reboxetine / Generic mfg. - LARVOL DELTA

ECHINATIN AS A MULTIMODAL MODULATOR OF MONOAMINERGIC SYSTEM: PRECLINICAL EVIDENCE FOR ANTIDEPRESSANT-LIKE ACTIVITY. (PubMed, Eur J Pharmacol) - "Male BALB/c mice received echinatin (20 or 30 mg/kg), fluoxetine (10 mg/kg) or reboxetine (20 mg/kg). The anti-immobility effect was abolished by serotonergic (PCPA, WAY-100635), noradrenergic (AMPT, phentolamine, propranolol) and dopaminergic (SCH-23390, sulpiride) interventions, but was not altered by ketanserin. These findings provide the first pharmacological evidence that echinatin elicits antidepressant-like effects through broad monoaminergic modulation and support its further evaluation as a potential lead compound for antidepressant drug development."

Journal • Preclinical • CNS Disorders • Mood Disorders • Psychiatry

Necl1 deficiency induces noradrenergic dysfunction and depressive-like states in rodents: A cross-species model validated by pharmacological intervention. (PubMed, J Affect Disord) - "Our study establishes Necl1 as a synaptic-noradrenergic integrator that gates emotional processing via region-specific circuits. The Necl1 knockout rat serves as a stable genetic model of depression, while the knockout mouse presents a valuable model for studying anxiety-related mechanisms, together providing a cross-species platform for investigating emotional regulation."

Journal • Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • 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

Neurocompuational Underpinning of Valuation Uncertainty in Healthy Humans (Neuroscience 2025) - "We tested how reboxetine (NE enhancer), methylphenidate (DA enhancer), and nicotine (ACh enhancer) affect valuation uncertainty. Both DA and NE decreased perceived valuation uncertainty and attenuated the extent to which noise scaled with outcome magnitude. Additionally, DA lowered the conservative decision criterion, becoming more certain overall across noise conditions, while NE reduced both prior noise and encoding noise in value representation."

Clinical • CNS Disorders

Efficacy of adjunctive antidepressants in treating negative symptoms of schizophrenia: a systematic review and network meta-analysis. (PubMed, Psychol Med) - "These findings suggest that adjunctive use of mirtazapine and duloxetine can effectively improve the negative symptoms of schizophrenia in patients who are stably receiving antipsychotic treatment. Therefore, incorporating antidepressants into future treatment plans for negative symptoms of schizophrenia is a promising strategy that warrants further exploration."

Clinical • Journal • Retrospective data • Review • CNS Disorders • Psychiatry • Schizophrenia

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

Redressing long-term antidepressant use in general practice (RELEASE) (ECNP 2025) - "Antidepressants include selective serotonin reuptake inhibitors (sertraline, escitalopram fluoxetine, paroxetine, fluvoxamine and citalopram); serotonin and norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine, duloxetine); and other antidepressants (mirtazapine, vortioxetine, mianserin, moclobemide, reboxetine, agomelatine). 26 practices and 485 participants randomised. Data collection complete November 2025. Implications: This study will develop new knowledge applicable internationally on the effectiveness, cost-effectiveness, and implementation of the RELEASE multi-strategy intervention in prompting review of antidepressant medication and supporting informed decision-making and safe cessation via hyperbolic tapering to minimise withdrawal symptoms to improve primary mental health care and outcomes for patients."

Alzheimer's Disease • CNS Disorders • Dementia • Mood Disorders • Neuralgia • Psychiatry

Noradrenergic modulation of appetite and impulse control: reboxetine in a treatment-resistant case of bulimia nervosa (ECNP 2025) - "The initial treatment comprised fluoxetine 20 mg/day (increased up to 60 mg/day in the follow-up of one month) and the add-on of aripiprazole 5 mg/day, in conjunction with dietary interventions...Fluoxetine was gradually reduced, and sertraline 50 mg/day was initiated and titrated up to 200 mg/day within a month...Its noradrenergic effect may assist in diminishing binge eating and associated symptoms. Additional studies, particularly randomized controlled trials, are necessary to elucidate its function in the pharmacological treatment of eating disorders."

