should be mindful of the risk of developing T2D when administering milnacipran and venlafaxine to patients."

Journal • CNS Disorders • Depression • Diabetes • Metabolic Disorders • Mood Disorders • Psychiatry • Type 2 Diabetes Mellitus

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

Antidepressants for pain management in adults with chronic pain: a network meta-analysis. (PubMed, Health Technol Assess) - "Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that for duloxetine...62. See the NIHR Funding and Awards website for further award information."

Clinical • Journal • Retrospective data • Review • CNS Disorders • Depression • Fibromyalgia • Musculoskeletal Diseases • Musculoskeletal Pain • Neuralgia • Pain • Psychiatry • Rheumatology

Fibromyalgia Diagnosis and Treatment Receipt in the U.S. Military Health System. (PubMed, Mil Med) - "Overall, service members diagnosed with fibromyalgia received variable guideline-congruent health care within the 3 months before and after fibromyalgia diagnosis. Almost 1 in 3 service members received an opioid prescription, which has been explicitly recommended against use in guidelines. Pairwise comparisons indicated unwarranted variation across assigned sex and race and ethnicity in both co-occurring health conditions and care receipt. Underlying reasons for health and health care inequities can be multisourced and modifiable. It is unclear whether the U.S. Military Health System has consolidated patient resources to support patients living with fibromyalgia and if so, the extent to which such resources are accessible and known to patients and their clinicians."

Journal • CNS Disorders • Fibromyalgia • Gynecology • Insomnia • Mental Retardation • Migraine • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology • Sleep Disorder

TRPA1 Participates in Reserpine-induced Painful and Comorbid Symptoms in an Experimental Fibromyalgi (IASP 2024) - "Pharmacological therapy for symptom relief consists of pregabalin, duloxetine, or milnacipran use2...A967079, a TRPA1 antagonist, reversed the reserpine-induced pain, fatigue, anxiety, and depressive-like symptoms... The current study confirms the involvement of channel TRPA1 on the pain and comorbid symptoms induced by reserpine in a reserpine-induced fibromyalgia model in mice. The TRPA1 antagonist showed improved effects on fibromyalgia symptoms than drugs currently used to treat fibromyalgia. The use of knockout animals reinforces the TRPA1 role in this condition."

CNS Disorders • Depression • Fatigue • Fibromyalgia • Migraine • Mood Disorders • Musculoskeletal Pain • Pain • Psychiatry • Rheumatology • TRPA1

Management of Fibromyalgia: An Update. (PubMed, Biomedicines) - "Treatment emphasizes a comprehensive approach, combining nonpharmacological interventions such as aforementioned education, exercise, and psychotherapy, alongside pharmacologic management-namely duloxetine, milnacipran, pregabalin, and amitriptyline-which have consistent benefits for a range of symptoms across the spectrum of fibromyalgia. Notably, drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are generally not recommended due to limited efficacy and associated risks. Lastly, a variety of other medications have shown promise, including NMDA-receptor antagonists, naltrexone, and cannabinoids; however, they should be used with caution due to a small amount of evidence and potential for adverse effects."

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

Ten years of maintenance treatment of severe melancholic depression in an adult woman including discontinuation experiences. (PubMed, Fortschr Neurol Psychiatr) - "In this case, high-dose venlafaxine has a particular relapse-preventive (and "recurrence-preventive") effect with good long-term tolerability."

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

Adverse event profiles of drug-induced liver injury caused by antidepressant drugs: a disproportionality analysis. (PubMed, Ther Adv Drug Saf) - "Among the identified 42 antidepressants, nefazodone (n = 47, ROR = 7.79, IC = 2.91), fluvoxamine (n = 29, ROR = 4.69, IC = 2.20), and clomipramine (n = 24, ROR = 3.97, IC = 1.96) had the highest ROR for cholestatic injury; mianserin (n = 3, ROR = 21.46, IC = 3.99), nefazodone (n = 264, ROR = 18.67, IC = 3.84), and maprotiline (n = 15, ROR = 5.65, IC = 2.39) for hepatocellular injury; and nefazodone (n = 187, ROR = 12.71, IC = 0.48), clomipramine (n = 35, ROR = 2.07, IC = 0.26), and mirtazapine (n = 483, ROR = 1.96, IC = 0.94) for severe drug-related hepatic disorders...There are limited reports on the adverse reactions of relatively new antidepressant drugs, such as milnacipran, viloxazine, esketamine, and tianeptine, and those not approved by the Food and Drugs Administration, such as reboxetine and agomelatine...Duloxetine and clomipramine were associated with three DILI categories, except hepatic failure. The disproportionality analysis cannot conclude on a definite..."

Adverse events • Journal • CNS Disorders • Depression • Hepatology • Liver Failure • Mental Retardation • Psychiatry

Low dose Naltrexone, any unexplored role in managing excoriation disorder? (APA 2024) - "Her medication regimen included Gabapentin 1200 mg PO TID. She had previously undergone various medication trials to manage her fibromyalgia, depression, and ED, including Pregabalin, Duloxetine, Milnacipran, Amitriptyline, Venlafaxine, Sertraline, Fluoxetine, etc., without experiencing significant benefits...Conclusions : The effectiveness of LDN in our case suggests its potential role in managing excoriation disorder, possibly due to its immunomodulatory and anti-inflammatory effects. Due to its overall better safety profile, including fewer drug-drug interactions and improved tolerance, we believe that LDN might play a significant, yet unexplored, role in treating ED."

CNS Disorders • Depression • Dermatology • Fibromyalgia • Fibrosis • Immunology • Lichen Planus • Musculoskeletal Pain • Obsessive-Compulsive Disorder • Pain • Pruritus • Psoriasis • Psychiatry • Psychosomatic Disorders • Rheumatology • Scleroderma • Systemic Sclerosis

Pharmacological Treatments for Localized Provoked Vulvodynia: A Scoping Review. (PubMed, Int J Sex Health) - "Oral gabapentin and oral desipramine showed some improvement in sexual function compared to placebo...Pain was reduced in descriptive studies of tricyclic antidepressants, milnacipran, injectable anesthetics, and botulinum toxin...The breadth of therapies for treating LPV warrants the development of evidence-based, consensus guidelines for measuring treatment outcomes and improving comparisons across studies. Recommendations for research include addressing methodological shortcomings and diversifying the participant pool to increase the generalizability of findings."

Journal • Review • Anesthesia • Neuralgia • Pain • Women's Health

Identification of Potentially Repurposable Drugs for Lewy Body Dementia Using a Network-Based Approach. (PubMed, J Mol Neurosci) - "We found that most of the 154 FDA-approved drugs predicted by SAveRUNNER were used to treat nervous system disorders, but some off-label drugs like quinapril and selegiline were interestingly used to treat hypertension and Parkinson's disease (PD), respectively. These potential anti-LBD drugs are either selective or non-selective inhibitors of serotonin, dopamine, and norepinephrine transporters. The validated selective serotonin and norepinephrine inhibitors like milnacipran, protriptyline, and venlafaxine are predicted to manage LBD along with the affecting symptomatic issues."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Hypertension • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry • Sleep Disorder

"Fibromyalgia - are there any new approaches?". (PubMed, Best Pract Res Clin Rheumatol) - "The combination of therapies, whether old, recent or reformulated, are the most effective strategy for managing symptoms in patients with fibromyalgia."

Journal • Review • Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology