The Effect of Adding Either Propofol or Ketamine to Magnesium and Lidocaine Infusions as An Opioid Free Anaesthesia on Surgical Field in Patients Undergoing Nasal Surgeries. A Randomized Controlled Trial

Nasal surgeries are common day case procedures. Although surgical complications are rare, bleeding decreases surgical field visibility and may cause vascular, orbital or intracranial complications in addition to failure of procedure. So, it is crucial to maintain hypotensive anaesthesia to optimize the surgical field.

Start Date15 Jun 2024

Sponsor / Collaborator

Ain Shams University

NCT06406647 / Not yet recruitingNot ApplicableIIT

Adding Ketamine as Adjuvant in Retroclavicular Block in Upper Limb Orthopedic Surgey

The ultrasound-guided retroclavicular approach to the infraclavicular region (RAPTIR) brachial plexus block has gained popularity as a relatively easy-to-perform nerve block that provides reliable and dense anesthesia to the upper extremity with a single injection. The block has been well described in the anesthesia community since it was first introduced by Hebbard and Royse in 2007 . In 2017, Luftig first described the block's use in the ED setting for a variety of indications . This nerve block has classically been described to provide extensive anesthesia for procedures distal to the shoulder, such as elbow dislocations, distal radius fractures, and surgical procedures.

Start Date01 Jun 2024

Sponsor / Collaborator-

NCT05803551 / Not yet recruitingPhase 2

A Phase II Randomized, Double Blind, Placebo-Controlled Study Evaluating the Effects of Ketamine Infusions in Clinically Depressed ICU Patients

The purpose of this research is to study the effects of intravenous ketamine infusions for the treatment of patients with depressive symptoms in intensive care unit (ICU).

Start Date01 Jun 2024

Sponsor / Collaborator

Mayo Clinic

100 Clinical Results associated with NRX-100

100 Translational Medicine associated with NRX-100

100 Patents (Medical) associated with NRX-100

18,102

Literatures (Medical) associated with NRX-100

05 Jul 2106·Oncotarget

The PI3K-AKT-mTOR pathway activates recovery from general anesthesia

Article

Author: Gao, Jin-Gui ; Song, Jian-Nan ; Cai, Jin-Song ; Zhang, Jin ; Zhang, Yun-Hui ; Zhou, Yang ; Xu, Xue

We investigated roles of PI3K-AKT-mTOR pathway in recovery from general anesthesia. Sprague-Dawley rats divided into five groups: saline+artificial cerebrospinal fluid (ACSF; Group A), ketamine+ACSF (Group B), ketamine+IGF-1 (Group C), ketamine+PI3K inhibitor (Group D), and PI3K/Akt agonists (Group E). Proportion of δ waves on ECoGs was recorded. Rats were tested for duration of loss of righting reflex (LORR), ataxic period and behavior in Morris water maze. mRNA and protein expression of members of PI3K-AKT-mTOR pathway were measured by RT-qPCR and Western blots. Histopathologic changes in hippocampal tissues observed by HE staining. We found that the proportion of δ waves decreased in Group C, while increased in Group D compared with Group B; the durations of LORR and ataxic period were shorter in Group C, but longer in Group D. In Morris water maze, escape latency (EL) and duration and frequency of staying on platform was shorter in Group C and longer in Group D than in Group B. Group A exhibited low expression of proteins in PI3K-AKT-mTOR pathway, while p-AKT, p-mTOR and p-P70S6K expression increased in cerebral cortex, brain stem, and thalamus in Group C. By contrast, expression of those proteins was lower in Group D than Group B. Those proteins expressions were higher in Group E than in Group A. HE staining showed that anesthesia may induce cell apoptosis in rat hippocampal CA1 areas, and PI3K/Akt agonists could inhibit apoptosis. Our results suggest that activation of PI3K-AKT-mTOR pathway may promote recovery from general anesthesia and enhance spatial learning and memory.