Clinical • Bulimia • CNS Disorders • Mental Retardation • Psychiatry

A network meta-analysis of Noradrenergic-Antimuscarinic Combinations for Obstructive Sleep Apnea (ERS 2025) - "Compared to placebo, 4mg reboxetine + 20mg hyoscine butylbromide best reduced apnea-hypopnea index (AHI)3% (surface under cumulative ranking curves [SUCRAs] 80%; mean difference [MD] = -18; 95% confidence interval [CI] -45.67, -9.76). Most regimens didn't affect NREM (non-rapid eye movement) or total sleep time but reduced REM sleep time compared to placebo. Conclusion With the equivalence of the interventions in reducing AHI and affecting sleep architecture, reboxetine 4mg + oxybutynin 5mg shows the most promise in managing OSA by significantly reducing hypoxic burden versus other interventions."

Retrospective data • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

INTEGRATIVE SYSTEMATIC REVIEW ON PHARMACOLOGICAL, PSYCHOTHERAPEUTIC AND NEUROSTIMULATORY TREATMENT OPTIONS IN TREATMENT-RESISTANT ANXIETY DISORDERS. (PubMed, Psychother Psychosom) - "According to RCTs, selective serotonin reuptake inhibitors (SSRI) or clomipramine are effective in TR-PD after failure to respond to cognitive behavioral therapy (CBT). In pharmacological TR-SAD, switching from one SSRI to another or to venlafaxine was found helpful in open label trials. RCTs further suggest augmentation with quetiapine, risperidone, olanzapine or pregabalin in TR-GAD, pindolol in TR-PD and clonazepam in TR-SAD. Open label studies in TR-AD provide preliminary evidence for ketamine or augmentation with nefazodone, reboxetine, buspirone, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, divalproex sodium, levetiracetam, zonisamide, flumazenil, pregabalin, cannabidiol and acamprosate...Only inconclusive support was identified for repetitive transcranial magnetic stimulation (rTMS) in TR-AD. In summary, this integrative review may provide an evidence base for expert recommendations, inform clinical guidelines, and inspire further research into..."

Journal • Review • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry • Social Anxiety Disorder

Effects of Reboxetine alone and in combination with Oxybutynin on quantitative electroencephalogram measures of alertness in obstructive sleep apnea (WSS 2025) - "Reboxetine with and without oxybutynin did not improve or impair morning alertness as measured by delta and theta EEG power during resting wakefulness. Despite the lack of improved alertness, these findings support the safety profile of these agents."

Combination therapy • CNS Disorders • Excessive Daytime Sleepiness • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder

An Updated Network Meta-Analysis of Pharmacological Therapies for Obstructive Sleep Apnea: Effects on AHI Reduction and Lowest Oxygen Saturation Improvement (WSS 2025) - "For AHI reduction, 80 mg atomoxetine combined with 5 mg oxybutynin demonstrated the most pronounced effect (MD –17.03 events/hour; 95% CI –23.63 to –10.43), followed by 80 mg atomoxetine plus 50 mg trazodone (MD –14.40; 95% CI –24.94 to –3.86) and 100 mg trazodone monotherapy (MD –13.70; 95% CI –22.19 to –5.21). Selected pharmacologic treatments, particularly atomoxetine-based combinations, significantly reduced AHI, while reboxetine improved SpO₂ nadir. These agents may offer alternative options for patients intolerant to CPAP, though further studies are needed to confirm their efficacy and safety."

Retrospective data • CNS Disorders • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

5-HT as a Diagnostic Tool on the Continuum between Temperament and Disease (WFSBP 2025) - " In a sample of 36 healthy males divided according to an anhedonia questionnaire (Chapman, 1972) into high versus low physical and social anhedonia respectively, specific noradrenergic, dopaminergic and serotonergic psychopharmacological drugs (reboxetine, bromocriptine and citalopram respectively ) were administered in a balanced crossover design at one week intervals. These findings very much resemble the patterns observed in respective psychiatric patients characterised by anhedonia : Low dopamine is evidently related to the overall lack of initiative and motivation in anhedonia, but, specifically low responses to the 5-HT challenge indicate the close relationship between lack of social responsiveness in the normal range and in psychopathy. Results suggest that psychopharmacological challenges by transmitter- specific drugs may serve as diagnostic tools for discriminating subtypes of psychopathological symptoms, and that there is evidence for a continuum between..."

