A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin re-uptake inhibitors and lofepramine

开始日期1999-02-01

申办/合作机构-

100 项与 AF-4025 相关的临床结果

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100 项与 AF-4025 相关的专利（医药）

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657

项与 AF-4025 相关的文献（医药）

2025-12-01·JOURNAL OF AFFECTIVE DISORDERS

Prebiotics chronotherapy alleviates depression-like behaviors in FMT mice through enhancing short-chain fatty acids receptors and intestinal barrier

Article

作者: Ma, Xiuyun ; Zhang, Shuo ; Shen, Jinlin ; An, Bei ; Li, Yuhao ; Li, Chuying ; Cao, Pengpeng ; Sun, Yanzhuang

BACKGROUND:

Prebiotics interventions to restore microbiome homeostasis may have long-lasting benefits for mental health especially in adolescence. However, the anti-depressants of prebiotics, particularly in prebiotics chronotherapy, orchestrated remain unknown. We aimed to elucidate the underlying mechanisms of prebiotics in light of maximum antidepressant effects by appropriate dosing timing.

METHODS:

Adolescent depression mouse model was made by fecal microbiota transplantation (FMT) from major depressive disorder (MDD) adolescent patients. Sodium Butyrate (SB), one of SCFAs, was intragastrically administrated to mice at Zeitgeber time 4 (ZT4: the highest short-chain fatty acids (SCFAs) receptor-activated timing) or ZT16 (the lowest SCFA receptor-activated timing) for the last 2 weeks within 4-week-FMT exposure. The success of modeling and antidepressant effects of SB chronotherapy were determined by changes in depression-like behaviors, inflammation, neurotrophy, neuron functions, circadian rhythm, and barrier systems.

RESULTS:

SB alleviated depressive symptoms at ZT4 with better efficacy over ZT16. SB decreased inflammation, upregulated neurotrophy, restored functions, and re-established circadian rhythm. Notably, SB increased the expressions of SCFAs receptors to repair the intestinal barrier and blood-brain barrier, thereby alleviating depressive symptoms.

LIMITATION:

Only one prebiotic with one disease was involved.

CONCLUSION:

SB supplementation could be a promising therapeutic tactic for restoring the integrity of barrier systems by enhancing the intestinal SCFAs receptors. Alignment SB supplementation with circadian clocks might help to obtain better antidepressant efficacy, which may generate novel insights into diseases related to diseases with barrier system impairment and optimize interventions to improve health and human well-being.

2025-12-01·PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY

Involvement of dimethylarginine dimethylaminohydrolase type 1 (DDAH1) in addiction and social stress phenotypes: Insights from proteomic, metabolomic and functional studies

Review

作者: Briand, Lisa A ; Nenov, Miroslav N

Nitric oxide synthase (NOS) plays a role in substance use related neurotoxicity and addictive phenotypes. Inhibition of nitric oxide (NO) production can prevent negative phenotypes associated with drugs intake. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. ADMA levels are regulated by dimethylarginine dimethylaminohydrolase type 1 (DDAH1). Numerous evidence suggests that drugs of abuse can increase DDAH1 levels, leading to reduction of ADMA levels, and in turn, causing neurotoxicity associated with NO overproduction. Yet, this data is sparse, and very little mechanistic evidence exists. Here, we review the literature on the impact of substances of abuse and social stress, as a condition implicated in addictive phenotypes, on DDAH1 levels in the brain. This review highlights five things: first, psychostimulants can increase brain DDAH1 levels and DDAH1-ADMA-NOS signaling axis could underlay neurotoxicity and addictive behaviors driven by psychostimulants. Second, opioids can also significantly increase brain DDAH1 levels, yet currently no mechanistic studies exist to determine the consequences of that increase. Three, the nicotine and alcohol studies are inconclusive as results are often complicated with comorbidities associated with cardiovascular impairments, liver toxicity and aging. Four, studies on cannabinoids are insufficient, more data is needed. Finally, social stress affects DDAH1 levels and anti-depressants can reverse this effect, but mechanistic data is lacking. In conclusion, proteomic, metabolomic and functional studies suggest that DDAH1 may play a role in addiction and conditions related to social stress. Further investigation is necessary to elucidate the specific function of DDAH1 in addiction and social stress phenotypes.

2025-11-01·JOURNAL OF NEUROIMMUNOLOGY

Immunostimulatory and immunomodulatory effects of duloxetine and venlafaxine on p38 MAPK and PI3K pathways

Article

作者: Ayaz, Furkan ; Yetkin, Derya ; Aydemir, Esra

Anti-depressants have been used more widely throughout the world. Their mood altering activities are appreciated but determining their side effects or possible effects on the immune system is crucial. In our study, we focused on two prominent drugs that have been used against anxiety and depression. Serotonin and norepinephrine reuptake inhibitor (SNRI) anti-depressants Duloxetine and Venlafaxine were tested in vitro on the mammalian macrophages. Their immunostimulatory (inflammatory potential) activities were tested on inactivated macrophages whereas their immunomodulatory, possible anti-inflammatory activities were tested on the LPS activated macrophages. The production levels of pro-inflammatory cytokines were measured by ELISA. The levels of phosphorylated (active) p38 MAPK and PI3K proteins were determined by flow cytometry analysis and their possible intracellular mechanisms of action were demonstrated. According to our results, these drugs had differential effects on the macrophages. Duloxetine triggered a mild inflammatory response in the unactivated macrophages whereas; it had anti-inflammatory effects on already activated macrophages. Venlafaxine lacked this immunostimulatory activity on unactivated macrophages and had mild anti-inflammatory activities on the activated macrophages. These results suggest that these drugs can be differentially utilized against patients with inflammatory problems (Duloxetine) and patients without inflammatory problems (Venlafaxine).

项与 AF-4025 相关的新闻（医药）

2025-10-29

·EINPresswire

Free ‘morning after pill’ for women at high street pharmacies thanks to NHS expansion

Women will be able to access the morning-after pill free of charge on the NHS in high-street pharmacies across England from today. In the “biggest change to sexual health services since the 1960s”, the oral emergency contraception pill will be available for free to women from almost 10,000 pharmacies across the country without needing to see their GP or get an appointment at a sexual health clinic. As part of a major expansion of pharmacy services announced by NHS England, people starting treatment with anti-depressants will also be able to seek additional advice and support about their medication and healthy lifestyle changes from their local pharmacist. Earlier this year, pharmacies also began offering oral contraceptive pill consultations and repeat supplies, allowing women to start or continue the supply of their regular contraception from their local pharmacy. The initiative is part of a wider package of support for community pharmacies and expanding access to NHS services, helping people to get the care they need in convenient, familiar settings. From today, people who have been newly prescribed antidepressants will also be able to seek additional advice and support about their medication and healthy lifestyle changes from their local pharmacist. Anyone aged 18 collecting their new prescription for anti-depressants will be able to get more information from their local pharmacist about how the medication is working and address any concerns they may have, they can also arrange a follow up telephone chat if they prefer. Dr Sue Mann, NHS National Clinical Director in Women’s Health , said: “This is one of the biggest changes to sexual health services since the 1960s and a game-changer in making reproductive healthcare more easily accessible for women. “Instead of trying to search for women’s services or explain their needs, from today women can just pop into their local pharmacy and get the oral emergency contraceptive pill free of charge without needing to make an appointment. “Community pharmacists and their teams are trusted professionals who women will be able to speak to confidentially and address any concerns they may have. “With 4 in 5 people living within a 20-minute walk from a pharmacy this service is another example of how the NHS is already delivering on our 10 Year Health Plan commitment to shift care into the heart of communities.” Community pharmacies are staffed by pharmacists who are skilled and qualified health professionals who are ready to provide advice and support, helping patients access emergency contraception or extra guidance on their anti-depressant medication as part of routine community healthcare services. They are at the heart of local healthcare and are playing a bigger role as the NHS shifts care into the community. As well as over-the-counter support and treatment for minor health concerns, community pharmacy services can also supply prescription-only medicines, such as antibiotics and antivirals where clinically appropriate, to treat common conditions – including sinusitis, sore throat, earache, infected insect bites, impetigo, shingles, urinary tract infections (UTIs) – without the need to see a GP first. These changes follow a record funding boost by government to pharmacies of £617 million over 2 years, supported by Community Pharmacy England. A campaign running from 20 October 2025 until 4 January 2026 aims to build awareness of the support community pharmacists can offer to patients in their neighbourhood. It will appear on adverts across TV on Demand services, on radio, in public spaces such as bus shelters, as well as adverts on relevant websites and search engines, online videos and social media. Your local pharmacy can now also provide a free blood pressure check service for anyone over 40, and they are supporting patients who wish to stop smoking through the Smoking Cessation Service. Community pharmacies are also playing an increasing role in NHS vaccination programmes, providing flu and Covid vaccinations to those eligible. Janet Morrison, Chief Executive of Community Pharmacy England, said: “Providing emergency contraception through community pharmacies is a fantastic move for widening access and convenience for patients across the country. “Allowing regular supply of oral contraception from pharmacies has been well received, so building on this to now include emergency contraception is a natural step. “Many pharmacies have been involved in similar local schemes for years, so we’re pleased to see this important new service introduce a consistent offer to women nationally.” Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