31 Dec 2024·European journal of psychotraumatology

So how special is special K? A systematic review and meta-analysis of ketamine for PTSD RCTs

Review

Author: Owen, Tyler ; Borgogna, Nicholas C ; Johnson, David A L ; Aita, Stephen L ; Vaughn, Jacob ; Hill, Benjamin D

Background: PTSD is a significant mental health problem worldwide. Current evidence-based interventions suffer various limitations. Ketamine is a novel agent that is hoped to be incrementally better than extant interventions.Objective: Several randomized control trials (RCTs) of ketamine interventions for PTSD have now been published. We sought to systematically review and meta-analyse results from these trials to evaluate preliminary evidence for ketamine's incremental benefit above-and-beyond control interventions in PTSD treatment.Results: Omnibus findings from 52 effect sizes extracted across six studies (n = 221) yielded a small advantage for ketamine over control conditions at reducing PTSD symptoms (g = 0.27, 95% CI = 0.03, 0.51). However, bias-correction estimates attenuated this effect (adjusted g = 0.20, 95%, CI = -0.08, 0.48). Bias estimates indicated smaller studies reported larger effect sizes favouring ketamine. The only consistent timepoint assessed across RCTs was 24-hours post-initial infusion. Effects at 24-hours post-initial infusion suggest ketamine has a small relative advantage over controls (g = 0.35, 95% CI = 0.06, 0.64). Post-hoc analyses at 24-hours post-initial infusion indicated that ketamine was significantly better than passive controls (g = 0.44, 95% CI = 0.03, 0.85), but not active controls (g = 0.24, 95% CI = -0.30, 0.78). Comparisons one-week into intervention suggested no meaningful group differences (g = 0.24, 95% CI = 0.00, 0.48). No significant differences were evident for RCTs that examined effects two-weeks post initial infusion (g = 0.17, 95% CI = -0.10, 0.44).Conclusions: Altogether, ketamine-for-PTSD RCTs reveal a nominal initial therapeutic advantage relative to controls. However, bias and heterogeneity appear problematic. While rapid acting effects were observed, all control agents (including saline) also evidenced rapid acting effects. We argue blind penetration to be a serious concern, and that placebo is the likely mechanism behind reported therapeutic effects.

01 Jun 2024·IBRO neuroscience reports

Antipsychotic effect of diosgenin in ketamine-induced murine model of schizophrenia: Involvement of oxidative stress and cholinergic transmission

Article

Author: Emuakpeje, Micheal T ; Fokoua, Aliance Romain ; Oritsemuelebi, Benjamin ; Uyere, God'swill E ; Kumanwee, Lenatababari ; Ben-Azu, Benneth ; Adebayo, Olusegun G ; Chidebe, Emmanuel O ; Nwogueze, Chukwuebuka B

A decrease in the levels of antioxidant arsenals exacerbate generation of reactive oxygen/nitrogen species, leading to neurochemical dysfunction, with significant impact on the pathogenesis of psychotic disorders such as schizophrenia. This study examined the preventive and reversal effects of diosgenin, a phyto-steroidal saponin with antioxidant functions in mice treated with ketamine which closely replicates schizophrenia-like symptoms in human and laboratory animals. In the preventive phase, adult mice cohorts were clustered into 5 groups (n = 9). Groups 1 and 2 received saline (10 mL/kg, i.p.), groups 3 and 4 were pretreated with diosgenin (25 and 50 mg/kg), and group 5 received risperidone (0.5 mg/kg) orally for 14 days. Mice in groups 2-5 additionally received a daily dose of ketamine (20 mg/kg, i.p.) or saline (10 mL/kg/day, i.p.). In the reversal phase, mice received intraperitoneal injection of ketamine or saline for 14 consecutive days prior to diosgenin (25 and 50 mg/kg/p.o./day) and risperidone (0.5 mg/kg/p.o./day) treatment from days 8-14. Mice were assessed for behavioral changes. Oxidative, nitrergic markers, and cholinergic (acetylcholinesterase activity) transmission were examined in the striatum, prefrontal-cortex and hippocampus. Diosgenin prevented and reversed hyperlocomotion, cognitive and social deficits in mice treated with ketamine relative to ketamine groups. The increased acetylcholinesterase, malondialdehyde and nitrite levels produced by ketamine were reduced by diosgenin in the striatum, prefrontal-cortex and hippocampus, but did not reverse striatal nitrite level. Diosgenin increased glutathione, and catalase levels, except for hippocampal catalase activity when compared with ketamine controls. Conclusively, these biochemical changes might be related to the behavioral deficits in ketamine-treated mice, which were prevented and reversed by diosgenin.

