Podcasts about Olanzapine

First, a disease befell us, and then She cast her spell (chant with us), ABRACADABRA AMOR-OO-NA-NA… Vanity Project put their paws up one more time for Lady Gaga's seventh studio album, Mayhem. This time we are joined by a very special guest, longtime Little Monster and boyfriend of the pod Caleb Bunselmeyer.Together, we come home to Mother Monster and cast our collective memory to the music that soundtracked our most shameful moments. We speculate on the effect of third fiancé Michael Polansky, of the side effects of anti-psychotic Olanzapine, and of listening to Gaga music alone. Truthfully, the lie of it all is much more honest…

Send Me a Message! In this episode of The Dysregulated Podcast, I explore the vital role Seroquel plays in my ability to get a good night's sleep and how its absence leaves me battling through the day. Sleep deprivation exacerbates the negative ruminations that seem to take centre stage of my psyche, and today, they've been particularly focused on my inner workaholic—the sub-part of me constantly pushing to apply for new jobs and to (hopefully) improve my life! That is one part of me that doesn't slow down, even if the self has! Join me as I do my best to explain the challenges of sleeplessness, self-criticism, and the weight of unrelenting expectations, all before the Seroquel kicks in and I finally get some rest!-Follow my journey living with mental illness and the hard-fought lessons learned along the way. Lived experience is the driving force of this podcast, and through this lens, my stories are told. This is a raw, honest, and authentic account of how multiple psychological disorders have shaped my past and continue to influence my future.Support the showTo support the show, CLICK HEREYou can follow me on Instagram: @elliot.t.waters

Dr. Larry Wang will be hosting todays episode with a very special guest. . . another Dr. Larry Wang? . . . Bipolar depression being treated with an antidepressant? Welcome to the multiverse.

Welcome back to our antipsychotic series. Today, we will be discussing Olanzapine, brand-name, Zyprexa.

Very few people are willing and/or able to share and describe their descent into psychosis— in part because memory formation and consolidation are so impaired during episodes of psychosis…..and also because there is often so much fear and shame tied up in the experience of losing one's mind. Here Dr. H's  patient Corben describes his very early onset illness, how it started with years of depression,  then shifted into profound alienation and increasingly frightening psychosis, and finally into stability and recovery.BFTA on IG @backfromtheabysspodcasthttps://www.instagram.com/backfromtheabysspodcast/BFTA/ Dr. Hhttps://www.craigheacockmd.com/podcast-page/

On this episode of the Real Life Pharmacology podcast, we cover 5 more medications in the top 200. Metronidazole is an antibiotic for infection. One of the most common complaints from patients involves reporting of a metallic taste in the mouth. Levetiracetam is an anti-seizure medication. Sedation, dizziness, and other adverse effects of the central nervous system are the most common complications. Colchicine is a gout medication. The most memorable side effect associated with this medication is diarrhea. Olanzapine is an antipsychotic. Olanzapine carries a higher risk for metabolic syndrome compared to other antipsychotics. Dutasteride is a 5 alpha-reductase inhibitor that is indicated for the treatment of BPH. If you are looking for all of our study materials and Amazon books, check them out at Meded101.com/store!

A mixed bag of Phase III results for using olanzapine with moderately emegotenic chemotherapy (MEC). Inui, et al: https://doi.org/10.1200/JCO.24.00278 Ostwal, et al: doi:10.1001/jamanetworkopen.2024.26076

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In this episode, we examine whether first-trimester exposure to the antipsychotic olanzapine increases the risk of major fetal malformations. Does stopping medication abruptly also carry risks? Faculty: David Rosenberg, M.D. Host: Richard Seeber, M.D. Learn more about our membership here Earn 0.5 CMEs: CAP Smart Takes Vol. 14 Risk of Major Malformations Following First-Trimester Exposure to Olanzapine

Health officials are warning a shortage of anti-psychotic drug - olanzapine - could cause relapses for people with schizophrenia symptoms. Supply of the injected medication is already low, and a shipment didn't arrive last month. Royal College of Psychiatrists New Zealand chair, Hiran Thabrew, says it's critical for people to get their regular medication, or a substitute. "What might happen is that people might experience a deterioration in their mental state, they might notice symptoms of psychosis start to occur and people around them might notice their behaviour changing." LISTEN ABOVESee omnystudio.com/listener for privacy information.

In this episode, we explore whether the olanzapine–samidorphan combination helps with psychosis while halting weight gain. We also look into the cost vs benefit of the combination as well as the metabolic side effects. Faculty: James Phelps, M.D. Host: Richard Seeber, M.D. Learn more about our membership here Earn 0.5 CMEs: Quick Take Vol. 51 Comparative Efficacy, Safety, and Acceptability of Pimavanserin and Other Atypical Antipsychotics for Parkinson's Disease Psychosis: Systematic Review and Network Meta-Analysis

Dr. Mindy answers questions about fingernails, fasting, flu shots, pink eye, blood clots, eating too many green beans, Colitis, knugget knots, hurt necks, leaky guts, skin tags, collagen supplements, Olanzapine, postpartum, Albuterol disposal, migraines, going to the bathroom a lot and a cheaper Mounjaro.See omnystudio.com/listener for privacy information.

The Frontier Psychiatrist's newsletter? It is what you are reading. It's a health-themed publication written by Owen Scott Muir, M.D. This is a brief detour from my recent series on medications, many of which have a critical slant. Those include Risperidone, Depakote, Geodon, Ambien, Prozac, Xanax, Klonopin, Lurasidone, Olanzapine, Zulranolone, Benzos, Caffeine, Semeglutide, Lamotrigine, Cocaine, Xylazine, Lithium, dextromethorphan/bupropion and Adderall, etc. I write this all by myself every day. Consider subscribing. (the paywall starts 5 weeks back, and there are 360something articles back there). It makes a horrible or awesome gift, depending on your friend circle. I also get paid more money by Amazon if my readers buy stuff now, like, for example, my favorite book about mental illness—or this tea I drink daily. I also encourage you to send me this coffee maker— or, more realistically, to anyone else.Today, I address what happens when schizophrenia is not treated, even if it is. It has high morbidity and mortality, a problem that medications address. Effectively. Not without costs, but the best data suggests treatment is better than no treatment for most people.I'm going to cut to the chase briefly, and if you or a family member want to read a great book on treatment with antipsychotic medicine, I'd recommend this one. Jeff Leiberman, M.D., has been …controversial… of late. However, there is no denying his role in understanding schizophrenia and its treatment, and his book on the topic is worth a read or listen, called a Malady of the Mind.Psychotic. We use the word commonly in chit-chat to denote something is bad. Unreasonable. Wrong. Deranged. Nothing is beguiling about the word. It is a thing to deny in oneself— “I am not psychotic!”Understanding PsychosisSome people don't get that luxury. Some people are honest-to-goodness psychotic. Most of us do not know what that means. Some of us do, and some smaller portions are blessed with the ability to spend time on both sides of that psychotic equation. I will define the term:Psychosis refers to a collection of symptoms that affect the mind, where there has been some loss of contact with reality. During an episode of psychosis, a person's thoughts and perceptions are disrupted and they may have difficulty recognizing what is real and what is not. The most common illness we associate with psychosis is schizophrenia. Psychosis can occur with depression, bipolar disorder, and other maladies. Depression and mania are mood states; we refer to these mixed with psychotic symptoms as affective disorders in psychiatry. A brief grammar note, brought to you by Grammarly, a tool I use and—sadly—am not paid to promote:Is affective just another word for effective? Are the two words similar and entangled in the way the verbs affect and effect are? No, affective is not just another word for effective. And affective and effective are not derived from the verbs affect and effect. They come from the nouns affect and effect.There is a difference in the literature—and in the lives of patients—when it comes to illnesses that have affective psychosis and non-affective psychosis. Much of the anti-psychiatry crowd focuses on affective disorders and argues about the side effects of those treatments. Less attention is paid to non-affective psychosis because It's not as compelling an argument. These are challenging illnesses either way and are associated with significant morbidity—impairments in life—and mortality—early death.“Uncured of Worse”: 1937.As far back as 1937, authors noted the grim prospects in the long-term course of schizophrenia (in this context, I'm referring to largely “non-affective psychosis” —where the delusions or hallucinations are not tied to mood episodes):Of the 100 cases, 66% were uncured or worse after the lapse of 6-10 years, with persisting process symptoms or in a defective state after the course had run; 13% were improved, 4% were cured with defects, and 17% were completely cured. “The Prognosis is Poor”: 2010By 2010, with decades of more data, the conclusion was much the same—schizophrenia sucks, even compared to other admittedly bad illnesses:Our 26-year longitudinal study and other longitudinal studies confirm older views that outcome for schizophrenia, while showing some variation for different schizophrenia patients, is still significantly poorer than that for other psychiatric disorders.A large NIMH follow-up study with 2 to 10 years of time following patients from a first episode that required hospitalization demonstrated:The sample showed substantial functional impairment and levels of symptoms, with only about 20% of the sample demonstrating a good outcome…The “not-good” outcomes looked like this:78% of the sample suffered a relapse, 38% attempted suicide and 24% had episodes of major affective illness.Beyond Psychiatric Problems?We tend to focus on the role of bad psychiatric outcomes as psychiatrists. Still, the medical outcomes are similarly troubling, including high smoking rates, metabolic syndrome, heart disease, HIV, Hepatitis C, and other medical illnesses. Overall, this leads to an extremely disheartening finding: having schizophrenia is an illness that takes a tremendous toll on the individual and their family and leads to early death and disability at unacceptably high rates:Persons with schizophrenia have an exceptionally short life expectancy. High mortality is found in all age groups, resulting in a life expectancy of approximately 20 years below that of the general population. Evidence suggests that persons with schizophrenia may not have seen the same improvement in life expectancy as the general population during the past decades. Thus, the mortality gap not only persists but may actually have increased.Comparisons are useful, and if we look at HIV after the introduction of HAART (Highly Active Anti-Retroviral Therapy), we find:HIV-related mortality decreased from 6.5 to 1.3 per 100,000 population (80% decrease, p = 0.0115). New HIV diagnoses declined from 702 to 238 cases (66% decrease; p = 0.0004) with a consequent estimated decline in HIV incident cases from 632 to 368 cases per year (42% decrease; p = 0.0003).And if we compare that to schizophrenia, in the largest meta-analysis I could find, we find:The mortality risk for patients with schizophrenia was 1249 per 100 000 … (95% CI, 1029-1469)Psychosis is Bad Compared to Other Bad ThingsThe mortality from schizophrenia is 19,215% higher than from pre-HAART HIV infection and 96,076% higher than from HIV with HAART treatment. If you had to choose between HIV and schizophrenia, HIV is safer—with or without treatment.To make the point even more clearly, even having a car crash only has a 0.77% fatality rate, or 770/100,000.If you had to choose between a car crash and schizophrenia, the car crash is safer.Those outcomes are not good enough. Schizophrenia is impairing and dangerous to your life, especially if untreated. Other psychiatric illnesses are also. Psychiatric medications can modify this risk to your life in the right direction, even with those risks. Tapering them, as we saw in the RADAR trial (lead-authored by a critical psychiatrist, published in the Lancet just this week), doesn't make it better:At 2-year follow-up, a gradual, supported process of antipsychotic dose reduction had no effect on social functioning.And, further, made it worse:here were 93 serious adverse events in the reduction group affecting 49 individuals, mainly comprising admission for a mental health relapse, and 64 in the maintenance group, relating to 29 individuals.It includes twice as many deaths. In a research study, this is a huge deal. The way to look at this is the probability of relapsing is bad, and it's statistically more likely and with more than double likelihood if you were randomized to a taper protocol.Antipsychotic Medication Saves Lives. It has Burdens. These Choices are Difficult. We need to do better, but the haters are incorrect. We have done better than nothing, even with imperfect tools, even when examined by those who have an axe to grind with those very tools. Treatment of schizophrenia saves lives.Stay Humble,Faced with Suffering, and Carry On—Owen Scott Muir, M.D. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit thefrontierpsychiatrists.substack.com/subscribe

My favorite opening line of an academic article (this week) follows:Mental illnesses are prevalent, cause great suffering, and are burdensome to society.Welcome to the Frontier Psychiatrists. It's a newsletter that I write all by myself. I'm doing a series on medications, largely (but not entirely) in psychiatry. I'm a child and adult psychiatrist, and I still see patients. I've also been a patient since I was 16 years old. Please consider subscribing and sharing widely.The first antipsychotic introduced after clozapine would be a big deal—especially if it didn't cause life-threatening side effects. Risperidone was first developed by the Johnson & Johnson subsidiary Janssen-Cilag between 1988 and 1992 and was first approved by the FDA in 1994. It's one of the very few drugs with data for bipolar disorder that I, personally, have never been prescribed.Risperidone—Risperdal as a trade name—was ready to be a huge hit.It was presented as very atypical—this was the post-clozapine branding of choice. The “second generation” label was added years later. I have a confession to make. After residency, when the attending doctors told me, as a trainee, what to prescribe, I never prescribed risperidone ever again. I think this compound—and paliperidone, the metabolite— still has an important role in managing schizophrenia and bipolar disorder. There are more formulations of long-acting injectable risperidone and related compounds than I can remember. I think those are going to be useful drugs for a long time. Oral risperidone? Nope.Clozapine was an exciting drug. No horrible motor side effects? (Plausibly) More effective? It was better than every drug that came before. It had this pesky adverse effect that could lead to death called agranulocytosis, which I addressed in my first research paper in 2011. We needed more drugs that were this atypical!We—the field of psychiatry, at least— needed things that were not gonna kill you abruptly, in a terrifying manner, like clozapine had the rare potential to do. But we didn't want more of the same old antipsychotics. After Psychiatry got a taste of not having to explain permanent tardive dyskinesia as a likely side effect of antipsychotic medication, we wanted to keep doing that. Editors note: It is still a side effect of all non-clozapine antipsychotics, and we should never have let our guard down.Risperidone was the first antipsychotic that came to market after clozapine rocked the world of psychiatry by being better. Risperidone is similar, and they even use the accidental branding of clozapine— “atypical”—for this medication. The Food and Drug Administration (FDA)-approved indications for oral risperidone (tablets, oral solution, and M-TABs) include the treatment of:* schizophrenia (in adults and children aged 13 and up), * bipolar I acute manic or mixed episodes as monotherapy (in adults and children aged 10 and up), * bipolar I acute manic or mixed episodes adjunctive with lithium or valproate (in adults)* autism-associated irritability (in children aged 5 and up). Also, the long-acting risperidone injection has been approved for the use of schizophrenia and maintenance of bipolar disorder (as monotherapy or adjunctive to valproate or lithium) in adults.The “mechanism of action” of all of the drugs that have efficacy in psychosis was presumed to be dopamine D2 receptor blockade, a mechanism shared with all of the prior medication from Thorazine (chlorpromazine) through Haldol (haloperidol). The assumption—which clozapine disproved—was motor side effects were required for the drug's efficacy in psychosis. This primacy of the D2 blockade as a mechanism of action has since been disproven. This is the mechanism that leads to gynecomastia, leading to a bevy of lawsuits from men who developed breasts. It also causes related side effects like galactorrhea—breast milk from breasts that can be on men or women who are not nursing— and erectile dysfunction. Dopamine—it does a lot of work in the brain, not just pleasure.This motor side effect profile was not true with clozapine. It had various additional receptors, particularly in the serotonergic family (5HT-2a, for example), and alpha-adrenergic, histaminic, and other receptor sites throughout the brain. This broad profile of different receptors explains the wide range of side effects. But more importantly, these are complex, “messy,” and hard-to-predict outcomes given the complexity of the brain. The complex pharmacology allowed psychiatrists like me to think—hard!—about which particular witches brew of receptors we would choose to tickle (agonize) or antagonize. It's very satisfying. I also suspect this is a story we tell ourselves that is not as closely moored to truth as we'd like. We enjoy thinking about science-ish stuff. Receptor binding profiles are seductive— because they are knowable. Our patient's heart, hope, dreams, and heartbreak? Less so.The most important feature of risperidone today—and its 1st order metabolite, paliperidone—is that is deliverable as pills, rapid-acting dissolvable tablets, and long-acting injectable formulations, lasting between 2 weeks and 6 months between doses. A psychiatric treatment that isn't an oral once-daily pill? One you have to take twice a year? Medicine that is intended for people who often—like many—feel conflicted about taking a daily pill? That is a big enough deal. That is a real innovation— it considers human frailty, ambivalence, and common failures of mind. Not because it's a magic drug. Rather, long-acting medicine that doesn't make crippling relapse easy —thanks to good design— is exactly the kind of medicine that works. My second research effort was on the acceptability of such medicines in youth. It's responsible for my presence at the academic conference where I met my now wife.Oral medicines were popular because they were easy to sell. Novel medicines and technologies will be easy to take. The story of my fascination with the risks and benefits of these medicines doesn't end there, though.I still research these medicines and their adverse effects— funded by NIMH— for identifying Tardive Dyskinesia with Machine Learning and closed-loop Internet of Things physical medication compliance tech with my team at iRxReminder and colleagues at Videra. We are enrolling in a study at Fermata in New York and other sites. Thanks for reading.This article is another in my series about one drug or another. Prior installments include Depakote, Geodon, Ambien, Prozac, Xanax, Klonopin, Lurasidone, Olanzapine, Zulranolone, Benzos, Caffeine, Semeglutide, Lamotrigine, Cocaine, Xylazine, Lithium, dextromethorphan/bupropion and Adderall, etc.Sponsored Content!One way of supporting this publication is buying stuff from Amazon, like a nifty box from Apogee that I used to record the voice-over: the BOOM. In fairness, it's just the A/D. I am also using the API 512c mic pre, plugged into an AnaMod 660 500 series compressor, nestled in a reliable RND R6 Lunchbox, and all of that plugs into the Boom into my Mac. It's a Microtech Geffel mic. Most of the audio post-processing is done with Izotope RX 10. I get money if you purchase any of these things— not a trivial amount since they upped my affiliate rewards.In case anyone was wondering if I was an audio nerd… This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit thefrontierpsychiatrists.substack.com/subscribe