2025-03-06

·Firstwordpharma

Senators grill Trump's NIH nominee on vaccines and funding

President Donald Trump's nominee for National Institutes of Health (NIH) director, Jay Bhattacharya, testified on Wednesday before the Senate Committee on Health, Education, Labor and Pensions (HELP) Committee in a confirmation hearing. The Stanford health policy professor, who is known for opposing lockdowns during the COVID-19 pandemic, vowed to reinstate public confidence in science and medicine, while remaining open to scientific dissent.Recent cuts to research funding and vaccine hesitancy were among the main topics discussed, with senators from both sides of the aisle expressing concern. In response to questioning from Bill Cassidy (R-LA) on how vaccine skepticism contributed to the current measles outbreak in Texas, Bhattacharya said he "fully supported" children being vaccinated adding that, "it's a tragedy that a child would die from a vaccine-preventable disease." The NIH nominee said, however, that he would consider funding additional research on childhood vaccines, including on the link (or lack thereof) between vaccines and autism. This prompted frustration from Cassidy, a fellow physician, who lamented that "if we continue to plow the barren ground of something that has already been validated multiple times, that there is not a connection between vaccination and autism, we don't have the money to go after the real thing."On the topic of funding, multiple senators sought reassurance that Bhattacharya would adequately staff the NIH and finance critical research. Patty Murray (D-WA) said she is "deeply concerned about the funding there and the research that has been stopped." Similarly, Susan Collins (R-ME) and Tammy Baldwin (D-WI) pushed Bhattacharya on how he would compensate for the mass firings and funding freezes at NIH, which, they argue, jeopardise the advancement of novel cures and treatments for cancer, Alzheimer's disease and other conditions. When discussing his priorities, Bhattacharya said he planned to take on chronic diseases, including diabetes and obesity. "I don't have the answer on how to solve the obesity crisis," he said. "But I want to make sure the research out there has the support of the NIH."If confirmed, Bhattacharya will work closely with HHS secretary Robert F. Kennedy Jr. who is already making waves by delaying the next US Centers for Disease Control and Prevention vaccine advisory meeting and pledging to "investigate" the childhood vaccine schedule, as well as anti-depressants. The HELP Committee has not yet set a date to vote on Bhattacharya's nomination, which will advance to a vote in the full Senate if approved.

