Imipramine Pamoate

How hard is it to stop taking antidepressants? If countless Internet posts and a number of scientific studies are to be believed, discontinuing these medications is highly problematic, and doctors often underestimate the difficulties involved. But it is unclear how common discontinuation symptoms actually are. Researchers have now conducted a systematic review and meta-analysis. They conclude that one in three people reports symptoms after discontinuing antidepressant treatment, but half of those symptoms are attributable to negative expectations (the nocebo effect). How hard is it to stop taking antidepressants? If countless Internet posts and a number of scientific studies are to be believed, discontinuing these medications is highly problematic, and doctors often underestimate the difficulties involved. But it is unclear how common discontinuation symptoms actually are. Researchers from Charité -- Universitätsmedizin Berlin and University Hospital Cologne have now conducted a systematic review and meta-analysis. In their article in The Lancet Psychiatry,* they conclude that one in three people reports symptoms after discontinuing antidepressant treatment, but half of those symptoms are attributable to negative expectations (the nocebo effect). According to the formal definition, antidepressants are not habit-forming. Unlike "true" addictive substances, for example, taking them does not cause the body to require higher and higher doses to achieve the same effect. Even so, many patients report symptoms such as dizziness, headache, or insomnia when they stop taking these mood medications. The phenomenon went largely unremarked by researchers for years, but there are now a relatively large number of studies seeking to quantify the extent of discontinuation symptoms. "The results of these studies vary, in some cases widely," says Prof. Christopher Baethge, a researcher at the Department of Psychiatry and Psychotherapy at University Hospital Cologne and the Faculty of Medicine at the University of Cologne. "There has been a great deal of discussion, some of it quite emotional, within the research community and the general public alike in recent years about how prevalent and severe the discontinuation symptoms actually are." A look at prescription figures shows just how relevant this topic is. According to the most recent Arzneiverordnungs-Report, which summarizes data on drug prescriptions, nearly 1.8 billion daily doses of antidepressants were prescribed in Germany in 2022. Comprehensive meta-analysis brings clarity To answer that question more reliably than before, a team led by Christopher Baethge and Dr. Jonathan Henssler, head of the Evidence-Based Mental Health research group at the Department of Psychiatry and Neurosciences at Charité, conducted a systematic review of existing studies and re-analyzed them in what is known as a meta-analysis. As the first study of its kind, it provides the soundest assessment to date of the consequences of stopping antidepressant treatment. "Our analysis shows that on average, one in three people will experience symptoms after stopping antidepressant treatment," Henssler says. "However, only half of these symptoms are in fact attributable to the drug itself." For their paper, the researchers reviewed more than 6,000 studies. They then selected 79 of them and re-analyzed the results of those trials using statistical methods. In the end, they analyzed data on about 21,000 people, who had received either an antidepressant or a placebo and then been surveyed regarding the prevalence of discontinuation symptoms. Some 31 percent of the patients treated with an active drug reported discontinuation symptoms, but so did 17 percent of those who had received a placebo alone. One in six or seven people experiences true discontinuation symptoms "Drug effects can be ruled out in the placebo group, which means the symptoms either arose by chance, independently of the treatment, or they are the product of the nocebo effect," Henssler explains. The nocebo effect is often considered the mirror image of the placebo effect. It explains the observation that inactive treatments can be associated with "side effects." These effects are triggered purely by the expectation that the treatment that people think they are receiving will have negative effects. "When we take non-specific symptoms and the effect of expectations into account, about one in six or seven people is affected by discontinuation symptoms that occur as an actual consequence of antidepressant medication," Henssler says, summing up the study's results. "In most cases, the symptoms are mild. The vast majority of those affected will be able to discontinue antidepressants without relevant symptoms. This means that in most cases, there is no need for a lengthy or gradual tapering process." Severe symptoms are rare The study found that severe discontinuation symptoms are experienced by one in 35 people, or nearly three percent of those affected. These kinds of symptoms were more common after discontinuing treatment with the drugs imipramine, paroxetine, venlafaxine, and desvenlafaxine. There was not yet enough information on hand for the researchers to assess the situation for a number of widely used antidepressants. As Baethge points out, "It's important for all people wishing to discontinue treatment with antidepressants to be monitored and counseled by healthcare professionals and to receive individual support in the case of withdrawal symptoms. Joint decision-making between the patient and prescriber even before a course of treatment begins is the foundation of good treatment. We hope our data will support patients and healthcare professionals and help alleviate some of the uncertainty surrounding these issues today." About the study The 79 studies considered in the meta-analysis included both randomized placebo-controlled trials and observational studies conducted without a control group. Of the 21,002 patients involved in the studies, 16,532 had received an antidepressant, and 4,470 a placebo. In addition to the researchers from Charité and University Hospital Cologne, researchers at the Medical Center -- University of Freiburg and University Hospital Carl Gustav Carus, in Dresden, were involved in the meta-analysis.