CNS Disorders • Depression • Psychiatry • Schizophrenia

Methylone promotes neurite outgrowth and has long-lasting effects on fear extinction learning. (PubMed, Neuropsychopharmacology) - "Methylone's effect on neurite branching was blocked by inhibitors of monoamine transporters (reboxetine, escitalopram, JHW-007) whereas its effects on the length of the longest neurite per cell were mediated by trkB receptors or mTor signaling. Reboxetine blocked methylone's improvement of extinction recall memory, suggesting NET activity is required for methylone's behavioral effect. Together, this work provides insight into methylone's mechanism of action and evidence that rapid-acting pharmacotherapies that induce structural neuroplasticity may have potential to treat PTSD."

Journal • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • NTRK2

Efficacy and Safety of Histamine H3 Receptor Antagonist/Inverse Agonist Including Betahistine for Schizophrenia: A Systematic Review and Meta-Analysis. (PubMed, Neuropsychopharmacol Rep) - "Some H3R-ANTs/H3R-IAs might provide benefit for the treatment of cognitive symptoms and depressive symptoms in individuals afflicted with schizophrenia."

Clinical • Journal • Retrospective data • Review • CNS Disorders • Insomnia • Psychiatry • Schizophrenia • Sleep Disorder

Comparative Efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) in the Management of Post-stroke Depression: A Systematic Review of Randomized Controlled Trials. (PubMed, Cureus) - "The findings revealed that both SSRIs and SNRIs significantly improved depressive symptoms, with escitalopram showing early and superior antidepressant effects compared to sertraline. SNRIs like duloxetine and reboxetine demonstrated added benefits in cognitive outcomes, prevention of PSD, and symptom subtype-specific efficacy, particularly in retarded depression. While the overall risk of bias was low in most studies, limitations such as small sample sizes and limited direct head-to-head comparisons were noted. These results support the clinical utility of both drug classes and emphasize the need for individualized pharmacologic strategies based on patient characteristics and symptom profiles."

Journal • Review • Cardiovascular • CNS Disorders • Depression • Mood Disorders • Psychiatry

The Role of the Brain in Mental and Physical Fatigue (clinicaltrials.gov) - P3 | N=62 | Recruiting | Sponsor: Vrije Universiteit Brussel | Trial completion date: Mar 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • CNS Disorders • Fatigue

Did Serendipity Contribute to the Discovery of New Antidepressant Drugs? Historical Analysis Using Operational Criteria. (PubMed, Alpha Psychiatry) - "Selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine, citalopram, paroxetine, sertraline, and escitalopram), selective dopamine and noradrenaline reuptake inhibitors (bupropion), noradrenaline and serotonin reuptake inhibitors (venlafaxine, milnacipram, duloxetine, and desvenlafaxine), selective noradrenaline reuptake inhibitors (reboxetine), noradrenergic and specific serotonergic antidepressants (mirtazapine), melatonergic agonists (agomelatine), and serotonin modulators and stimulators (vortioxetine, vilazodone, tianeptine) correspond to the type IV pattern. Ketamine, a glutamatergic modulator, corresponds to the type III pattern, characterized by a non-serendipitous origin (initial development as an anesthetic agent) leading to a serendipitous observation (the discovery of antidepressant efficacy in individuals illicitly using). The majority of new antidepressants adhere to a type IV pattern, characterized by a rational and targeted design process where..."

Journal • Anesthesia

Neuron-astrocyte coupling in lateral habenula mediates depressive-like behaviors. (PubMed, Cell) - "These results identify a stress-induced positive feedback loop in the LHb-LC axis, with astrocytes being a critical signaling relay. The identification of this prominent neuron-glia interaction may shed light on stress management and depression prevention."