137

News (Medical) associated with NRX-100

29 May 2024

·www.prnewswire.com

Johnson & Johnson pivotal study of seltorexant shows statistically significant and clinically meaningful improvement in depressive symptoms and sleep disturbance outcomes

Seltorexant, an investigational first-in-class therapy, met all primary and secondary endpoints in pivotal Phase 3 study in patients with major depressive disorder (MDD) with insomnia symptoms, as presented at ASCP 2024 Approximately 60 percent of MDD patients on standard-of-care oral antidepressants experience residual insomnia symptoms1, underscoring the high level of unmet need Positive topline results for SPRAVATO® (esketamine) CIII nasal spray as a monotherapy were also presented, demonstrating rapid and sustained efficacy in treatment-resistant depression (TRD) TITUSVILLE, N.J., May 29, 2024 /PRNewswire/ -- Johnson & Johnson announced today positive topline results from the pivotal Phase 3 MDD3001 clinical trial evaluating the efficacy and safety of seltorexant as an adjunctive treatment to baseline antidepressants in adult and elderly patients with major depressive disorder (MDD) with insomnia symptoms. Seltorexant is an investigational first-in-class selective antagonist of the human orexin-2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. The findings will be presented at this year's American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, which is being held from May 28-31 in Miami, Florida. The Phase 3 randomized, double-blind, multicenter, placebo-controlled study achieved all primary and secondary endpoints, with seltorexant demonstrating both a statistically significant and clinically meaningful improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at day 43, and improved sleep disturbance outcomes, in patients who had a prior inadequate response to SSRI/SNRI antidepressants alone. These results were observed in a patient population that was assessed to be moderately-to-severely depressed despite ongoing treatment with SSRI/SNRIs and suffered from significant sleep disturbance. Seltorexant was also safe and well-tolerated in the study, with similar rates of common adverse events seen in both trial arms, consistent with previous seltorexant clinical trials. "Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs and impact quality of life, and it often goes under treated despite being one of the most common residual symptoms2,3,4," said Andrew Krystal, MD, Professor, Psychiatry, University of California, San Francisco Weill Institute for Neurosciences. "Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia, and most importantly, to improve outcomes and quality of life for these patients." MDD is often accompanied by sleep disturbances such as insomnia or hypersomnia. With insomnia, patients may have trouble falling asleep, staying asleep, or getting good quality sleep. Approximately 60 percent of MDD patients on standard-of-care oral antidepressants experience residual insomnia symptoms.1 Currently, no therapies are approved to treat MDD with insomnia symptoms. "For nearly seven decades, Johnson & Johnson has delivered transformational treatments and solutions for people living with serious mental illness, and we are proud to present these data from our marketed and late-stage neuropsychiatry portfolios at ASCP," said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience. "As global leaders, we must continue to drive innovation in the treatment of depression, bringing new mechanisms of action and potentially first-in-class therapies to the millions of people living with mental health disorders." DELIVERING RAPID AND SUSTAINED EFFICACY FOR TREATMENT-RESISTANT DEPRESSION (TRD) Additional data presented at ASCP includes positive topline results from the placebo-controlled Phase 4 TRD4005 study of SPRAVATO® (esketamine) CIII nasal spray as a monotherapy in patients with TRD, which met both its primary and secondary endpoints. The randomized, double-blind, multicenter study showed SPRAVATO® provided rapid, statistically significant, and clinically meaningful improvement in depressive symptoms ~24 hours after the first dose and sustained through 4 weeks of treatment, as assessed by changes in MADRS total score. The safety profile of SPRAVATO® monotherapy was consistent with the registration Phase 3 studies of TRD in combination with an oral antidepressant, and no new safety concerns were identified. SPRAVATO® is approved by the U.S. Food and Drug Administration (FDA), in combination with an oral antidepressant, for adults with TRD and depressive symptoms in adults with MDD with suicidal thoughts or behaviors. With its approval in 2019, SPRAVATO® offered the first novel mechanism of action in decades for the treatment of MDD. To date, SPRAVATO® has been administered to more than 100,000 people living with challenging-to-treat forms of depression around the world. Other accepted data at ASCP showcase our innovative data science usage