Novel compounds protected under Enveric’s intellectual property portfolio provide potential licensing opportunities and non-dilutive revenue streams. CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Enveric Biosciences (NASDAQ: ENVB) (“Enveric” or the “Company”), a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders, today announced the discovery of multiple, promising novel compounds sourced using the company’s Psybrary™ platform and proprietary computational chemistry and artificial intelligence (AI) drug-discovery system (PsyAI™). The novel compounds span seven distinct molecule classes totaling at least 57 unique product opportunities, all of which are protected by Enveric’s expansive intellectual property portfolio and represent potential out-licensing opportunities and non-dilutive revenue streams for the Company. Together, the novel and distinct molecule classes broaden and deepen Enveric’s library of assets targeting difficult-to-address mental health disorders, adding to its lead candidate EB-003, a first-in-class neuroplastogen designed to eliminate hallucinations, and EB-002, formerly EB-373, a next generation synthetic prodrug of the active metabolite, psilocin. “Our ability to identify EB-003 and EB-002 as our lead drug candidates was the result of an extensive process in which our research team analyzed more than one thousand compounds spanning numerous classes of molecules, utilizing our proprietary PsyAI and Psybrary platforms,” said Joseph Tucker, Ph.D., Director and CEO of Enveric. “As a result, Enveric now possesses what we believe to be one of the most diverse portfolios of potential drug molecules for the treatment of key, underserved mental health and neurological disorders. Our dedicated approach to protecting our discoveries should enable us to generate significant near- and long-term value for our shareholders via potential partnering and/or licensing agreements.” The novel compounds span seven diverse molecule classes and subclasses, including: Novel Serotonin-Norepinephrine-Dopamine Reuptake Inhibitors (SNDRI) Also known as triple reuptake inhibitors (TRIs), SNDRIs are an emerging class of medications designed to treat severe depression and anxiety disorders. Enveric SNDRI compounds show strong binding to serotonin transporter (SERT), norepinephrine transporter (NET) and dopamine transporter (DAT). Enveric SNDRI compounds also demonstrate distinct additional serotonin receptor binding profiles that bear similarities to those of the antidepressant Nefazodone and the anxiolytic Buspirone. Non-selective Serotonin Reuptake Inhibitor (NSRI) Enveric NSRI compounds show strong binding to SERT, as well as to the 5-HT1A receptor, known to be a therapeutically valuable target. Certain of Enveric’s NSRIs demonstrate additional binding to various serotonin and dopamine family receptors, with binding profiles similar to the antidepressant Vortioxetine and the atypical antipsychotic Aripiprazole. Novel MDMA Derivatives (EMD) Series Twenty novel MDMA derivatives are separated into three subgroups: Strong 5-HT2A receptor binding, Weak 5-HT2A binding, and No 5-HT2A receptor binding. Current literature indicates agonism of the 5-HT2A receptor is linked to hallucination in humans and also to the induction of neuroplasticity. Each subgroup of Enveric’s novel MDMA derivatives demonstrates unique and expanded receptor binding activity targeting adrenergic and/or dopaminergic receptors as well as epinephrine/norepinephrine family receptors. Some of the resulting receptor binding profiles are similar to the anxiolytic Buspirone, the antiepileptic Fenfluramine, the ADHD drug Guanfacine, and the atypical antipsychotic Aripiprazole. Bifunctional Psilocin Prodrugs (BPP) BPPs are readily absorbed, detectable in plasma, and converted to therapeutically relevant levels of plasma psilocin, with demonstrated lower Head Twitch Response (HTR) relative to psilocybin in mice; HTR is reported in the literature to be a predictive indicator for hallucination in humans. Each BPP parent prodrug demonstrates its own unique binding pro serotonin 5-HT1A receptor, 5-HT1B receptor and SERT, with similarities to anxiolytics Buspirone, antidepressant/anxiolytic Flesinoxan, and the antidepressant Paroxetine. Novel Psilocin Prodrug (NPP) Series NPPs are designed to be metabolized to release therapeutic levels of systemic psilocin at varying rates, providing treatment regimen optionality. Included in this series are four compounds that can be converted upon direct intravenous injection to psilocin: potentially bypassing the need for