Citalopram Hydrochloride

If four full 737s were crashing daily resulting in total loss of life, there would be a public outcry and immediate governmental intervention. Yet, we lose an equivalent number of people daily — 275,000 American lives annually — to adverse drug events (ADEs). This public health crisis largely goes unnoticed because it happens to one mother, one son, one sister, and one friend at a time in homes, clinics, emergency rooms, nursing homes, and hospitals. Outdated surveillance and reporting systems mean many more ADEs go unrecorded. Most ADEs occur when medications are administered and taken correctly, contrary to the popular belief that this is most frequently due to non-adherence. The impact is worse for women, who are twice as likely to experience ADEs, and for non-White patients. This is because clinical trials for the generic drugs we primarily prescribe were conducted years ago and mostly included only White males of European ancestry. While some medication harm may be unavoidable, studies indicate that half or more can be prevented by prioritizing education, equitable healthcare access, and technology, which will require legislative action. The growing public health crisis Sponsored Post Get Ready for HLTH 2024: A Preview Guide HLTH 2024, scheduled for October 20-23 at the Venetian Expo Center in Las Vegas, will highlight new programming, a physicians roundtable, generative AI, the shifting landscapes of telemedicine, retail health, women's health, and lots more. By Stephanie Baum In 2016, the last time it was measured, we spent $528 billion on non-optimized medication, a staggering figure that exceeds the cost of the drugs themselves or any major chronic disease. The more medications a patient takes, the higher the risk of ADEs. Currently, over 40 million patients take five or more medications daily. With the “silver tsunami” of baby boomers aging into Medicare, this number is expected to double by 2040. The time to act is now. Despite investment in precision medicine, pharmacogenomics (PGx) testing is still underutilized as a tool for reducing avoidable medication harm. PGx testing helps determine which drugs and doses are likely to be safe and/or effective based on each patient’s genetic makeup. It is precision medicine for medications. Unlike other genetic variations that are usually uncommon, PGx variations occur in over 99% of patients. A single, comprehensive, multi-gene test can help maximize the safety and efficacy of many commonly prescribed medications used in mental health, pain management, cardiovascular care, cancer care, and more. Drug-gene interactions are very similar to drug-drug interactions – in fact, the FDA has stated in drug development guidance that they are similar in scope and should therefore receive similar attention. The key differentiator is unlike drugs, genetics cannot be altered. Consider the 1,300 patients that die each year, not from cancer, but from the fluorouracil or capecitabine treatment itself. For 5-7% of patients with DPYD PGx variants, standard doses of these medications can be toxic with a 25.6 times increased risk of treatment related death. Or, consider the 8% of patients with certain PGx variations impacting citalopram and escitalopram metabolism that are 34.3% more likely to become suicide victims because the drugs are processed out too quickly to provide treatment benefit or so slowly that they increase adverse effects leading to treatment discontinuation. Perhaps also consider the patients who continue to receive clopidogrel without PGx testing despite an FDA black box, first added in 2010, warning that patients with certain PGx variants are more likely to have another heart attack or stroke. The promise of PGx testing Biomarker testing, including PGx testing, can help turn this tide. Numerous studies have confirmed that optimizing prescribing with PGx testing reduces emergency room visits, hospitalizations, and healthcare costs. A large trial in several European countries across various specialties and care settings showed a 30% reduction in clinically significant adverse drug events in just 12 weeks. A recent meta-analysis in adult cancer patients showed a 53% reduction in significant adverse events with use of PGx testing. And despite the lack of widespread adoption, medical liability risks are increasing when evidence-based PGx testing is not discussed with and offered to patients. So why isn’t it standard of care? Numerous hurdles stand in the way of PGx testing becoming the standard of care, including: Inconsistent insurance coverage: A significant barrier to equitable access and adoption of biomarker testing, including PGx testing, is inconsistent insurance coverage that has not kept pace with professional guidelines and advances in the evidence. This has led to further socioeconomic, racial, and ethnic disparities in accessing quality care. Lack of education and clinical decision support: Both provider and patient education and prioritization of integrated clinical decision support are necessary to realize the benefits of genomic medicine, including PGx-guided medication management. Pharmacists’ lack of recognition as healthcare providers: Although many states recognize pharmacists as healthcare providers, they are not yet acknowledged as providers at the federal level. This lack of federal recognition