The Frontier Psychiatrists is a newsletter by noted medical content creator Owen Scott Muir, M.D. This series is on individual medicines. Data is presented and referenced, but it's a farewell to prescribing. I learned psychopharmacology, but it's not the focus of my career anymore. Other installments in this series include Klonopin, Lurasidone, Olanzapine, Zulranolone, Benzos, Caffeine, Semeglutide, Lamotrigine, Cocaine, Xylazine, Lithium, dextromethorphan/bupropion and Adderall, etc.I also take requests from subscribers—this whole series is by request from the inimitable Kari Groff. Thanks for reading, and please— support the work!By the 1960s, treatment had been medicalized. The first psychotropic drugs were discovered by serendipity and introduced into psychiatry. The symptom relief they brought was so startling and persuasive that there was a major shift from psychologic to pharmacological treatment.—Leon Eisenberg, M.D., the Stepfather of Laurence B. Guttmacher, M.D.Alprazolam is a benzodiazepine medication that has the brand name Xanax. It has an FDA label for “Panic Disorder, with or without agoraphobia.” In my Klonopin piece, and my prior general benzo review before that, I talked about lipophilicity—how fast a drug can get into the brain, based on how soluble it is in fat. A lipid bilayer protects our brain from drugs inviting themselves in, Willy Nilly.It gets into the brain fast. It has a short half-life—the liver breaks it down rapidly. Xanax is fast in and fast out. Was the drug concocted to be abused? With Xanax, You won't even remember you asked.The world would be better if nobody ever knew it existed. Those doctors who promoted it lied to themselves. One of the Xanax evangelicals told me so himself. Laurence Guttmacher, M.D., is his name. He was an older man when we met. He is very tall. My mother immediately remembered meeting him over a decade ago when I read this article to her on a first pass: “He thanked me for allowing us to train Owen as a psychiatrist,” she noted. He is an advisory dean at the University of Rochester School of Medicine and Dentistry. In the first week of medical school, the first lecture he gave me was about not allowing drug reps into the hospital. Only 15 years later, writing this, do I apprehend how haunted he was by the pharmacology he mid-wifed. He has written a medication guide and an older historical ECT manual, too. He spends time teaching now.Dr. Guttmacher is in the family business. He is a third-generation psychiatrist. His grandfather was the president of the American Eugenics Society—he took over from Margaret Sanger, the champion of the birth control pill. It kept undesirable people from having more children. Laurence Guttmacher is an American Jew. Eugenics was re-purposed from utopian, enlightened, Jewish, and intellectual ideals by Nazis. It was promptly used against the same Jews and other “feebleminded undesirables.” The subsequent rejection of medicalization of psychiatric distress is understandable, among largely Jewish analysts, given Nazis (again, from Drs. Guttmacher and Eisenberg):Psychoanalysis helped psychiatry preserve an abiding interest in the individuality of patients while other medical specialists were losing sight of the patient in their preoccupation with the biology of the disease. It connected the symptoms of mental illness to the psychopathology of everyday life. Psychiatrists learned to help patients by paying attention to their mental symptoms in an era when psychiatry had no procedures. …When [psychoanalysis] was banned from the Congress of Psychology at Munich as ‘a Jewish science' in October 1933, psychoanalysts in Berlin and Vienna began to migrate to the UK and the US. …some 100–200 European analysts and some 30–50 analytically orientated psychologists emigrated to America in the 1930s… the membership of the American Psychoanalytic Association was only 135 in 1936 and almost doubled to 249 by 1944 …[This] influx was as significant intellectually as it was numerically; many refugees … became leaders in the movement.This was Laurence Guttmacher's inheritance—idealism about mind or brain—gone, catastrophically, south. His father and mother were quixotic psychiatrists as well. Psychoanalysis was potent because it explains something. People love explanations— but don't often demand that they be correct. Before the age of oral medicines, psychoanalysis offered these:No other psychologic theory provided what was purported to be so comprehensive an account of the origins of psychopathology. The brain sciences were largely irrelevant to clinical practice. In the mid-century, descriptive psychiatrists were held in little esteem because the diagnosis was unreliable and made little difference in treatment. The psychiatric pharmacopeia was limited to hypnotics and sedatives. This changed with Thorazine. The push towards “biological” explanations continued with the advertising efforts of fellow psychiatrist Dr. Arthur Sackler. His advertising firms, which he purchased and disguised his control of, were behind campaigns for drugs like Valium, Thorazine, Serax, Miltown, and the rest. This was well before his feckless son, Dr. Richard Sackler, took his portion of a family business and murdered undesirables with Oxycodone.Physicians love to be scientific-ish. We love the sense of science. We love an explanation. Laurence Guttmacher loved explanations. Xanax worked—plus, safer than Miltown. As he would later write, doing some heavy editing for his late stepfather:The influence of the authority of one's teachers, the experience of seeing patients improve during psychotherapy (most non-psychotic patients did), the logic and malleability of psychodynamic explanations, and the readiness with which patients desperate for a way out of their dilemmas accepted those explanations combined to make believers of all but the most skeptical of trainees. Those who were non-believers were easily dismissed with ad hominem attacks on their unanalyzed resistance.In that week one lecture in medical school, Dr. Guttmacher was my authoritative teacher. The lesson? Be accountable, even for violations of good sense one has yet to commit.That class featured slides on the percentage of doctors who felt drug representatives had influenced them— according to themselves. A scant one percent admitted to any possibility of influence by industry. The same physicians' opinions about colleagues—99% of them above any influence, remember— were presented on the next slide.In my first week of medical school, Laurence Guttmacher highlighted our credulousness, 40% of the same physicians understood their colleagues would fall under the thrall of attractive drug reps. Physicians were justly suspicious of Pharma's influence on everyone—except ourselves. This, of course, was exactly the pitch Arthur Sackler was making—as far as I can tell, he was an astute psychiatrist.Physicians love to be helpful. What is the most addictive substance for physicians? Samples! We can give them to our patients. We loved it when our office staff were gifted treats. We are “jonesing” to be gracious. We get hooked when people listen to us! Industry paid for all this. Arthur Sackler's disciples were not high on their own supply, unlike individual physicians—intoxicated by how beyond reproach they were. They paid for us to talk to each other, and they paid more if the person being listened to said the right things about Xanax. Administrative staff? Lunch. The same devious machinations of Italian grandmothers—Mangia!— were deployed to influence physicians. There were attractive people to listen to us about how much we cared and our desire to be gracious—the Sacklers ensured it. Arthur was a psychiatrist, after all— someone to hear you out feels good.We had so much to teach. Dr. Laurence Guttmacher researched panic disorder at the National Institute of Mental Health earlier in his career. He was a compelling speaker for Xanax, given his panic disorder pedigree from NIMH.One morning, he awoke to a horrible realization: Xanax wears off after 3-4 hours. Everyone waking up (after 8 hours of sleep) was in Xanax withdrawal. That feels like a panic attack. The obvious cure, next to the bed, was the first of four Xanax tablets as prescribed and recommended—by Dr. Guttmacher in well-appointed dinners—throughout the day. The next day, this cycle of panic would begin again, but this time, worse. And the next day, a little worse still. This was a cycle of self-reinforcing madness. But it moved product.In one of the more demonic decisions ever made, Xanax was formed into a convenient “bar” with four subdivisions. This allowed someone to break 2 mg apart and take 0.5 mg four times a day.No one would ever think to take it all at once. Unless they were anyone, in which case, this is the most immediately obvious strategy.Xanax is a nightmare. It makes opiate—and other— overdoses endlessly more lethal. It's illegal in the UK and should be pulled from the market everywhere. This drug of abuse doesn't need to be an answer to an exam question on medical boards, ever again, unless it is under the “obviously unethical compounds” section.High lipophilicity, short half-life, high potency and poor cross-tolerance, frustrating attempts to switch to less harmful compounds. It is the most toxic in overdose of all the benzodiazepines. Xanax is present in 1 of 20 deaths by overdose.Once the genie is out of the bottle—Xanax will help you forget your woes—it does not stop. Fake bars are fueling death. Xanax is so addictive that counterfeit drug makers use its branding. Why is a prescription drug a better “abuse brand” than street drugs?In total, there were more than 54,000 overdose deaths, including 2,437 with evidence of counterfeit pill use. (CDC, 2019-2021)Xanax is a pox upon the house of medicine, and Laurence Guttmacher, M.D. was eager to blowtorch his very well-reimbursed speaking career when he understood the truth.Laurence Guttmacher, M.D., is an excellent teacher. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit thefrontierpsychiatrists.substack.com/subscribe