in MDD research, including leveraging machine learning and similar measures that support our precision approach to neuropsychiatry. A complete listing of Company-sponsored abstracts can be viewed here. ABOUT SELTOREXANT Seltorexant, an investigational first-in-class therapy, is a selective antagonist of the human orexin-2 receptor currently being developed as an adjunctive treatment for adults with MDD with insomnia symptoms. Seltorexant selectively antagonizes the orexin-2 receptors, potentially improving mood and sleep symptoms associated with depression. When orexin-2 receptors are stimulated for too long or at inappropriate times, their activation can cause hyperarousal manifestations, including insomnia and excessive cortisol release, which may contribute to depression and insomnia. ABOUT MDD3001 The Phase 3 MDD3001 study was a randomized, double-blind, multicenter, placebo-controlled study designed to compare the efficacy and safety of oral, once daily seltorexant 20 milligrams to that of placebo, adjunctive to background SSRI/SNRI, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms. ABOUT MAJOR DEPRESSIVE DISORDER WITH INSOMNIA SYMPTOMS MDD is one of the most common psychiatric disorders and leading causes of disability worldwide,5 with an estimated 280 million people living with the disorder around the world.6 MDD is often accompanied by sleep disturbances such as insomnia or hypersomnia, with approximately 60 percent of MDD patients experiencing insomnia symptoms despite being on an SSRI/SNRI.1 Disturbed sleep and insomnia symptoms have a significant impact on a patient's quality of life and exacerbate the risk of depressive relapse and suicide.2,4 ABOUT SPRAVATO® SPRAVATO® (esketamine) CIII nasal spray is approved by the U.S. Food and Drug Administration in combination with an oral antidepressant for adults with TRD and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. It is the first novel mechanism of action in decades for the treatment of MDD. SPRAVATO® is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor and is believed to work differently by acting on a pathway in the brain that affects glutamate. To date, SPRAVATO® has been approved in 77 countries and administered to more than 100,000 patients worldwide. ABOUT TRD4005 The Phase 4 TRD4005 clinical trial was a randomized, double-blind, multicenter, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of esketamine monotherapy at either 56 milligrams or 84 milligrams, administered bi-weekly, compared with placebo nasal spray in improving depressive symptoms in adult patients with TRD. ABOUT TREATMENT-RESISTANT DEPRESSION It is estimated that at least 30 percent of people living with MDD have treatment-resistant depression, which is defined as not responding to at least two or more different antidepressants of adequate dose and duration.7 TRD has a significant negative impact, emotionally and functionally, on the individual and their loved ones, and has one of the highest economic burdens of all psychiatric disorders.7 IMPORTANT SAFETY INFORMATION What is SPRAVATO® (esketamine) CIII nasal spray? SPRAVATO® is a prescription medicine, used along with an antidepressant taken by mouth to treat: Adults with treatment-resistant depression (TRD) Depressive symptoms in adults with major depressive disorder (MDD) with suicidal thoughts or actions SPRAVATO® is not for use as a medicine to prevent or relieve pain (anesthetic). It is not known if SPRAVATO® is safe or effective as an anesthetic medicine. It is not known if SPRAVATO® is safe and effective for use in preventing suicide or in reducing suicidal thoughts or actions. SPRAVATO® is not for use in place of hospitalization if your healthcare provider determines that hospitalization is needed, even if improvement is experienced after the first dose of SPRAVATO®. It is not known if SPRAVATO® is safe and effective in children. IMPORTANT SAFETY INFORMATION Do not take SPRAVATO® if you: have blood vessel (aneurysmal vascular) disease (including in the brain, chest, abdominal aorta, arms and legs) have an abnormal connection between your veins and arteries (arteriovenous malformation) have a history of bleeding in the brain are allergic to esketamine, ketamine, or any of the other ingredients in SPRAVATO®. If you are not sure if you have any of the above conditions, talk to your healthcare provider before taking SPRAVATO®. Before you take SPRAVATO®, tell your healthcare provider about all of your medical conditions, including if you: have heart or brain problems, including: high blood pressure (hypertension) slow or fast heartbeats that cause shortness of breath, chest pain, lightheadedness, or fainting history of heart attack history of stroke heart valve disease or heart failure history of brain injury or any condition where there is increased pressure in the brain have liver problems have ever had a condition called "psychosis" (see, feel, or hear things that are not there, or believe in