Journal • CNS Disorders • Depression • Psychiatry

Efficacy of Reboxetine and Methylphenidate Treatment on Attentional, Sensory and Emotional Dysregulation in Adults With PTSD (clinicaltrials.gov) - P2 | N=53 | Recruiting | Sponsor: University of Haifa | Trial completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Nov 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Re-Evaluating Acceptable Intake: A Comparative Study of N-Nitrosomorpholine and N-Nitroso Reboxetine Potency. (PubMed, Environ Mol Mutagen) - "The data presented in this work can be used to refine and improve the Carcinogenic Potency Categorization Approach (CPCA). It also underscores the importance of collaboration between regulatory authorities, the pharmaceutical industry, and scientific researchers to address potential risks while avoiding overestimation of the acceptable intake limits for certain NDSRIs."

Journal

Uncovering the Elusive Structures and Mechanisms of Prevalent Antidepressants. (PubMed, Adv Ther (Weinh)) - "In this study, we apply microcrystal electron diffraction (MicroED) to reveal the atomic 3D structures for the first time of five of the most prevalent antidepressants (reboxetine, pipofezine, ansofaxine, phenelzine, bifemelane) directly from the commercially available powder of the active ingredients. Their modes of binding are investigated by molecular docking, revealing the essential contacts and conformational changes into the biologically active state. This study underscores the combined use of MicroED and molecular docking to uncover elusive drug structures and mechanisms to aid in further drug development pipelines."

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

A New Trick of Old Dogs: Can Kappa Opioid Receptor Antagonist Properties of Antidepressants Assist in Treating Treatment-Resistant Depression (TRD)? (PubMed, Pharmaceuticals (Basel)) - " The antidepressants mianserin and mirtazapine (separately) induced dose-dependent antinociception, each yielding a biphasic dose-response curve. Similarly, the antidepressant venlafaxine produced a potent effect and reboxetine produced a weak effect. The antipsychotics risperidone and amisulpride exhibited a dose-dependent antinociceptive effect... Clinical studies are mandatory to establish the potential efficacy of augmentation of the treatment with antidepressants with these drugs in persons with treatment-resistant depression and the optimal dosage of medications prescribed. We suggest a possible beneficial effect of antidepressants with kappa antagonistic properties."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

An Exploration of the Interplay Between Caffeine and Antidepressants Through the Lens of Pharmacokinetics and Pharmacodynamics. (PubMed, Eur J Drug Metab Pharmacokinet) - "The interaction between fluvoxamine and caffeine resulted in increased concentrations of caffeine in the body and lowered the renal clearance of fluvoxamine. Other SSRIs such as fluoxetine and escitalopram had augmented antidepressant effects by decreasing their renal clearance and prolonging their effects in the body when coadministered with caffeine. Caffeine may also increase the concentration of paroxetine, potentially affecting its pharmacodynamic effects. TCAs such as clomipramine, imipramine, desipramine, and sertraline, were found to reduce the metabolism of caffeine...The inhibition of caffeine at high doses when used with MAOIs such as tranylcypromine and phenelzine was found to lead to a higher likelihood of experiencing hypertension. Coadministration of caffeine with venlafaxine (SNRIs) suggests minimal interactions between the two substances and the pharmacodynamic effects of venlafaxine were unlikely to be impacted by caffeine consumption. Miscellaneous..."

Journal • PK/PD data • Review • Cardiovascular • CNS Disorders • Hypertension • Psychiatry

Identification of immune characteristics between different subtypes in kidney renal clear cell carcinoma based on lysosome-related genes to assist immunotherapy. (PubMed, Hum Immunol) - "Finally, based on the cMAP database, we identified some small molecules that may target DEGs between the two subtypes, such as epibatidine, mepyramine, and reboxetine. In conclusion, our investigation unearthed that different subtypes of KIRC patients exhibited different survival outcomes and sensitivity to the immune microenvironment, as well as different responses to immunotherapy. These findings may be beneficial for further mechanistic exploration and therapeutic research of KIRC in the future."

Biomarker • IO biomarker • Journal • Clear Cell Carcinoma • Clear Cell Renal Cell Carcinoma • Oncology • Renal Cell Carcinoma • Solid Tumor