Dr. Shannon Westin, Dr. Lakshmi Sandhya, and Dr. Prasanth Ganesan discuss the use of olanzapine to treat chemotherapy-related anorexia, as recently published in JCO. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in-depth on manuscripts published in the Journal of Clinical Oncology. As always, I'm your host, Dr. Shannon Westin, GYN Oncologist and Social Media Editor for JCO. I'm very excited to be here today.  And please note that our participants do not have any conflict of interest.   So we are going to discuss a really exciting paper today entitled the "Randomized, Double-Blind, Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients with Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer." And this was published in the JCO on March 28, 2023, and has gotten a lot of excitement.  And so I'm very thrilled to have two of the authors with me today. First is Dr. Lakshmi Sandhya. She's a Junior Consultant at the SVICCAR Hospital in Tirupati, India. Welcome, Dr. Sandhya. Dr. Lakshmi Sandhya: Thank you so much for the opportunity to be here. Dr. Shannon Westin: And I also have the senior author here today, Dr. Prasanth Ganesan. He is a Professor in the Department of Medical Oncology at JIPMER, which is the Jawaharlal Institute of Postgraduate Medical Education and Research in Puducherry, India. Welcome, sir.  Dr. Prasanth Ganesan: Thank you. Thank you very much, Dr. Westin. It's good to be here. Thank you very much.  Dr. Shannon Westin: Great to have you both. So we're going to get right to it. I think this is an excellent paper and certainly something we see across many of our patients who are diagnosed with cancer and who are receiving treatment for cancer. But first, I want to level set. What is the true definition of chemotherapy-related anorexia, and really approximately how many patients do you think it impacts?  Dr. Prasanth Ganesan: As you know, anorexia itself is very common in advanced cancers. Almost like maybe 80%, 90% of patients have some form of anorexia. But at diagnosis, it depends on the type of cancers. Very high in upper GI cancers, esophagus, stomach, pancreas, or lung cancer. But when we talk about chemotherapy-related anorexia, we specifically mean anorexia that is brought on or probably worsened by chemotherapy. So this depends a lot on the regimen that is used. So studies in lung cancer, upper GI cancer that have used something like platinum agents, maybe as high as 50% to 80%. Now, the challenge is how much of it is contributed by the underlying cancer itself and how much of it is worsened by the chemotherapy. It's tough to say, but I think we all have seen that chemotherapy does kind of really increase the anorexia in many of these patients. So I would say the problem is common. Depends on the type of cancer, the type of agent being used, and also sometimes on how intently we are looking for it. Dr. Shannon Westin: You bring up a great point in really kind of making sure that we're screening our patients for it and understanding who's actually experiencing those things. And I do think putting it on our list of things that we, on a day-to-day basis, discuss with our patients is really relevant, although I will say sometimes we haven't done that because we don't have a good treatment. So that's what makes your paper so exciting. But before we get into the results of the paper, why don't we talk a little bit more about some of the factors that contribute to anorexia? Dr. Sandhya, I don't know if you want to elaborate a little bit on some of those. Dr. Lakshmi Sandhya: Yeah. So most important would be the cancer type and the type of chemotherapy agent being used. So, as we mentioned, some cancer types have high anorexia incidence even at baseline. So the most important and prominent would be the upper gastric cancers and the pancreatic and lung cancer. Among the chemotherapy types, I think the platinum agents are known to cause anorexia more often and also associated with nausea or vomiting. So anorexia and weight loss is not very common in other cancers like breast, if you see, or ovarian cancer during the therapy. In fact, there has been weight gain in most of the patients with breast cancer, and most of the data which comes from breast cancer show that weight loss is experienced only by around 5% of the patients. So we would say the factors contributing most commonly would be the type of cancer and the chemotherapy that is being used.  Dr. Shannon Westin: Yeah, I think it's a great point. As a gynecologic oncologist, we do a lot of platinum, but we balance it, especially in upfront with paclitaxel or taxanes and we're giving steroids as premeds for them. And so we definitely see patients expecting to lose weight and instead actually getting hungry with the steroid use and eating to some degree.  Dr. Prasanth Ganesan: So I just want to add that even targeted agents, when you use something like sunitinib or everolimus, some of these agents, even they have got anorexia, probably 20% to 30%. So we did not include them in our study, but I'm just saying that even with targeted agents, we do get anorexia, at least some of them. So it's a problem across them. Dr. Shannon Westin: Yeah, we've been using PARP inhibitors and definitely can see that nausea, vomiting, and anorexia in that population. So I appreciate you making a point that that wasn't included but could be potentially extrapolated here. And then I guess the other question that I have is how does anorexia impact cancer-related outcomes? Does it have an impact in that way? Dr. Prasanth Ganesan: I believe it does, but it's probably not in a direct sort of way. So anorexia is strongly associated with weight loss and some amount of cachexia, and weight loss per se has been associated with poor outcomes across the board. There's a lot of data, especially in lung, upper GI cancers, and even head and neck cancer where weight loss before or during therapy has been associated with poor survival impact. So, again—in pancreatic cancer, it's associated with poor survival. So it's difficult to pin the weight loss only on anorexia here because weight loss is often multifactorial, but yeah, anorexia is probably a significant factor which is also adding to that. So I would say indirectly, yes, anorexia has an impact on cancer-related outcomes. Yes.  Dr. Shannon Westin: And I guess just getting into kind of what we can do before we get into the novel findings in your study, I know we've tried to talk about some dietary-related interventions that we can utilize to combat anorexia. Anything that you all have found to be most helpful from a diet standpoint?  Dr. Lakshmi Sandhya: So, from the diet standpoint, I would say dietary counseling is generally recommended for all the patients. To be very frank, we don't usually have a dietitian to spare at our outpatient clinic to counsel all the patients. So this is not something we are able to practice in the clinic. But in this trial, of course, we had a dietitian who counseled all the patients, and she gave them a diet chart to follow and gentle advice on what item to use and which is good, specifically emphasizing on high-calorie and high-protein diet. So we did not find that any particular dietary intervention is impactful. If you've seen various studies on dietary intervention, they have shown mixed results on improvement of anorexia or weight gain. So we're not sure whether dietary counseling particularly has impacted the results. Dr. Prasanth Ganesan: Yes. Dr. Shannon Westin: Okay. And then I imagine that would be one of the reasons that led to your exploration of this agent of olanzapine to treat chemotherapy-related anorexia. And can you just walk us through any data that existed kind of prior to your study to support this work? Dr. Prasanth Ganesan: Yeah, definitely. I think olanzapine has been in the news for the last decade or so because we've been using it consistently for vomiting and nausea in patients getting emetogenic therapies. So there are at least three studies which we found for olanzapine in cancer anorexia. I think one was from Dr. Navari, and he had done a randomized trial comparing megestrol with megestrol plus olanzapine. And this was done in patients with advanced cancers, and they found about 35% of the patients in the olanzapine group had additional weight gain. So it was useful. And this was not a very recent study. It's almost done about 10 years back. Dr. Shannon Westin: Oh, wow. Dr. Prasanth Ganesan: Then, after that, there was an interesting phase I study by Dr. Naing, and that was from MD Anderson, and that looked at various doses of olanzapine also. And that was interesting for us because that's where we got our starting dose of 2.5 mg because even at this dose, there was an effect on anorexia. So that was a very useful study because we were also trying to figure out what is the best dose to use in our trial. So that's why we went with the 2.5 mg.  Dr. Shannon Westin: That's great. I know everyone's excited to hear about the results. So, Dr. Sandhya, do you want to walk us through the design of the study and maybe how you chose your patient population? I think you've already kind of hinted at it, taking people that at baseline have high levels of anorexia.  Dr. Lakshmi Sandhya: Yes, sure. So this was designed as a phase III randomized blinded trial. So we used olanzapine in one arm and the matched placebo in another. So we gave olanzapine at a dose of 2.5 mg once a day for 12 weeks. And similarly, a placebo which looked similar was given to the other group. So we assessed for weight gain as an objective measure and improvement in appetite as one of the endpoints, which is more of a subjective measure. And we wanted to focus on population where the problem of anorexia was maximum. So we focused on upper GI, lung and pancreas, and biliary tract cancers to make it more uniform when it comes to anorexia. Dr. Prasanth Ganesan: Just to add a point that, even though we had included three or four types of cancer, almost 60% of our patients were actually gastric cancer patients because that probably reflects the profile of patients that we see at our center. It's a very common cancer in our place, and the next common was the lung cancer. We had only about 15% of patients who had pancreaticobiliary cancer. Dr. Shannon Westin: That makes sense. Obviously, wherever we're enrolling is what we're going to see, but I think hopefully these data can be extrapolated across all cancer types. So you mentioned that your primary endpoint was weight loss as well as the improved appetite. Can you walk us through, Dr. Sandhya, what you found? What were your results? Dr. Lakshmi Sandhya: So we had two primary endpoints. One was weight gain, and the other was improvement in appetite. So we wanted to use weight gain, as I said, since we felt that it is more of an objective measure than measuring anorexia. And olanzapine in our trial improved weight more than 5% from baseline in 60% of the patients in the olanzapine group and 9% in the placebo. Correspondingly, we have also measured improvement in appetite by using various questionnaires, which are validated. So one was visual analog scale, and the other was FAACT AC subscale, which we used during this trial. So yes, olanzapine worked well. We had hoped to show improvement in weight in about 30%, but surprisingly, we found that the weight gain was about 60% in the olanzapine group.  Dr. Shannon Westin: That's so great. It's always nice when you outperform your wildest dreams. So congratulations. Were there other secondary endpoints you observed that were impacted by the olanzapine?  Dr. Prasanth Ganesan: Yeah. So we did have a bunch of secondary endpoints because, again, we were worried when we started off because this is a subjective endpoint and we're not really sure how it's going to pan out. So we looked at some endpoints like quality of life, obviously, and we also had some nutritional assessment with the SDA and consistently, all of these showed improvement with the olanzapine. And what is most interesting for us was the grade III/IV side effects of the chemotherapy regimens, and these were reduced in the olanzapine. So this was something which we were looking for because consistently—we had also done some earlier studies in elderly populations where we found that the nutrition was an important factor in determining the toxicities of therapy. So that's why we wanted that as an endpoint.  And in fact, we found that patients who started at lower doses in cycle one due to poor performance status and nutrition, many of them could actually increase their dose in their subsequent cycles and this was more commonly seen in the olanzapine arm. So this was something which was very pleasant and which was something which we found was very interesting. So we could deliver more better chemotherapy intensity in these patients, thanks to their better nutrition.  Dr. Shannon Westin: That's so exciting. Such a nice concrete thing for patients as well. I mean, obviously being able to gain weight is something that they could see and having that appetite, but knowing that they had less side effects from their chemo as well is such an important impact. I guess, on the converse side, were there any negative impacts to the olanzapine?  Dr. Lakshmi Sandhya: Not really. We specifically asked patients about olanzapine-induced side-effects like drowsiness. At this dose of 2.5 mg per day, we found very little side-effects which would be attributed to olanzapine. As we mentioned, overall side-effects were also lowered in olanzapine arm. So with short duration of three months and at this dose, we believe that olanzapine is fairly safe. Dr. Shannon Westin: And that's great. And I'd be remiss—especially here in the States, this is high discussion around financial toxicity. As I recall, it's a pretty inexpensive agent. Is there any kind of negative financial impact for the use of this drug?  Dr. Prasanth Ganesan: Yeah, this is the best part. In India, for three months, olanzapine costs about 300 rupees. That would be like $4 or something for three months of therapy. I think that's pretty easily affordable across the board. Most patients here can easily buy this. And I'm not sure about the cost in the US, but I'm guessing it would not be too high. It's been around for some time. It should be out of patent and things like that. So I think it's a very inexpensive drug.  Dr. Shannon Westin: Yeah, we like that, like reuse of an old drug to do something good. The other question I had for you all is just any thoughts about how these results might compare to other things that we use, like glucocorticoids or progestational agents? I know we didn't have that as a comparator, but just your thoughts on that. Dr. Prasanth Ganesan: So, in terms of efficacy in reducing anorexia, it's difficult to compare because, if you see the studies of steroids and megestrol, most of them have been done by patients with more advanced cancers, not necessarily patients who are getting chemotherapy in the front line. But we think the side-effect profile is what gives an advantage to olanzapine because three months of steroids, even if you say lower doses of dex at 4mg or something, which I would want to use in a newly diagnosed cancer patient. Megestrol also seems to have problems like DVT and is actually much more expensive, at least in our context. I mean, if you compare with these aspects, I would definitely put olanzapine ahead, but as you said, this is not a direct comparison between those so-called existing agents. Dr. Shannon Westin: Yeah, I think that's a very thoughtful answer, but I think something we just needed to cover, even though we know that it wasn't a randomized trial between those two. Any limitations, Dr. Sandhya, on these results? Anything that you wish you had done a little differently? Dr. Lakshmi Sandhya: Yeah. As such, it is applicable only in the context of upper GI and lung cancers, as we have mostly included upper GI and lung cancers, and most of the patients, almost two-thirds of the patients included in our study, were gastric cancers. So also the duration that we used was only for 12 weeks. So we don't know whether longer duration will benefit more or harm. And the sustainability of weight beyond 12 weeks, we have not actually looked into. So, yeah, maybe these are few limitations that we can think about. Dr. Shannon Westin: That's very true. And I think that—I mean, obviously, when we design trials, we have to have a limit. Do you have plans—are you able to follow these patients out a little further? Do you know if clinically they're continuing it off-trial?  Dr. Prasanth Ganesan: So we have done that. So we have been following them for their survival data, and we just completed the analysis. So I think we have to really publish that next. So it is looking interesting. So some interesting data there. So that's something which we found it very exciting. Dr. Shannon Westin: Okay, good. Dr. Prasanth Ganesan: So that is something which is out there. And we also looked at some data on improvement of their muscle mass and on their CAT scans, we looked at that. So that's also something which we are trying to analyze and see whether we can have more concrete or objective endpoints in terms of improvement of the muscle mass and adipose tissue and things like that. Dr. Shannon Westin: Okay, good. Well, we'll look forward to that in a future version of the JCO, I hope. I guess the last thing is where do we go from here? You kind of hinted at this a little bit. I'm kind of bummed because I was ready to start implementing this in my clinic tomorrow. Dr. Prasanth Ganesan: So it's just safe, it's effective, and it's cheap. So I don't see any reason we should not start implementing something like this straightaway. I use it quite commonly, definitely for patients who are part of the trial population. And even for any patients with advanced cancer on or off chemotherapy with anorexia or weight loss, I'm comfortable to use olanzapine at least for a short term. And many patients at least they come back and say that it does help them. And I've not seen any side-effects at this dose of olanzapine. So it seems very safe to use. I'm comfortable to put it in the clinic right away.  Dr. Shannon Westin: Dr. Sandhya, what do you think?  Dr. Lakshmi Sandhya: I feel, in this trial, we came across the safety part of it and also the affordability part of it, and definitely it has been very encouraging results, so yeah. So, day-to-day practice, it can be used. Dr. Shannon Westin:  Well, great. I think this is super-educational, and I hope everyone else is just as convinced as I am how important this work was and how potentially impactful it will be for our patients. I just want to again thank these wonderful physicians and researchers. Dr. Sandhya, Dr. Ganesan, thank you so much for your time and a little bit of a late time for this taping across the globe. So thanks again for being here. Dr. Prasanth Ganesan: Thanks, Dr. Westin, for giving us this chance.  Dr. Lakshmi Sandhya: Thank you so much. Dr. Shannon Westin: So, again, y'all, this has been JCO After Hours discussing the important paper, "Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer,” published March 28th, ‘23. We are just so grateful that you joined us and hope you'll check out the other podcast offerings on the website. Take care. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