things that are not true). are pregnant or plan to become pregnant. SPRAVATO® may harm your baby. You should not take SPRAVATO® if you are pregnant. Tell your healthcare provider right away if you become pregnant during treatment with SPRAVATO®. If you are able to become pregnant, talk to your healthcare provider about methods to prevent pregnancy during treatment with SPRAVATO®. There is a pregnancy registry for women who are exposed to SPRAVATO® during pregnancy. The purpose of the registry is to collect information about the health of women exposed to SPRAVATO® and their baby. If you become pregnant during treatment with SPRAVATO®, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or online at programs/pregnancyregistry/antidepressants/. are breastfeeding or plan to breastfeed. You should not breastfeed during treatment with SPRAVATO®. Tell your healthcare provider about all the medicines that you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Taking SPRAVATO® with certain medicine may cause side effects. Especially tell your healthcare provider if you take central nervous system (CNS) depressants, psychostimulants, or monoamine oxidase inhibitors (MAOIs) medicines. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. How will I take SPRAVATO®? You will take SPRAVATO® nasal spray yourself, under the supervision of a healthcare provider in a healthcare setting. Your healthcare provider will show you how to use the SPRAVATO® nasal spray device. Your healthcare provider will tell you how much SPRAVATO® you will take and when you will take it. Follow your SPRAVATO® treatment schedule exactly as your healthcare provider tells you to. During and after each use of the SPRAVATO® nasal spray device, you will be checked by a healthcare provider who will decide when you are ready to leave the healthcare setting. You will need to plan for a caregiver or family member to drive you home after taking SPRAVATO®. If you miss a SPRAVATO® treatment, your healthcare provider may change your dose and treatment schedule. Some people taking SPRAVATO® get nausea and vomiting. You should not eat for at least 2 hours before taking SPRAVATO® and not drink liquids at least 30 minutes before taking SPRAVATO®. If you take a nasal corticosteroid or nasal decongestant medicine take these medicines at least 1 hour before taking SPRAVATO®. What should I avoid while taking SPRAVATO®? Do not drive, operate machinery, or do anything where you need to be completely alert after taking SPRAVATO®. Do not take part in these activities until the next day following a restful sleep. See "What is the most important information I should know about SPRAVATO®?" What are the possible side effects of SPRAVATO®? SPRAVATO® may cause serious side effects including: See "What is the most important information I should know about SPRAVATO®?" Increased blood pressure. SPRAVATO® can cause a temporary increase in your blood pressure that may last for about 4 hours after taking a dose. Your healthcare provider will check your blood pressure before taking SPRAVATO® and for at least 2 hours after you take SPRAVATO®. Tell your healthcare provider right away if you get chest pain, shortness of breath, sudden severe headache, change in vision, or seizures after taking SPRAVATO®. Problems with thinking clearly. Tell your healthcare provider if you have problems thinking or remembering. Bladder problems. Tell your healthcare provider if you develop trouble urinating, such as a frequent or urgent need to urinate, pain when urinating, or urinating frequently at night. The most common side effects of SPRAVATO® when used along with an antidepressant taken by mouth include: If these common side effects occur, they usually happen right after taking SPRAVATO® and go away the same day. These are not all the possible side effects of SPRAVATO®. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please see full Prescribing Information , including Boxed WARNINGS, and Medication Guide for SPRAVATO® and discuss any questions you may have with your healthcare provider. cp-170363v3 ABOUT JOHNSON & JOHNSON At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and where solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies. CAUTIONS CONCERNING FORWARD-LOOKING STATEMENTS This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of seltorexant and SPRAVATO®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products, and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of healthcare products and services; changes to applicable laws and regulations, including global healthcare reforms; and trends toward healthcare cost containment. A further list and descriptions of these risks, uncertainties, and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the U.S. Securities and Exchange Commission. Copies of these filings are available online at , , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. © Johnson & Johnson 2024. All rights reserved. SOURCE Johnson & Johnson

