modafinil / Generic mfg. - LARVOL DELTA

Histamine N-methyltransferase inhibition as a novel therapeutic strategy for idiopathic hypersomnia. (PubMed, Eur J Pharmacol) - "Although current treatments, including low-sodium oxybate and modafinil, are readily available for IH, they are associated with side effects such as drug dependence and abuse...Furthermore, the wake-up promoting effect of metoprine was more pronounced than that of other agents, including a histamine receptor H3 inverse agonist and an orexin receptor agonist. These findings suggest that the pharmacological inhibition of HNMT represents a promising therapeutic strategy for IH."

Journal • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Toward Practical and Sensitive Fluorescence Analysis: Factorial Design-Optimized o-Phthalaldehyde Derivatization for Synchronous Spectrofluorimetric Determination of Modafinil in Plasma and Dosage Form. (PubMed, Luminescence) - "MoGAPI, AGREE, and BAGI assessments yielded scores of 72, 0.62, and 70, respectively. The results show that the method is user-friendly and can be used in routine applications."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Fatigue

Assessing Condition-Specific Adverse Event Profiles of Modafinil for Labelled and Off-Label Uses: A Systematic Review and Meta-Analysis. (PubMed, Basic Clin Pharmacol Toxicol) - "While modafinil users share common AEs, specific risks vary across patient groups. Our findings on condition-specific AE profiles would support cautious prescribing of modafinil and careful consideration of alternative treatments."

Adverse events • Clinical • Journal • Retrospective data • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Depression • Excessive Daytime Sleepiness • Excessive Daytime Sleepiness in Narcolepsy • Insomnia • Major Depressive Disorder • Mood Disorders • Narcolepsy • Obstructive Sleep Apnea • Pain • Psychiatry • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Lessons Learned From a Delayed-Start Trial of Modafinil for Freezing of Gait in Parkinson's Disease. (PubMed, Ann Clin Transl Neurol) - "For future therapeutic trials, selecting PwPD with moderate, quantifiable FOG and utilizing appropriate outcome measures like %FT will improve the ability to identify intervention effects. Even for short trials, analyses must account for gait decline. An FOG outcome measure that requires less analysis time burden than video quantification, and the ability for at-home monitoring is needed."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

COSTEP 1: Cognitive Strategies in Early Psychosis 1 (clinicaltrials.gov) - P3 | N=103 | Recruiting | Sponsor: University of Minnesota | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry

Challenges of Treatment-Resistant Bipolar Depression in the Elderly: A Case Study of Successful Modafinil Augmentation. (PubMed, Cureus) - "Modafinil may be a safe and effective adjunct in treatment-resistant bipolar depression, especially when conventional therapies are contraindicated. Its use may extend beyond elderly populations to adults with similar clinical challenges."

Journal • Ataxia • Bipolar Disorder • Chronic Kidney Disease • CNS Disorders • Depression • Mood Disorders • Movement Disorders • Nephrology • Psychiatry • Renal Disease

COSTEP 2: Cognitive Strategies in Early Psychosis 2 (clinicaltrials.gov) - P3 | N=24 | Not yet recruiting | Sponsor: University of Minnesota

New P3 trial • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia • Schizophreniform Disorder

Efficacy of Fatigue Countermeasures on Cognitive Performance and Operational Safety in Military Pilots: A Systematic Review. (PubMed, Cureus) - "Pharmacological interventions, particularly caffeine and modafinil, were the most effective short-term countermeasures, improving vigilance, reaction time, and performance during extended wakefulness...Future fatigue management requires an integrated, personalized system combining real-time monitoring, validated countermeasures (including novel approaches and sleep-focused strategies), and a systemic cultural shift that prioritizes sleep as a critical component of operational readiness. Further high-fidelity research in real-world operational environments is essential."

Journal • Review • Fatigue

Modafinil-Induced Hyperkinetic Movements in Post-Stroke Patients: A Case Series. (PubMed, Mov Disord Clin Pract) - "Modafinil may rarely induce reversible hyperkinetic movements in elderly stroke patients. Clinicians should monitor for abnormal movements during its use, particularly in neurologically vulnerable individuals."

Journal • Cardiovascular • Movement Disorders

Modafinil for Promoting Wakefulness in Critically Ill Patients: Current Evidence and Perspectives. (PubMed, Clocks Sleep) - "Nonetheless, robust conclusions regarding efficacy and safety remain limited by the small sample sizes and methodological constraints of the available studies. Consequently, further large-scale RCTs are warranted to elucidate the therapeutic role of modafinil in the management of EDS and hypoactivity among ICU patients."