This is the 18th podcast episode for the Psychiatric Medication Podcast Series. Series Description: Current literature indicates that podcasts can be an effective educational format to reach health professionals across the continuum of medical education, addressing a myriad of topics pertinent to providers. This episode serves as an overview of Olanzapine/Zyprexa. This podcast season is the second released by East Carolina University's Office of Continuing Medical Education and may be beneficial for physicians, residents, fellows, nurse practitioners, physician assistants, and nurses. This podcast season is comprised of approximately 30 episodes, each focusing on different psychiatric medications for the non-psychiatric provider. Those tuning into the podcast's second season will receive a primer on the "bread and butter" behavioral health medications for primary care: antidepressants, antipsychotics, and mood stabilizers. Episodes will be released weekly on Wednesdays.Rachel Gooding, MD & Maxwell Miller, DO

In this episode, we examine the tolerability, safety, and effectiveness of low-dose olanzapine in adolescents with anorexia nervosa (AN). Learn about the potential benefits and risks of using olanzapine in AN patients and the importance of a multidisciplinary approach in treating this challenging population. Faculty: David Rosenberg, M.D. Host: Richard Seeber, M.D. Learn more about our membership here Earn 0.5 CMEs: CAP Smart Takes Vol. 05 Low-Dose Olanzapine for Treating Adolescents With Anorexia Nervosa

Lots of updates: Olanzapine increases weight gain, QOL in some advanced cancer: https://pubmed.ncbi.nlm.nih.gov/?term=36977285 Chemotherapy Toxicity - When Less is More: https://www.nejm.org/doi/full/10.1056/NEJMcibr1202395 Pembro + Chemo improves PFS > chemo alone in advanced endometrial cancer: https://www.nejm.org/doi/full/10.1056/NEJMoa2302312 Enfortumab vedotin + pembrolizumab gets an accelerated approval for cisplatin-ineligible patients with urothelial carcinoma. Safety signals seen.

Download the cheat: https://bit.ly/50-meds  View the lesson:   Generic Name olanzapine Trade Name Zyprexa Indication schizophrenia, mania, depression, anorexia nervosa, nausea/vomiting related to chemotherapy Action antagonizes dopamine and serotonin Therapeutic Class antipsychotic, mood stabilizers Pharmacologic Class thienobenzodiazepines Nursing Considerations • do not use while breastfeeding • can cause neurolyptic malignant syndrome, seizures, suicidal thoughts, insomnia, tardive dyskinesia, agranulocytosis, constipation, tremors • assess mental status • monitor hemodynamics • assess blood sugars • assess intake and output • monitor liver function tests

https://psychiatry.dev/wp-content/uploads/speaker/post-10592.mp3?cb=1666996313.mp3 Playback speed: 0.8x 1x 1.3x 1.6x 2x Download: Reduction in Multiple Cardiometabolic Risk Factors With Combined Olanzapine/Samidorphan Compared With Olanzapine: Post Hoc Analyses From a 24-Week Phase 3 StudyFull EntryReduction in Multiple Cardiometabolic Risk Factors With Combined Olanzapine/Samidorphan Compared With Olanzapine: Post Hoc Analyses From a 24-Week Phase 3 Study –

With five sessions down, Natasha feels less like a nurse and more like a patient. Her final chemo treatment is next Wednesday, and the planned end-of-chemo celebration feels fake because surgery and radiation are still ahead. Because food tastes even worse than before, she lives off rice and beans. To keep the weight loss from further eroding her self esteem, she downloads an app to send her daily affirmations. Links Support the Breast Cancer Stories podcast https://www.breastcancerstoriespodcast.com/donate Subscribe to our newsletter here: http://eepurl.com/hX12YD About Breast Cancer Stories Breast Cancer Stories follows Natasha Curry, a palliative care nurse practitioner at San Francisco General Hospital, through her experience of going from being a nurse to a patient after being diagnosed with breast cancer. Natasha was in Malawi on a Doctors Without Borders mission in 2021 when her husband of 25 years announced in a text message that he was leaving. She returned home, fell into bed for a few weeks, and eventually pulled herself together and went back to work. A few months later when she discovered an almond-sized lump in her armpit, she did everything she tells her patients not to do and dismissed it, or wrote it off as a “fat lump." Months went by before Natasha finally got a mammogram, but radiology saw nothing in either breast. It was the armpit lump that caught their attention. Next step was an ultrasound, where the lump was clearly visible. One painful biopsy later, Natasha found out she had cancer; in one life-changing moment, the nurse became the patient. This podcast is about what happens when you have breast cancer, told in real time. Host and Executive Producer: Eva Sheie Co-Host: Kristen Vengler Editor and Audio Engineer: Daniel Croeser Theme Music: Them Highs and Lows, Bird of Figment (https://music.apple.com/us/artist/bird-of-figment/1434663902) Production Assistant: Mary Ellen Clarkson Cover Art Designer: Shawn Hiatt Breast Cancer Stories is a production of The Axis. (http://www.theaxis.io/) PROUDLY MADE IN AUSTIN, TEXAS

Is it possible to safely come off psychiatric medications associated with the consequences of a brain tumor? 29 y.o. Tina and her mom, Janine, share their experiences as Tina heals from a cerebellar tumor at 17 y.o. and then a mental health crisis ten years later. Diagnosed with bipolar disorder and medicated with Lamictal and Olanzapine, Tina felt flat, tired, and stressed. How did she overcome her life challenges? What important insights does she have for those who also want to taper off their psychiatric medications? This podcast will inspire hope as Tina and Janine share their miraculous healing journey.For more about Dr. Lee, please visit:Website: www.holisticpsychiatrist.comYouTube: The Holistic PsychiatristClick on the Holistic Updates Sign up for weekly stories and insights: Holistic UpdatesTo schedule consultations or appointments, call her office at 240-437-7600The content provided by this podcast is for informational purposes only and has not been approved by the U.S. FDA. This podcast is not intended to provide personal medical advice, which should be obtained from a medical professional.

Lybalvi combines olanzapine with the opioid blocker samidorphan in hopes of curbing the weight gain on that antipsychotic. Here, we look at how well it works.CME: Take the CME Post-Test for this episodePublished On: 02/28/2022Duration: 25 minutes, 03 secondsEarn CME credits for this episode through the link in the podcast notes, and if you haven't subscribed to the online issue give us a try, and take $30 off your first year's subscription with the promo code PODCAST. Your support helps us operate free of industry influence.Chris Aiken, MD, and Kellie Newsome, PMHNP, have disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.

Olanzapine is one of the hardest antipsychotic medications to taper off safely. Its psychoactive effects impact dopamine, histamine, muscarinic, adrenergic, and serotonin receptors. To lower it without relapsing once again into psychosis requires healing underlying causes and one's dependency on Olanzapine over time. Camille shares her successful healing journey, and what she learned along the way that will inspire and support others. For more about Dr. Lee, please visit: Website: www.holisticpsychiatrist.comYouTube: The Holistic PsychiatristClick on the Holistic Updates Sign up for weekly stories and insights: Holistic UpdatesTo schedule consultations or appointments, call her office at 240-437-7600 The content provided by this podcast is for informational purposes only and has not been approved by the U.S. FDA. This podcast is not intended to provide personal medical advice, which should be obtained from a medical professional.