Clinical ResultPhase 3Drug Approval

28 May 2024

·www.prnewswire.com

AANA Issues Updated Practice Considerations for Ketamine Therapy for Psychiatric Disorders and Chronic Pain Management

ROSEMONT, Ill., May 28, 2024 /PRNewswire/ -- The American Association of Nurse Anesthesiology (AANA) recently updated its practice considerations addressing ketamine therapy to cite the most current studies, as AANA continues to support a patient-centered, interdisciplinary approach to providing care and treatment to persons with psychiatric disorders or chronic pain. Included in these revised considerations is the use of esketamine nasal spray, an FDA-approved treatment for treatment-resistant depression (TRD) in adults and depressive symptoms in patients with major depressive disorder (MDD). Ketamine therapy has been shown to have antidepressive properties and is increasingly being used to treat psychiatric disorders, including major depressive disorder, bipolar disorder, treatment-resistant depression, and post-traumatic stress disorder. Certified Registered Nurse Anesthetists (CRNAs), also known as nurse anesthesiologists or nurse anesthetists, have extensive training in the delivery of pain management medications such as ketamine and management of associated side effects or complications. The updated practice considerations feature a greatly expanded pharmacologic review section. "CRNAs are highly trained in delivering professional, compassionate anesthesia and related care and have the expertise to safely administer all forms of ketamine, making their involvement a valuable solution. Their ability to provide anesthesia services autonomously in various healthcare settings can increase the availability of this therapy, especially in remote or underserved areas," said Tracy Young, MSNA, MBA, CRNA, and member of AANA's Board of Directors. "These updated ketamine practice considerations are based on the most current literature identified through AANA's evidence-based process and give CRNAs a comprehensive analysis of this unique area of practice." When administering ketamine for treatment of psychiatric disorders, CRNAs collaborate with psychiatric-mental health professionals whose practice includes diagnosing psychiatric disorders within their professional and state scope of practice. The practice considerations advise the importance of continued screening, monitoring, and follow-up of patients with psychiatric disorders or chronic pain throughout treatment and management. With ketamine infusion clinics becoming more available, CRNAs or other qualified anesthesia providers should participate in the creation, review and periodic updating of evidence-based policies and procedures at the clinics and evaluation of the availability of necessary routine and emergency monitors, supplies, and equipment. "CRNAs' education in pharmacology and holistic approach to patient care, including their strong focus on patient education and emotional support, can help reduce the stigma surrounding ketamine therapy and mental health treatments and improve patients' acceptance," Young said. The CRNA's role in ketamine infusion therapy may include, but is not limited to, reviewing healthcare records; obtaining a health history; conducting a pre-infusion assessment and evaluation; ordering and evaluating diagnostic tests; ordering or prescribing medications; initiating, maintaining, titrating, and discontinuing the infusion; monitoring the patient; and conducting post-infusion assessment and evaluation. SOURCE American Association of Nurse Anesthesiology

28 May 2024

·www.biospace.com

NRx Pharmaceuticals (Nasdaq:NRXP) Presents Landmark Trial of NRX-101 in Suicidal Bipolar Depression At the ASCP Annual Meeting: NRX-101 is the First Oral Antidepressant Demonstrated to Reduce Suicidality in Bipolar