Journal • Review • Cardiovascular • CNS Disorders • Cognitive Disorders • Critical care • Excessive Daytime Sleepiness • Fatigue • Sleep Disorder • Vascular Neurology

The incidence, prevalence and treatment of narcolepsy in New Zealand. (PubMed, N Z Med J) - "This is the first national estimate of the incidence and prevalence of narcolepsy in New Zealand. The mismatch between diagnosis and treatment data likely reflects limited diagnostic access, multiple medication use, the existence of imported cases with established diagnoses and the treatment of idiopathic hypersomnolence (IH) under the guise of narcolepsy. Policy and funding changes are needed to improve care access and reporting accuracy."

Journal • Narcolepsy • Sleep Disorder

Use of Symptomatic Drug Treatment for Fatigue in Multiple Sclerosis and Patterns of Work Loss. (PubMed, Ann Clin Transl Neurol) - "A potential minor treatment benefit is suggested by the statistically significant, small attenuation of worsening work loss following fatigue treatment initiation compared with untreated people with MS. No differences in treatment benefit were observed across fatigue treatments."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Fatigue • Multiple Sclerosis • Psychiatry

COSTEP 1: Cognitive Strategies in Early Psychosis 1 (clinicaltrials.gov) - P3 | N=103 | Not yet recruiting | Sponsor: University of Minnesota

New P3 trial • CNS Disorders • Psychiatry

A Case of Decompensated Cirrhosis Secondary to Sickle Cell Hepatopathy (SCH) Managed With Orthotopic Liver Transplantation (OLT) Followed by Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) (ACG 2025) - "Despite treatment of SCD with transfusions and hydroxyurea, his cirrhosis progressed with refractory ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy. With a MELD score of 36, he underwent successful OLT with the institution's immunosuppression protocol of basiliximab induction, steroid taper, mycophenolate modafinil and maintenance tacrolimus...Complications included cutaneous reaction to ampicillin requiring IV methylprednisolone and ruxolitinib due to initial concern for early GVHD which was later felt less likely based on timing and presentation characteristics. Sirolimus, used for immunosuppression/GVHD prophylaxis, was switched to tacrolimus due to possible cutaneous adverse reaction and was continued to prevent OLT rejection...Patients with SCD who have undergone liver transplantation can have significant risk of graft loss, with studies showing up to 22% requiring re-transplantation due to SCD complications. Our approach addresses both..."

Clinical • Bone Marrow Transplantation • CNS Disorders • Fibrosis • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Hepatic Encephalopathy • Hepatology • Immunology • Liver Cirrhosis • Sickle Cell Disease • Transplantation

Neural Correlates of Attentional Control: Localizing Locus Coeruleus Activity with fMRI and Pupillometry (Neuroscience 2025) - "To give specificity to our results, we utilized modafinil, an FDA-approved psychostimulant, to localize BOLD responses in the LC...These data were used to evaluate the hypothesis that LC activity is related to performance on sustained attention tasks. This work demonstrates the utility of direct measurement of a brain structure crucial in attentional control."

ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Mood Disorders • Psychiatry • Schizophrenia

Drug effects on sleep architecture and qEEG: a cross-species comparison in mice, rats and dogs. (Neuroscience 2025) - "Animals were dosed with modafinil (200 mg/kg p.o.) and recordings were made for 24 hours...These results indicate that, when attention is paid to the electrode type, the positioning on the skull, and the way in which the data is processed, highly comparable sleep and EEG responses to drugs can be detected across species. Sleep-EEG is, therefore, a powerful tool for confirming target engagement, pharmacodynamics and equivalent doses in both clinical and preclinical research."

Preclinical • CNS Disorders • Sleep Disorder

Phenotyping the DISC1 rat model of Schizophrenia using PPI, amphetamine-induced hyperlocomotion, sleep-EEG and 40Hz ASSR (Neuroscience 2025) - "In sleep-EEG the tgDISC1 rats had faster theta oscillations during wakefulness (F4.45,62.33=21.49 p<.001) which was fully reversed by modafinil (F2.63,21.06=16.97 p<.001). The tgDISC1 rat has a relatively mild phenotype on many of the measures used here, consistent with previously observations. However, while an absence of amphetamine sensitivity was unexpected, the reversal by risperidone of both impaired PPI and increased theta-frequency indicates the potential for the tgDISC1 rat in drug discovery for schizophrenia."