疫苗

2024-12-04

·GlobeNewswire-Health Care

Relmada Therapeutics Reports That Data Monitoring Committee (DMC) Assessment Indicates That the Phase 3 Reliance II Trial is Futile at its Interim Analysis and is Unlikely to Meet the Primary Efficacy Endpoint with Statistical Significance

The DMC did not identify any new safety concerns Relmada to evaluate potential next steps for the REL-1017 program Relmada to continue to focus on the development of REL-P11 for metabolic disease Relmada is well capitalized with approximately $54.1 million in cash and cash equivalents as of September 30, 2024 CORAL GABLES, Fla., Dec. 04, 2024 (GLOBE NEWSWIRE) -- Relmada Therapeutics, Inc. (Nasdaq: RLMD, “Relmada”, “the Company”), a late-stage biotechnology company addressing diseases of the central nervous system (CNS), today announced that the pre-planned interim analysis of Reliance II, conducted by the Independent Data Monitoring Committee (DMC), indicated that the Reliance II Phase 3 study is futile and is unlikely to meet the primary efficacy endpoint with statistical significance. Reliance II is designed to evaluate REL-1017 as an adjunctive treatment for major depressive disorder (MDD), to be used in combination with other approved anti-depressants. No new safety signals were reported. “We are disappointed with the outcome of this interim analysis,” said Sergio Traversa, Chief Executive Officer of Relmada. “Based on these results, Relmada will evaluate the full dataset to determine next steps for the REL-1017 program. The Company will continue to advance the Phase 1 study of REL-P11, an investigational agent for the treatment of metabolic disease, currently in a Phase 1 first-in-human study. We are grateful to the investigative sites and patients who participated in the REL-1017 program." About REL-1017 REL-1017 is a new chemical entity (NCE) and novel NMDA receptor (NMDAR) channel blocker that preferentially targets hyperactive channels while maintaining physiological glutamatergic neurotransmission. About REL-P11 Relmada acquired the development and commercial rights to a novel psilocybin and derivatives program in July of 2021. Psilocybin has neuroplastogen™ effects that have the potential to ameliorate neurodegenerative conditions. Relmada identified the potential to use low-dose psilocybin as a treatment for metabolic diseases and published the data at the American Society for the Study of Liver Disease (AASLD 2023). About Relmada Therapeutics, Inc. Relmada Therapeutics is a late-stage biotechnology company addressing diseases of the central nervous system (CNS) and metabolic disorders. Relmada's experienced and dedicated team is committed to making a difference in the lives of patients and their families. Learn more at www.relmada.com. Forward-Looking Statements The Private Securities Litigation Reform Act of 1995 provides a safe harbor for forward-looking statements made by us or on our behalf. This press release contains statements which constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Any statement that is not historical in nature is a forward-looking statement and may be identified by the use of words and phrases such as "expects”, "anticipates”, "believes”, "will”, "will likely result”, "will continue”, "plans to”, "potential”, "promising”, and similar expressions. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including potential failure of clinical trial results to demonstrate statistically and/or clinically significant evidence of efficacy and/or safety, failure of top-line results to accurately reflect the complete results of the trial, failure of the Reliance-OLS (study 310) to accurately reflect the results of the ongoing Reliance II (study 302) and Relight (study 304) blinded, randomized and controlled studies of REL-1017, failure of the ongoing Phase 1 and planned Phase 2a trials of REL-P11, the Company’s low-dose, modified-release formulation of psilocybin, to be successfully carried out, failure to obtain regulatory approval of REL-1017 for the treatment of major depressive disorder, and the other risk factors described under the heading "Risk Factors" set forth in the Company's reports filed with the SEC from time to time. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Relmada undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Readers are cautioned that it is not possible to predict or identify all the risks, uncertainties and other factors that may affect future results and that the risks described herein should not be a complete list. Investor Contact:Tim McCarthyLifeSci AdvisorsTim@LifeSciAdvisors.com Media Inquiries:Corporate Communicationsmedia@relmada.com

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