Poster presentation of "A Randomized, Double-Blind Controlled Comparison of NRX-101 (D-cycloserine/lurasidone) to Lurasidone for Adults with Bipolar Depression and Subacute Suicidal Ideation or Behavior" NRX-101 demonstrated a similar antidepressant effect (MADRS reduction ~50%) compared to lurasidone, the Standard of Care drug NRX-101 demonstrated a 58% relative reduction in time to sustained remission from suicidality (P=.05) compared to lurasidone NRX-101 demonstrated a 76% reduction in symptoms of akathisia (p=0.03), a side effect linked to suicide, compared to lurasidone This represents the second trial of NRX-101 demonstrating reduction in suicidality and akathisia associated with NRX-101 compared to lurasidone RADNOR, Pa., May 28, 2024 /PRNewswire/ -- NRx Pharmaceuticals, Inc. (Nasdaq: NRXP) ("NRx Pharmaceuticals", "NRx", the "Company"), a clinical stage pharmaceutical company, today announced presentation of its Phase 2b/3 trial of NRX-101, entitled "A Randomized, Double-Blind Controlled Comparison of NRX-101 (D-cycloserine/lurasidone) to Lurasidone for Adults with Bipolar Depression and Subacute Suicidal Ideation or Behavior" at the American Society of Clinical Psychopharmacology (ASCP) in Miami Beach, FL. The lead author is Prof. Andrew Nierenberg, Director, Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital and Professor of Psychiatry, Harvard Medical School. "Presentation of these data at this highly respected conference is another important step toward bringing a life-saving product to patients in tremendous need," said Dr. Jonathan Javitt, Chairman and Chief Scientist of NRx. "We believe that NRX-101 may offer a paradigm changing approach to treatment of Bipolar Depression, with a product highly effective in both treating depression and reducing suicidality and associated side effects. We will continue working to bring hope to life with life-saving medications." The presentation will be held at 11:15 AM, Wednesday May 29, 2024. W89 A Randomized, Double-Blind Controlled Comparison of NRX-101 (D-cycloserine/lurasidone) to Lurasidone for Adults with Bipolar Depression and Subacute Suicidal Ideation or Behavior CONCLUSIONS of the Poster are: NRX-101 and lurasidone both demonstrated > 50% response for treating bipolar depression with no difference seen on primary efficacy endpoint (MADRS) A clinically meaningful difference was observed on both primary and secondary safety endpoints favoring NRX-101 NRX-101 was associated with 58% relative reduction in time to sustained remission from suicidality as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) when stratified by sex, mood stabilizer use, antipsychotic use, lifetime suicide event (P=0.05). NRX-101 was associated with a relative 76% reduction in symptoms of akathisia compared to lurasidone that was sustained over 42 days (Effect Size 0.37; P=0.03) on the Barnes Akathisia Rating Scale Akathisia was seen in 2% of participants treated with NRX-101 vs. 11% treated with lurasidone. NRX-101 showed superiority to lurasidone in akathisia starting at day 7 and continuing through day 42/ET. No treatment-related serious adverse event was observed in either group. No safety issues were detected except for MedDRA General disorders: NRX-101 - 18.2% vs lurasidone - 0% (p=0.002). Based on these findings, together with the earlier STABIL-B trial, the Company believes that NRX-101 has potential to become a standard of care drug for treating bipolar depression, an addressable population of 7 million patients in the US and many times that around the world. This study represents the second trial conducted under FDA Good Clinical Practices guidelines to demonstrate large and meaningful advantages of NRX-101 vs lurasidone on akathisia and suicidality and clears the path for a registration trial of NRX-101 vs. placebo to treat bipolar depression together with earlier accelerated approval for those with akathisia. An additional academic trial conducted by Chen and co-workers similarly demonstrated a statistically-significant reduction in suicidality associated with D-cycloserine, the active ingredient in NRX-101, compared to various standard of care antidepressants. To the Company's knowledge, this trial and its prior STABIL-B study represent the only clinical trials in which an oral antidepressant has been demonstrated to cause meaningful reductions in suicidality and akathisia. All currently approved antidepressant drugs carry FDA-mandated "black box" warnings on their labels indicating that they may increase the risk of suicide. Similarly, akathisia – a side effect in which patients are agitated and frequently experience involuntary movement – is a side effect that occurs in 10-15% of patients who take the lurasidone class of drugs and is closely linked to suicide. As shown in the clinical trial, those randomized to lurasidone experienced a substantial increase in akathisia from baseline, whereas those randomized to NRX-101 demonstrated a statistically-significant reduction in akathisia (see Figure). About NRx Pharmaceuticals NRx Pharmaceuticals is a clinical-stage biopharmaceutical company developing therapeutics based on its NMDA platform for the treatment of central nervous system disorders, specifically suicidal bipolar depression, chronic pain and PTSD. The Company is developing NRX-101, an FDA-designated investigational Breakthrough Therapy for suicidal treatment-resistant bipolar depression and chronic pain. NRx has partnered with Alvogen and Lotus around the development and marketing of NRX-101 for the treatment of suicidal bipolar depression. NRX-101 additionally has potential to act as a non-opioid treatment for chronic pain, as well as a treatment for complicated UTI. NRx has recently announced plans to submit a New Drug Application for HTX-100 (IV ketamine), through Hope Therapeutics, in the treatment of suicidal depression, based on results of well-controlled clinical trials conducted under the auspices of the US National Institutes of Health and newly obtained data from French health authorities, licensed under a data sharing agreement. NRx was awarded Fast Track Designation for development of ketamine (NRX-100) by the US FDA as part of a protocol to treat patients with acute suicidality. Notice Regarding Forward-Looking Statements The information contained herein includes forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended. These statements include, among others, statements regarding the proposed public offering and the timing and the use of the proceeds from the offering. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "expect," "plan," "believe," "intend," "look forward," and other similar expressions among others. These statements relate to future events or to the Company's future financial performance, and involve known and unknown risks, uncertainties and other factors that may cause the Company's actual results to be materially different from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. You should not place undue reliance on forward-looking statements since they involve known and unknown risks, uncertainties and other factors which are, in some cases, beyond the Company's control and which could, and likely will, materially affect actual results, levels of activity, performance or achievements. Any forward-looking statement reflects the Company's current views with respect to future events and is subject to these and other risks, uncertainties and assumptions relating to the Company's operations, results of operations, growth strategy and liquidity. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's most recent Annual Report on Form 10-K and other filings with the Securities and Exchange Commission. Investors and security holders are urged to read these documents free of charge on the SEC's website at . Except as may be required by applicable law, The Company assumes no obligation to publicly update or revise these forward-looking statements for any reason, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, whether as a result of new information, future events or otherwise. View original content to download multimedia: SOURCE NRx Pharmaceuticals, Inc. Company Codes: NASDAQ-NMS:NRXP