hinders reimbursement for pharmacists, despite their provision of numerous and essential direct-care patient services that align with their training, including PGx-guided medication management. Support biomarker legislation and prioritize PGx educationTo address insurance coverage barriers, biomarker legislation has been enacted in sixteen states including Arizona, California, Georgia, Illinois, Maryland, Texas, and New York, and introduced in eleven others. The National College of Insurance Legislators (NCOIL) endorsed model biomarker legislation in the summer of 2023, setting the stage for expected nationwide adoption. Typically, this legislation requires state insurance providers, including Medicaid and commercial payers, to cover tests that guide treatment decisions based on medical and scientific evidence including testing covered by CMS NCDs, Medicare Administrative Contractor LCDS, or nationally recognized clinical practice guidelines and consensus statements. Medicare LCDs have covered certain evidence-based PGx testing since 2020.Clinicians must prioritize educating themselves about PGx testing and incorporate it into their practice to improve patient safety and care. Free resources can be found at NIH Inter-Society Coordinating Committee for Practitioner Education in Genomics (ISCC-PEG). Healthcare professionals in states that have not enacted biomarker legislation can learn how to support state efforts at ACS CAN. Other legislative actions and advocacy efforts to improve drug safety and reduce ADEs are also in the works. They include: Right Drug Dose Now Act of 2024 – You can urge your congressional representatives to support this act – learn more and sign support at Fourth Cause. Reintroduced by Swalwell and Crenshaw at the end of March, this bipartisan act would: Require an assessment and update of the National Action Plan for Adverse Drug Event Prevention; Create a healthcare provider educational campaign on preventing adverse drug events, in part by using evidence-based PGx information. Incentivize updates to electronic health record systems to ensure that healthcare providers are alerted to interactions between medications and genes when making prescribing decisions; Enhance reporting systems that would assist with the reporting of PGx-associated adverse drug events A second associated bill authorizes sustained funding for PGx implementation research and guideline development. Pharmacy and Medically Underserved Areas Enhancement Act – The bill would enable pharmacists to deliver Medicare Part B services that are already authorized by their respective state laws. Learn more at ASHP. Sponsored Post What Healthcare Can Learn from Costco The path forward is clear: employers must evaluate their health plan the same way they do their Saturday shopping excursion. By Jeff Bak, Imagine360 CEO and President The Hippocratic oath of “first do no harm” can’t stop with direct patient care; the healthcare industry and its key stakeholders must address persistent public health problems systematically. We have the tools to reduce medication harm by half or more; it is long past time to make this a public health priority. Common-sense legislation needs to be passed to ensure we move beyond an outdated system for medication management and safety that is no longer serving providers or the patients they care for. Editor’s note: The author on the PGx committee of the NIH Inter-Society Coordinating Committee for Practitioner Education in Genomics (ISCC-PEG), a member of the PGx workgroup for the American Cancer Society Cancer Action Network (ACS CAN) and serves on the steering committee for STRIPE, the FDA collaborative community for PGx.

iStock/ bestdesigns After the FDA declined to approve Lykos Therapeutics’ MDMA-assisted therapy for post-traumatic stress disorder, companies are pivoting away from or delaying similar therapeutics targeting the psychiatric disease. Once confined to the party scene, midomafetamine, or MDMA (colloquially known as ecstasy), has garnered recent attention for its therapeutic potential. The Schedule I drug has shown particular promise in treating post-traumatic stress disorder (PTSD), a serious mental illness with notoriously few treatment options. The psychedelic treatment space was struck a blow, however, when the FDA rejected Lykos Therapeutics’ MDMA-assisted therapy for PTSD in August. In its Complete Response Letter, the agency said the application “could not be approved based on data submitted to date” and requested that Lykos conduct an additional Phase III trial to glean more information on the drug’s safety and efficacy. The sentiment appears to be that the FDA’s issues were more reflective of Lykos’ new drug application (NDA) than MDMA on the whole. “I think the setback Lykos had mostly reflects on Lykos’ [trial design] and not so much on MDMA,” Matthew Baggott, co-founder and CEO of psychedelics-focused Tactogen, told BioSpace , adding that in addition to data deficiencies, there may have been “extra-scientific” factors, including political pressure. Still, some psychedelic drug developers are reassessing their pipelines and prioritizing other assets, taking a wait-and-see approach to MDMA while working to make the drugs safer. Tactogen, for one, is reexamining its strategy. “The fact that Lykos didn’t get their NDA approved on this cycle means