Episode 76: Eating Disorders. The malaria vaccine is announced by Dr Parker, eating disorders such as anorexia and bulimia are briefly discussed by Sophia, Jeffrey and Dr Arreaza. Introduction: Introducing the malaria vaccine (RTS,S)Written by Hector Arreaza, MD; read by Tana Parker, MD.  Today is November 26, 2021.Malaria is a devastating disease that continues to kill thousands of people every year around the world. Since the year 2000, there have been 1.5 billion cases of malaria and 7.6 million deaths. In 2019, there were 229 million new cases, and 409,000 deaths, mostly children under 5 years of age.Effective vaccines for many protozoal diseases are available for animals (for example, the vaccine against toxoplasmosis in sheep, babesiosis in cows, and more.) However, vaccines for protozoal disease in humans had not been widely available … until now. The RTS,S is a vaccine against malaria approved by the European Medicines Agency in July 2015 for babies at risk, and it was rolled out in pilot projects in Malawi, Ghana and Kenya in 2019.  In October 2021, the World Health Organization announced the recommendation of this anti-malaria vaccine. The trade name of this vaccine is Mosquirix®. The vaccination is recommended for children in sub-Saharan Africa and other regions with moderate to high transmission of Plasmodium falciparum, which is considered the deadliest parasite in humans.  The approved vaccine has shown low to moderate efficacy, preventing about 30% of severe malaria after 4 doses in children younger than five years old. Implementation of vaccination is not free from challenges, and it should be executed not as the solution for the disease, but as part of the solution, along with other efforts such as mosquito control, effective health care, and more.RTS,S is an add-on to continue the fight against malaria worldwide. Hopefully we can lighten the heavy burden of malaria for more than 87 countries that suffer the severe consequences of poor control of this devastating disease. This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. ___________________________Eating Disorders. Written by Sophia Dhillon, MS3, Jeffrey Nguyen, MS3. Discussion with Hector Arreaza, MD.  This is not intended to be a comprehensive lecture on eating disorders. This episode is intended to give you basic information, hoping to motivate you keep learning about it. Let's start talking about eating disorders today, specifically anorexia nervosa and bulimia nervosa. What is an eating disorder? An eating disorder is a disturbance of eating that interferes with health. As a reminder, health is “a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity.” So, an eating disorder, in a wide context, is any eating pattern that is out of what is considered “normal”, and that variation in feeding causes health problems. But in general, when we talk about eating disorders in medicine, we refer to anorexia nervosa and bulimia nervosa, but it includes also avoidant/restrictive food intake disorder, binge eating disorder, night eating disorder, pica, and rumination disorder.  ANOREXIAIn general, anorexia is characterized by immoderate food restriction, inappropriate eating habits or rituals, obsession with having a thin figure or an irrational fear of weight gain as well as distorted body self-perception. There are 2 main subtypes of anorexia: restricting type vs binge-eating/purging type. Tell us the difference between anorexia restrictive type and binge eating-purging type.Anorexia, restrictive type is when weight loss is achieved by diet, fasting and/or excessive exercise, meanwhile the binge-eating/purging type entails eating binges followed by self-induced vomiting and/or using laxatives, enemas or diuretics. These patients will have intense fear of gaining weight or becoming fat. They will have a distorted perception of body weight and shape or denial of the medical seriousness of one's low body weight.Anorexia nervosa is different than avoidant/restrictive food intake disorder. In anorexia, you have an altered perception of your body (“I'm fat”), but in avoidant/restrictive food intake disorder, your perception of your body weight and shape is not abnormal. “I'm skinny, and I'm OK with that.” This is new information for me. I thought anorexia was present always when a patient refused to eat, whether you liked your body or not.Why do people develop eating disorders? There are so many reasons why people develop eating disorders. First, it can be psychological due to low self-esteem, feelings of inadequacy or failure, feeling of being out of control, response to change (i. e. puberty) or response to stress. Second, it can be due to interpersonal issues like having trouble with family and personal relationships, difficult expressing emotions or feelings, or even history of being teased based on size or weight. Lastly, it is the social and cultural norms that we grow up in. There are cultural pressures that glorify thinness and place value on obtaining the perfect body, narrow definitions of beauty that include women and men of specific body weights and shapes. Sometimes there is no reason. Some people just get obsessed with their weight and perceive themselves as “fat”. Effect of anorexia on different parts of the bodySince these patients are scared of gaining weight, how does it affect the entire body?Anorexia can affect multiple systems in our body. Just to name a few symptoms that it can manifest as: amenorrhea, infertility, constipation, dizziness, hypothermia, bradycardia, hypotension, dry skin and even hair loss. Starvation induces protein and fat catabolism that leads to loss of cellular volume and atrophy of the heart, brain, liver, intestines, kidneys, and muscles. Cardiac: It can decrease cardiac mass, decrease cardiac chamber volumes, cause myocardial fibrosis and pericardial effusion. These manifestations are reversible if the patient gains weight. Functionally, it can cause bradycardia due to increased parasympathetic activity, hypotension, decreased heart rate variability and QT prolongation on ECG. Lungs: shortness of breath due to weakened and wasting of the respiratory muscles, pneumothorax and aspiration pneumonia. GI system: it leads to gastroparesis with bloating, constipation, severe pancreatitis and mild transaminitis. Hematologic: anemia, leukopenia and thrombocytopenia. Skin manifestations include dry/scaly skin, hair loss, acne, hyperpigmentation and acrocyanosis. You can also find lanugo, which is a very thin, light colored hair on the face and body. It is thought that the lanugo is an adaptation from the body to keep it warm. Lanugo is common in patients with anorexia nervosa or other causes of malnourishment. That's why wearing coats in warm weather can be a silent sign of anorexia. Other subtle signs include social withdrawal, fidgeting (to burn calories), and always “eating” in private.  It is important to remember that all these manifestation that Jeffrey mentioned are not present with intermittent fasting because intermittent fasting is an intermittent restriction of food, the nutritional needs are met during the “feasting” periods after “fasting”. Some may argue that intermittent fasting may promote eating disorders, but I believe intermittent fasting is just an effective treatment for obesity.Treatment plan for anorexiaThere are several treatment options for these patients. We can refer them to nutritional rehabilitation where they can supervise meals. We can refer them to psychotherapy, such as cognitive behavioral therapy or motivational interviewing. There is also a drug called Olanzapine for this condition. Sometimes, patients may need admission to the hospital. I learned recently that UCLA has an Eating Disorder Program which includes inpatient services. Some centers are very specialized and include family therapy and group therapy. Listeners, you can continue to research about anorexia, it's is fascinating. The prevalence of anorexia in the US is estimated to be 0.6%[3]. BULIMIABy definition, bulimia nervosa is when a person binge eats and then uses certain behaviors to prevent weight gain. These behaviors may include self-induced vomiting, using laxatives or diuretics, exercising excessively, or fasting and having a restrictive diet. Signs and symptoms to look forA physical examination is key. On physical presentation, these people usually can have overweight or obesity. That's the main difference with anorexia. Anorexia: skinny people, bulimia: normal weight, overweight or obesity. Regardless of their weight, these patients are malnourished. They may lack some essential nutrients causing serious health consequences. That's why nutrition cannot be assessed by BMI only. Common signs they will present with will include tachycardia, hypotension (systolic blood pressure below 90), dry skin, and hair loss. If the person uses self-induced vomiting to prevent weight gain, they may have erosion of the dental enamel from all the acid that comes up when they vomit. There may also be scarring or calluses on the dorsum side of the hand from all the acid too. Their parotid glands, that are located on the side of the jaws will also be swollen, causing a sign known as chipmunk face of bulimia.From talking to this person and getting a detailed history, we will learn of the symptoms bulimia nervosa can cause. This will include lethargy and fatigue, irregular menstrual periods in a female, abdominal pain and bloating, and constipationThis disorder really does take a toll on the body. There's plenty of complications that come with it as well. Let's try to break it down by system. GI system has the most complications: esophageal tears from the vomiting called Mallory-Weiss syndrome, which will present with bloody vomits, a loss of gag reflex, esophageal dysmotility, abdominal pain and bloating, GERD, diarrhea and malabsorption of nutrients, fatty stools known as steatorrhea, colonic dysmotility leading to constipation, irritable bowel syndrome, rectal prolapse, and pancreatitis. Cardiac: serious complication is ipeac-induced myopathy, let's spend a little time on this. Ipecac is a syrup that someone with bulimia nervosa may use to make themselves vomit. If a person uses this syrup frequently or for a long amount of time, there is a component called emetine will accumulate in muscle, including cardiac muscle. If a person uses ipecac chronically, it can be detected in the urine for up to 60 days. This will damage the heart muscles or myocardium and lead to cardiomyopathy. It will present with symptoms such as chest pain, shortness of breath, hypotension, tachycardia or bradycardia, T wave abnormalities on ECG, conduction delays, arrythmias, pericardial effusions, and even congestive heart failure. Cardiomyopathy may be irreversible. Renal system: dehydration, hypokalemia, hypochloremia, hyponatremia, and metabolic alkalosis. This could happen in patient who use diuretics as a purging mechanism. Endocrine system: Electrolytes and hormones imbalance. The endocrine system primarily impacts the reproductive and skeletal systems. Among 82 women treated for bulimia nervosa, menstrual irregularities were present in 45 percent at pretreatment and in 31 percent at 12-month follow-up. These irregularities may look like spotty or very light menstrual cycles. Cycles may be very erratic or completely absent. Skeletal system: osteopenia and osteoporosis are common with bulimia nervosa. Osteopenia means weaker and more brittle bones. Osteoporosis is more serious than osteopenia and can more easily result in fractures.The diagnosis of bulimia nervosa can usually be made clinically. And after the diagnosis with bulimia nervosa, the first step in helping them is always getting a full lab work up to see what systems to the body have been impacted. Treatment options include nutritional counseling, behavioral therapy, and even medications. If a person needs help connecting with someone that can help with this disorder, there are organizations that they can contact which will connect them with proper resources in their area. Organizations include the Academy for Eating Disorders and the National Eating Disorders Association. Bulimia nervosa is more prevalent in females than males in all age groups. In the US, adult prevalence is 1.0% and adolescent prevalence is 0.9%, with the median age of onset of 18 years. After comparing different age groups, we have seen the prevalence of bulimia nervosa has increased over time. Conclusion: Anorexia nervosa and bulimia nervosa are eating disorders that can have consequences on the health of our patients. We should know the difference between these two diseases and know the resources available in our community to assist these patients. The diagnosis may be done clinically, but you will need to order labs or imaging for a full assessment. Eating disorders are an example of the direct effect a mental illness can have in the body. In the specific case, anorexia and bulimia cause malnutrition. The treatment of these diseases requires a multidisciplinary team to treat the patient and the family as well.____________________________Conclusion: Now we conclude our episode number 76 “Eating Disorders.” We started this episode with exciting news about the new malaria vaccine, a step forward on our fight against malaria. Sophia, Jeffrey, and Dr Arreaza presented an interesting overview about anorexia and bulimia. They taught us that if a patient perceives him or herself as “fat”, but they are actually underweight, they may have anorexia. Patients with bulimia tend to have normal or above normal BMI but have periods of binging and purging. Be aware of these conditions while assessing your patients' nutritional status and treat appropriately or refer as needed. Even without trying, every night you go to bed being a little wiser.Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email RBresidency@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Tana Parker, Sophia Dhillon, and Jeffrey Nguyen. Audio edition: Suraj Amrutia. See you next week! _____________________References: Malaria's Impact Worldwide, Centers for Disease Control and Prevention, https://www.cdc.gov/malaria/malaria_worldwide/impact.html, accessed on November 15, 2021.  Constitution of the World Health Organization, Basic Documents, Forty-fifth edition, Supplement, October 2006, accessed on Aug 26, 2021. Accessed on November 15, 2021.  https://www.who.int/governance/eb/who_constitution_en.pdf. 12 Secret Signs of Anorexia, CBS News, August 12, 2010, https://www.cbsnews.com/pictures/12-secret-signs-of-anorexia/3/.  Hudson JI, Hiripi E, Pope HG Jr, Kessler RC. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry. 2007 Feb 1;61(3):348-58. doi: 10.1016/j.biopsych.2006.03.040. Epub 2006 Jul 3. Erratum in: Biol Psychiatry. 2012 Jul 15;72(2):164. PMID: 16815322; PMCID: PMC1892232. https://pubmed.ncbi.nlm.nih.gov/16815322/.  Mitchell, James E, MD; and Christie Zunker, PhD, CPH, CHES, Bulimia nervosa and binge eating disorder in adults: Medical complications and their management, UpToDate, October 2021. https://www.uptodate.com/contents/bulimia-nervosa-and-binge-eating-disorder-in-adults-medical-complications-and-their-management?search=Bulimia%20nervosa%20and%20binge%20eating%20disorder%20in%20adults:%20Medical%20complications%20and%20their%20management&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 Yager, Joel, MD, Eating disorders: Overview of epidemiology, clinical features, and diagnosis, UpToDate, October 2021. https://www.uptodate.com/contents/eating-disorders-overview-of-epidemiology-clinical-features-and-diagnosis?search=Eating%20disorders:%20Overview%20of%20epidemiology,%20clinical%20features,%20and%20diagnosis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 Yager, Joel, MD, Eating disorders: Overview of prevention and treatment, UpToDate, October 2021. https://www.uptodate.com/contents/eating-disorders-overview-of-prevention-and-treatment?search=Eating%20disorders:%20Overview%20of%20prevention%20and%20treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