Clinical ResultFast TrackBreakthrough TherapyASCO

100 Deals associated with NRX-100

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bipolar and Related Disorders	Phase 3	US	NeuroRx, Inc.	30 Jan 2022
Bipolar Disorder	Phase 3	US	NRX Pharmaceuticals, Inc.	21 Dec 2021

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05193318 (CTgov)	Phase 2	Depression \| Depressive Disorder, Major \| Opium Dependence	5	Ketamine-assisted psychotherapy	pqbvsqbcqh(hofiiypqqc) = avnbuekhst brvmcuqddo (ppnqvhzlzs, gemndyyvam - uldxywwryq) View more	-	06 May 2024
AAN2023	Not Applicable	Headache	4	Continuous Ketamine Infusion	bjyjxalglh(laxpuyovrp) = Few transient adverse events were reported, including dysarthria and somnolence, which resolved spontaneously nlqutraqej (kxapyamtav ) View more	Positive	25 Apr 2023
GlobeNewswire Manual	Phase 1/2	Dyskinesias \| Parkinson Disease	10	ketamine	kahmnwhxod(xhdcmcukyq) = acgrjaukpo ayzxdegatd (bsiwusngxn ) View more	Positive	14 Nov 2022
GlobeNewswire Manual	Phase 1/2	Parkinson Disease	10	Ketamine	dxwbwosohm(brrrkdjaxx) = yvsrvzqhsi ypsgwrmdik (iumlslyeth ) View more	Positive	16 Sep 2022
NCT03909607 (CTgov)	Phase 4	Pain	120	Ketamine 0.75 mg/kg (SDK 0.75 mg/kg)	dfodjhirli(fpyanjppnk) = fexkbyaizq nldemrnyoe (edzjnchcuk, xtsssqemat - cqmnfcqlov) View more	-	03 May 2022
				Ketamine 1.0 mg/kg (SDK 1.0 mg/kg)	dfodjhirli(fpyanjppnk) = tolctismiz nldemrnyoe (edzjnchcuk, caeluraitp - ujxejyljxw) View more
ASN2021	Not Applicable	Diabetes Insipidus	-	Ketamine infusion	bnqelgmbxl(nxzhzslerb) = 5 indicating a probable ADR imsdozisgb (hvlhwzjnjc ) View more	Positive	27 Oct 2021
				Desmopressin
Pubmed	Not Applicable	Adjuvant	750	Intrathecal Bupivacaine + Ketamine	oriaoolcaa(iicobrujox) = bubrrworfb ntmvtqdefh (acnvksibcx, 3.27 - 4.78) View more	Positive	01 Oct 2021
Pubmed \| Mult Scler	Not Applicable	Fatigue	18	Ketamine (0.5 mg/kg)	pxxndbbgra(nbbznxxsgp): P-Value = 0.04	-	01 May 2021
				Midazolam (0.05 mg/kg)
1642 (AAN2020)	Not Applicable	Fatigue	18	Ketamine	vkyujyqgeo(ffqktmlmpb): P-Value = 1-week View more	-	14 Apr 2020
				Midazolam
PO001 (AAO2018)	Not Applicable	Sedation	610	Diazepam (Valium)	onnqankrwr(ckydlohvph) = lhwconshhv epcukiiqkv (glbbohhaxt ) View more	Positive	28 Oct 2018
				Diazepam/Tramadol/Ondansetron	onnqankrwr(ckydlohvph) = alkbpyysze epcukiiqkv (glbbohhaxt ) View more

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