that we are seriously considering prioritizing our novel compounds and waiting to move forward with our MDMA product,” Baggott said. Tactogen’s pipeline includes a number of preclinical molecules that Baggott said he believes will be superior to MDMA. Fellow psychedelic drug developer atai Life Sciences is prioritizing its MDMA-based asset, EMP-01, in social anxiety disorder, initiating a Phase II trial in late 2024. For PTSD, the company will “see how things work out with Lykos,” co-CEO Srinivas Rao told BioSpace. The Lykos decision is “overall good for companies like Tactogen in that we’ve continued to get a clearer and cleaner roadmap from the FDA as to what they want,” Baggott said, noting recent FDA guidance, the documents from the Lykos adcomm and the public statements that followed that meeting. Potential for Abuse? The FDA issued a guidance document in June 2023 for psychedelic drug trials, acknowledging that these compounds carry unique challenges for study design. Among the safety-related concerns noted are abuse potential and alterations to consciousness and behavior that can last for several hours. Baggott said the biggest perceived challenge to MDMA’s approval is the concept of abuse liability. Therapeutic outcomes such as feelings of self-compassion or emotional positivity are considered warning signs for possible abuse, he said. Some of these effects are “easily mapped” using the medical dictionary for regulatory activities (MedDRA), Baggott added, but other experiences patients may have while on MDMA are more difficult to assign standardized medical terminology. Capturing these events in a way that is acceptable to the FDA will be “really important.” Other experts have argued that MDMA is not frequently abused in recreational settings. Howard Kornfeld, a medical director at Recovery Without Walls who worked with patients treated with MDMA in the 1980s before it was a scheduled drug, said it is rarely abused. He clarified that in “unusual situations,” MDMA can be taken in the wrong dose, leading to bad outcomes. Lykos’ regimen requires patients to undergo three sessions, completely supervised, Kornfeld noted. “People aren’t going to get addicted from these three sessions,” he said, adding that despite concerns over patients “getting a taste” of the drug and seeking it out on the streets, “we really haven’t seen that in 40 years of real-world data.” Improving the Safety Profile Amidst this debate, Tactogen is working to improve the safety pro MDMA through fixed dose combinations in hopes of decreasing side effects like difficulty concentrating and mood instability seen in some participants in the days after use. The company also hopes to improve tolerability with its program combining MDMA with citalopram, a selective serotonin reuptake inhibitor (SSRI) used to treat depression, for PTSD. Baggott anticipates beginning Phase II trials with the combo in 2025. Meanwhile, with EMP-01, atai is hoping to improve the safety of MDMA by focusing on one of its two enantiomers. MDMA is an equal mixture of both (S)-MDMA and (R)-MDMA. The (S) enantiomer is very much like a stimulant, Rao explained, with so-called entactogenic properties that induce the external, social effects of MDMA. (R)-MDMA, on the other hand, has more exergonic activity thought to contribute to the psychedelic effects, he said. With the stimulant effects of the (S) enantiomer posing potential cardiovascular risks for PTSD patients, atai used only (R)-MDMA in its candidate to potentially improve the therapeutic index of traditional MDMA. “What we found is that the compound was very different than anticipated, and in a good way,” Rao said. In a traditional MDMA trial, a common dose would be 150 mg, which would include 75 mg of (R)-MDMA and 75 mg of (S)-MDMA. Atai’s molecule comprises 225 mg of (R)-MDMA. In a Phase I trial, it elicited psychedelic effects beyond hallucination, enabling introspection and affecting patients’ ability to see their lives differently, Rao said. EMP-01 was found to be well-tolerated in healthy volunteers. High Unmet Need Prior to the Lykos decision, Kornfeld sent a letter to the FDA advocating for the MDMA-based therapy to be approved, and said he was disappointed when it was rejected. Kornfeld said the delay is a “loss of opportunity” to lower the death rate from PTSD-related suicides in America, adding that concern is especially high for veterans. According to the U.S. Department of Veterans Affairs, seven out of every 100 veterans will have PTSD. In 2021 , there were over 17 veteran suicides per day, per the Office of Mental Health and Suicide Prevention. Around the world, other countries have made a different decision regarding MDMA as a therapeutic. In 2023, Australia’s government approved the use of MDMA for PTSD, as long as it is administered as an assisted therapy by an authorized prescriber. And on the heels of the negative Lykos FDA adcomm vote, a Dutch panel recommended MDMA to its government for the treatment of PTSD. “The government must act expeditiously to enable the therapeutic use of MDMA,” a statement from the state commission said. One thing is certain: unmet need in PTSD is high, Kornfeld said. “There has not been a new drug approved for PTSD for more than a decade. We basically have an epidemic of PTSD. I’m hoping that MDMA can get approval sooner rather than later.”