It's the JournalFeed Podcast for the week of September 20-24, 2021. We cover EM workforce projections, ETCO2 for OHCA in PEA, NSAIDs and non-union risk, IM droperidol vs olanzapine for agitation, and IM ketamine vs midazolam/haloperidol for agitation.

Contributor: Nick Tsipis, MD Educational Pearls: Prospective trial studied 5 mg IM droperidol to 10 mg IM olanzapine (Zyprexa) in the reducing levels of agitation Time to adequate sedation was about 16 minutes for both agents Droperidol was slightly less sedating than olanzapine and length of stay for olanzapine was longer Olanzapine had a higher rate of requiring another agent for adequate sedation Droperidol had a higher rate of adverse events (mainly extrapyramidal symptoms) than olanzapine Remember to put the safety of the staff and patient at the forefront of sedation practices and be cognizant of the psychological effect of giving involuntary medications to patients References Cole JB, Stang JL, DeVries PA, Martel ML, Miner JR, Driver BE. A Prospective Study of Intramuscular Droperidol or Olanzapine for Acute Agitation in the Emergency Department: A Natural Experiment Owing to Drug Shortages. Ann Emerg Med. 2021;78(2):274-286. doi:10.1016/j.annemergmed.2021.01.005 Summarized by John Spartz, MS4 | Edited by Erik Verzemnieks, MD   The Emergency Medical Minute is excited to announce that we are now offering AMA PRA Category 1 credits™ via online course modules. To access these and for more information, visit our website at https://emergencymedicalminute.org/cme-courses/ and create an account.  Donate to EMM today!

Drs Kurt DeVine & Heather Bell continue the series on drugs felt to be safe…. But are not necessarily! In Episode #8 of “Safe Drugs- or Not” we discuss olanzapine aka Zyprexa, another second-generation antipsychotic! FDA approved for schizophrenia and bipolar but often used off label for anxiety, insomnia and many more things- especially in correctional settings! To learn more about the doctors as well as keep up with current happenings follow us on twitter: @echocsct and Facebook: @theaddictionconnectionhk

Drs Kurt DeVine & Heather Bell continue the series on drugs felt to be safe…. But are not necessarily! In Episode #8 of “Safe Drugs- or Not” we discuss olanzapine aka Zyprexa, another second-generation antipsychotic! FDA approved for schizophrenia and bipolar but often used off label for anxiety, insomnia and many more things- especially in correctional settings! To learn more about the doctors as well as keep up with current happenings follow us on twitter: @echocsct and Facebook: @theaddictionconnectionhk