Preclinical • CNS Disorders • Psychiatry • Schizophrenia

Validation in Drosophila of the in silico predicted clomipramine as repurposable for SOD1-ALS. (PubMed, Neurotherapeutics) - "Current Food and Drug Administration-approved drugs -riluzole, edaravone, and tofersen - offer limited clinical benefit due to ALS multifactorial etiology and high heterogeneity...Leveraging the SAveRUNNER algorithm, we identified several potentially repurposable candidates, including clomipramine (Anafranil®), mianserin (Lantanon®/Tolvon®), and modafinil (Provigil®)...Our results demonstrate that clomipramine is the most promising candidate, ameliorating lifespan reduction, improving climbing abilities, and mitigating both genomic instability and inflammation, key pathological hallmarks of these SOD1-ALS models. Despite needing further validation in higher organisms, our Drosophila findings represent preliminary yet significant support for clomipramine's action as an add-on treatment for SOD1-ALS."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Respiratory Diseases

Repurposing immunomodulatory drugs targeting microglia for amyotrophic lateral sclerosis. (PubMed, Brain Res) - "Compounds such as ibudilast, fingolimod, and modafinil have shown encouraging initial clinical results, whereas others were well-tolerated but underpowered or failed to demonstrate efficacy. New candidates, such as azithromycin, naltrexone, montelukast, doxycycline, tofacitinib, quercetin, belinostat, and several kinase inhibitors, have demonstrated positive preclinical results, supporting their advancement toward clinical evaluation...To realize this potential, future studies must include larger cohorts, assess effects across disease stages and patient subgroups, and examine sex differences. This is essential to address patient heterogeneity and improve personalized treatment in ALS."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation

Prescription Stimulants Can Increase Risk of Arrhythmias: Systematic Review and Meta-Analysis (AHA 2025) - "These agents, including amphetamines, methylphenidate, modafinil, and lisdexamfetamine, elevate sympathetic tone and may precipitate cardiac arrhythmias, including atrial fibrillation (AF) and ventricular tachyarrhythmias. All major stimulant subclasses were significantly associated with increased arrhythmia risk, with the highest risk observed in amphetamines. These findings emphasize the potential cardiovascular consequences of stimulant therapy and reinforce the need for ongoing cardiac monitoring. Further research is warranted to delineate the safety profiles of individual stimulant medications."

Retrospective data • Review • ADHD (Impulsive Aggression) • Atrial Fibrillation • Attention Deficit Hyperactivity Disorder • Cardiovascular • CNS Disorders • Narcolepsy • Psychiatry • Sleep Disorder • Ventricular Tachycardia

Delayed Emergence From Anesthesia After EGD/Colonoscopy in a Patient With Undiagnosed Narcolepsy (ACG 2025) - "Prior cases suggest that preoperative modafinil or dextroamphetamine may facilitate faster emergence in those patients...This case underscores the critical need for detailed pre-procedural history-taking, including prior anesthesia responses and undiagnosed sleep disorders, to prevent unexpected post-sedation complications. Gastroenterologists and anesthesiologists should collaborate to optimize sedation strategies, particularly in patients with suspected or known narcolepsy."

Clinical • Anemia • Anesthesia • CNS Disorders • Endocrine Disorders • Gastrointestinal Disorder • Hematological Disorders • Narcolepsy • Polycystic Ovary Syndrome • Sleep Disorder

Pharmacological treatment options for cognitive dysfunction induced by multiple sclerosis: a network meta-analysis. (PubMed, Front Neurol) - "Compared to memantine, fampridine-SR, ginkgo biloba, and melatonin showed inferior effects. Atomoxetine may improve Symbol Digit Modalities Test (SDMT) scores, outperforming donepezil, ginkgo biloba, L-amphetamine, modafinil, and rivastigmine. Additionally, atomoxetine may improve California Verbal Learning Test (CVLT) performance, compared to ginkgo biloba, L-amphetamine, and memantine...However, rivastigmine was found to have a lower likelihood of causing dyspepsia among the treatments assessed. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024623642."

Journal • Retrospective data • Review • CNS Disorders • Cognitive Disorders • Dyspepsia • Multiple Sclerosis

Selenium Ameliorates Modafinil-Induced Male Reproductive Toxicity via Modulation of PI3K/Akt/NF-ҡB Pathway: Experimental Study and Molecular Docking Verification. (PubMed, J Biochem Mol Toxicol) - "The results demonstrated a significant improvement in the parameters when a Se dose of 0.2 mg/kg/day was co-administered. In conclusion, MOD interferes with male reproductive function in a dose-dependent manner, and Se may be a potentially helpful new approach for abating such toxicity."

Journal

Treatment of Orthostatic Intolerance (clinicaltrials.gov) - P1/2 | N=150 | Active, not recruiting | Sponsor: Satish R. Raj | Trial completion date: Dec 2027 ➔ Dec 2029 | Trial primary completion date: Dec 2027 ➔ Dec 2029

Trial completion date • Trial primary completion date • Cardiovascular

Maternal and offspring outcomes associated with prescribed ADHD medication in pregnancy: a systematic review. (PubMed, Arch Womens Ment Health) - "Women taking modafinil should consider stopping it prior to pregnancy. Clinicians should discuss the risks, benefits, and uncertainties of other ADHD medications with women who are pregnant, or considering pregnancy, keeping in mind that the benefits of continuing ADHD medications- where it is effective for an individual- are likely to outweigh the risks."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Gynecology • Psychiatry • Rare Diseases