first-pass metabolism, making them amenable to non-oral forms of administration (e.g. intranasal, sublingual, buccal). Melatonin-Receptor Agonist (MRA) Series Melatonin, a natural indolamine, is essential for regulating circadian rhythm in mammals and is often used in to treat a variety of sleep disorders. Enveric MRA compounds demonstrate strong binding to the MT1 Melatonin receptor with some being highly selective for MT1 while others demonstrate expanded target binding profiles similar to the antidepressants Agomelatine, Vortioxetine, Imipramine, and Trazodone. Neuroplastogenic Antidepressant (NAD-01) Designed to induce neuroplasticity and promote long-term therapeutic benefit in patients suffering from severe depressive mood disorders. Demonstrates neuroplastogenic activity comparable to known 5-HT2A receptor agonist N,N-Dimethyltryptamine (DMT). Demonstrates weak 5-HT2A receptor binding affinity and activation. Produces lower Head Twitch Response relative to psilocin and DMT, while promoting recovery of sucrose preference (SP) in stressed mice - an accepted model for evaluation of antidepressant activity. For more information about Enveric’s novel preclinical compounds spanning multiple, distinct classes of molecules, please visit: . About Enveric Biosciences Enveric Biosciences (NASDAQ: ENVB) is a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders. Leveraging its unique discovery and development platform, Psybrary™, Enveric has created a robust intellectual property portfolio of New Chemical Entities for specific mental health indications. Enveric’s lead program, EB-003, is a first-in-class approach to the treatment of difficult-to-address mental health disorders designed to promote neuroplasticity without inducing hallucinations in the patient. Enveric is also developing EB-002, formerly EB-373, a next generation synthetic prodrug of the active metabolite, psilocin, being studied as a treatment of psychiatric disorders. Enveric is headquartered in Naples, FL with offices in Cambridge, MA and Calgary, AB Canada. For more information, please visit . Forward-Looking Statements This press release contains forward-looking statements and forward-looking information within the meaning of applicable securities laws. These statements relate to future events or future performance. All statements other than statements of historical fact may be forward-looking statements or information. Generally, forward-looking statements and information may be identified by the use of forward-looking terminology such as “plans,” “expects” or “does not expect,” “proposed,” “is expected,” “budgets,” “scheduled,” “estimates,” “forecasts,” “intends,” “anticipates” or “does not anticipate,” or “believes,” or variations of such words and phrases, or by the use of words or phrases which state that certain actions, events or results may, could, should, would, or might occur or be achieved. Forward-looking statements may include historical statements and statements regarding beliefs, plans, expectations, or intentions regarding the future and are based on the beliefs of management as well as assumptions made by and information currently available to management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors, including, but not limited to, the ability of Enveric to: carry out successful clinical programs in Australia; achieve the value creation contemplated by technical developments; avoid delays in planned clinical trials; establish that potential products are efficacious or safe in preclinical or clinical trials; establish or maintain collaborations for the development of therapeutic candidates; obtain appropriate or necessary governmental approvals to market potential products; obtain future funding for product development and working capital on commercially reasonable terms; scale-up manufacture of product candidates; respond to changes in the size and nature of competitors; hire and retain key executives and scientists; secure and enforce legal rights related to Enveric’s products, including patent protection; identify and pursue alternative routes to capture value from its research and development pipeline assets; continue as a going concern; and manage its future growth effectively. A discussion of these and other factors, including risks and uncertainties with respect to Enveric, is set forth in Enveric’s filings with the Securities and Exchange Commission, including Enveric’s Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q. Enveric disclaims any intention or obligation to revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.