The Whole View, Episode 448: Marijuana and Gut Health Welcome back to episode 448! (0:28) Sarah and Stacy have done shows on the topic of marijuana and wellness, including CBD, CBD for pets, and pain management.  This show is sponsored by One Farm, both Sarah and Stacy's favorite CBD brands. One Farm's goal is to create the highest quality hemp extract on the market. Their products are made with the best hemp, grown organically in the perfect climate, extracted without toxic solvents, and mixed with quality ingredients. One Farm and their handling/processing facility are USDA Organic, which very few companies have. By controlling everything from seed to shelf, One Farm gives you the assurance that everything they make is from our USDA Certified Organic hemp, lovingly raised, cultivated, and processed 100% by One Farm in Colorado. Stacy notes that they also 3rd party test every batch that comes out of their USDA Certified lab. Use the code WHOLEVIEW at checkout to receive 15% off your order! Listener Question on Marijuana and Gut Health: Today's question about Marijuana and gut health comes from Dana (6:15): "I love focusing on gut health. I've read your books plus Dr. Terry Wahls books. I rely on cannabis to help me manage some of the residual MS symptoms I have while I work on healing my body. I am greatly aware of the risk of developing CHS as it has been on the rise in the Medical marijuana community here in Portland. It's terrifying to know that something that helps us so much, can harm us too. My question: How does THC affect the gut and gut motility? How can we prevent CHS medical users who use regularly and sometimes heavily to help manage our diseases? There isn't a lot of research I've found surrounding the effects of thc on the gut. I know it can slow down gut motility, but how much is too much and is there a way to counteract this effect? Does CBD have the same effect as thc on the gut or is it different? Can they work together in the gut to create a safer gut effect versus using a higher thc ratio? Ratios are big in the medical world. We rely heavily on the science we are presented in regards to the best ratios for our specific disease. There needs to be more talk on the potential risks of cannabis and how to lower our chances of developing something like CHS since so many of us meet the criteria of being at high risk of developing it. Would love to hear your thoughts on this. Seriously. Thank you."   CHS: Cannabinoid Hyperemesis Syndrome As Sarah explains, CHS is a very rare syndrome that occurs in long-term, heavy users of THC-rich cannabis. (7:50) It was only first reported in medical literature in 2004. The reported symptoms include nausea, vomiting, and abdominal pain. Also, they are episodic, lasting for 24 to 48 hours, and not returning for several weeks or months.   More than 90% of cannabis users who experience these symptoms also have a compulsion to bathe in hot water during the episode.  This is often what helps doctors and patients determine CHS as the cause. Sarah adds that vomiting can be severe and can leave CHS patients extremely dehydrated, acidosis, decreased serum bicarbonate, acute renal failure, and damage to the esophagus.  Because cannabis is usually known to help keep nausea and vomiting at bay, these users may end up using cannabis to keep the CHS symptoms at bay. Hyperemesis symptoms are very resistant, and typical antiemetics, such as ondansetron and promethazine, don't work. The treatment of choice is abstinence for a prolonged period. The only other effective treatment currently is IM injection with Haloperidol (normally used to treat schizophrenia, schizoaffective disorders, and Tourette syndrome) or Olanzapine (normally used to treat schizophrenia and bipolar disorder). Because of the use of antipsychotics, this suggests it's not working through the "normal" ways that induce vomiting. That it's something more related to the central nervous system and not the GI tract.   The Difference Between THC and CBD Sarah believes it's critical to look at the differences between THC and CBD to see why CHS is rising. (13:15) Both THC and CBD are plant chemicals that interact with the endocannabinoid system, an ancient lipid signaling system. It mediates between our emotional and physical reactions to pain.  THC is the most abundant chemical in cannabis. It's also the cannabinoid responsible for the sense of euphoria or "high" that comes from using the plant.  CBD is the second most abundant chemical and doesn't have the same psychoactive effects as THC.  The difference comes down to how each chemical binds with different receptors in our bodies and activates them. CBD binds but doesn't activate, which is why you don't get the same sense of euphoria as THC.  Instead, it appears to modulate or adjust how the receptors respond to stimulation from other compounds. THC creates mental status changes, motor function, memory, and body temperature by interacting with CB1 and CB2 receptors. This can manifest as euphoria accompanied by increased heart rate, anxiety, hunger, and eventually sleepiness. CBD CBD does not have psychoactive effects for most people or very weak effects on sensitive people. (17:30) Instead is associated with: Neuroprotective Anti-inflammatory Antioxidant Analgesic  Antipsychotic Anti-anxiety & antidepressant As we talked about in TWV Podcast Episode 420: CBD for Pain Management, both THC and CBD have been shown to reduce pain. Both CBD and THC also have strong antiemetic effects. Also, THC increases appetite and can have a sedating effect useful for insomnia. Because of the combo of increasing appetite and decreasing nausea, cannabis is often used by cancer patients when they're undergoing chemotherapy. High-THC Marijuana And Gut Health Stacy adds that the drug industry has actually altered these plants and bred them to yield higher THC concentrations. (20:01) The decreasing levels of CBD are an unintended consequence of that practice.  In the old days of finding wild marijuana, THC and CBD's typical levels would be about 50/50.  In the 1990s, typical "joints" contained 1–3 mg of THC. The typical joint in Colorado now contains 18 mg of THC or more. Also, Emergency room patients have self-reported smoking up to 2,000 mg or more of THC in a day. Higher potency products are associated with an increased risk for CHS and an increased risk for psychosis and other types of weed sickness, such as Cannabis Use Disorder. However, CHS is still considered a pretty care complication.   What Are the Chances of Developing CHS? About 75% of CHS cases report daily or more than daily cannabis users, most of the remaining use at least weekly, very few cases are less often than that. (25:50) Sarah adds that there aren't many good epidemiological studies out there right now. But there are a lot of case reports and series to look at for data.  About ⅔ of patients diagnosed with CHS have been using cannabis for at least 2 years before symptom onset. So far, CHS cases' demographics reflect the demographics of cannabis users, so it doesn't look like any particular population is at greater risk. So, this increase likely reflects increased use. A study that investigated trends of marijuana use between 2002 and 2014 indicated that prevalence is increasing among both men and women.  Data from the US national survey on drug use and health show that 12.4 million men and 7.7 million women used marijuana in 2002. This number increased to 18.4 million men and 11.7 million women in 2014.  Sarah notes that we're not quite sure why some people who use cannabis daily develop the condition and others don't. Current estimates are that 12% of Americans are active cannabis users. Another study showed that CHS sufferers had to seek medical attention an average of 7 times before getting diagnosed. Sarah does this quick math:  This would place CHS risk for near-daily to daily users of cannabis anywhere between about 0.2% and 1%. (1 in 100 to 1 in 500) The risk for more casual users would be much, much, much lower, using the same back of the envelope math, about 0.003% (1 in 30,000) A similar study in Colorado showed the incidence of CHS about doubled after legalization of cannabis. What Does It Mean? Medical marijuana is on the ride in many areas. Stacy wonders about the implications this could have on health. Sarah reminds listeners that this is very rough data. She did very rough math to give everyone a general idea of how common this complication. She also dug deep, looking for similar health issues caused by high-CBD use, and found one paper so far with very little data listed. Sarah found a narrative article that mentions it can very rarely be seen with high CBD use, but not a single published case study to look at. So, it's unclear if the claim is actually true. In fact, there's a postulation that increasing CBD could protect against CHS. The combination of high THC and low CBD in high-potency cannabis is driving whatever maladaptation is behind CHS. The Mechanisms Behind CHS Sarah explains that, so far, no good quality data pointing to exactly what is causing CHS.  Cannabinoids may bind to CB-1 receptors in the gastrointestinal tract and decrease GI motility and gastric emptying. This may override brainstem-mediated antiemetic effects and precipitate hyperemesis. [9, 92, 95, 132] Chronic cannabis use leads to desensitization and downregulation of CB1 receptors that ordinarily have peripheral antiemetic effects. This causes rebound vomiting and spasmodic pain that abates with abstinence and corresponding recovery of CB-1 receptor activity. [98, 136, 185] In chronic cannabis users, cannabinoid metabolites may accumulate in the brain and fatty tissues, inducing a toxic effect. [90, 94] Patients susceptible to developing CHS may have a genetic variation in their metabolic enzymes resulting in toxic levels of cannabinoid metabolites [131] THC may act as a partial agonist on CB1 receptors and thus relatively antagonize the effects of full endogenous agonists on these receptors. This would precipitate sudden withdrawal and hyperemesis in sensitive patients. [97, 105] THC causes dilation of splanchnic vasculature, resulting in CHS. Hot bathing leads to peripheral vasodilation and shunts blood away from the splanchnic bed, resulting in symptom improvement. [102, 137] Marijuana and Gut Health Stacy adds that if you live in an area where marijuana is legal, people who work in the shops that sell it are educated on the topics and can point you to what will work best for your needs. (46:30) Sarah underlines that she doesn't want this show to scare away anyone from using CBD that might benefit CBD. Results show normalization of overall appetite and increased/decreases in some circumstances. It also shows a reduction preference for fatty foods- especially polyunsaturated fats.  It's also believed to relieve diarrhea and abdominal pain, improve appetite in IBD, reduce inflammation and histamine in the gut, prevent mast cells from releasing histamine, and reduce intestinal inflammation in various models and humans. Data also suggests that THC and CBD's use improves gut barrier health and reduces intestinal permeability in a variety of models. The Gut Microbiome The blocking endocannabinoid system causes gut dysbiosis and endotoxemia. A 2015 mouse study showed THC reduced weight gain, fat mass gain, and energy intake in Diet-Induced Obese but not lean mice. This 2019 mouse study showed THC and CBD could improve experimental MS (reducing inflammation and clinical signs of paralysis) with effects at least partly mediated via improvements to the gut microbiome, preventing dysbiosis normally associated with MS. Another 2020 study used CBD plus fish oil in the mouse model of colitis and showed that CBD and fish oil had small benefits. However, both had additive benefits when used together, including reducing inflammation, reducing intestinal permeability, and improving the gut microbiome.  More of Sarah's Citations: Epidemiology of cannabis use: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719106/ https://www.cdc.gov/mmwr/volumes/65/ss/ss6511a1.htm Basics: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915118/ CHS Review articles: 2011 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576702/  2017 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330965/ 2019 https://digitalcommons.chapman.edu/physician_assistant_articles/6/ 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194425/ 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599351/ https://pubmed.ncbi.nlm.nih.gov/33208685/  2021 https://pubmed.ncbi.nlm.nih.gov/32673642/ Seems to be due to THC to CBD ratio: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690288/  CBD and Gut Health https://pubmed.ncbi.nlm.nih.gov/31803950/ https://pubmed.ncbi.nlm.nih.gov/33162890/ Inflammation https://pubmed.ncbi.nlm.nih.gov/31764093/ Cannabis https://pubmed.ncbi.nlm.nih.gov/27792038/ THC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669115/  Endocannabinoids https://pubmed.ncbi.nlm.nih.gov/27792038/  Gut barrier https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333598/   Final Thoughts When Sarah looks at all this data together, she definitely feels it's worth having a conversation with your healthcare provider if you're planning to use marijuana for medial purposes. (57:22) Sarah and Stacy are big fans of CBD for its diverse benefits. And that it doesn’t have the problems associated with chronic cannabis use. Thank you to One Farm for not only sponsoring this show but having a trustworthy and high-quality product.   Stacy adds that she's so appreciative of their third-party testing because that's not a practice that's regulated. If you've not yet joined the Patreon family and want to know how Stacy and Sarah really feel about this topic, hop over for more bonus content and stories. Thank you for listening!

This week, we discuss which agents to use to control agitation in a few different clinical scenarios encountered in the ER.Please click HERE to leave a review of the podcast!References:All references for Episode 45 are found on my Read by QxMD collection

Contributor: Don Stader, MD Educational Pearls: Zyprexa (olanzapine) is a second generation antipsychotic with multiple other uses Excellent for treating nausea in patients undergoing chemotherapy or with THC hyperemesis syndrome Helps with the psychological and emotional aspect of pain Effective in treatment of headaches Can be given under the tongue Fewer incidences of dystonic reactions compared with first generation antipsychotics Patients using anti-dopaminergic should not receive antipsychotics because they also work on dopaminergic receptors References Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. doi: 10.1056/NEJMoa1515725. PMID: 27410922; PMCID: PMC5344450. Jimenez XF, Sundararajan T, Covington EC. A Systematic Review of Atypical Antipsychotics in Chronic Pain Management: Olanzapine Demonstrates Potential in Central Sensitization, Fibromyalgia, and Headache/Migraine. Clin J Pain. 2018 Jun;34(6):585-591. doi: 10.1097/AJP.0000000000000567. PMID: 29077621. Summarized by Jackson Roos, MS4 | Edited by Erik Verzemnieks, MD The Emergency Medical Minute is excited to announce that we are now offering AMA PRA Category 1 credits™ via online course modules. To access these and for more information, visit our website at www.emergencymedicalminute.com/cme-courses/ and create an account.

If we trust the Catie trial, olanzapine is one the most effective antipsychotics for schizophrenia. Why? Despite its trying side effects – particularly weight gain--patients stuck with it the longest, which means it was doing enough good that patients were willing to stick with it despite any side effects it was causing. [Link] Published On: 11/21/2020 Duration: 2 minutes, 55 seconds Got feedback? Take the podcast survey.

Can biologics lower COVID-19 hospitalization risk in patients with psoriasis? Find out about this and more in today's PV Roundup podcast.

In this episode, we review the latest guidelines on antiemetics from the American Society of Clinical Oncology (ASCO). Host David H. Henry, MD, is joined by ASCO guideline author Paul J. Hesketh, MD, of Lahey Hospital and Medical Center in Burlington, Mass. Dr. Hesketh explains the recommendations for antiemetic use in cancer patients receiving checkpoint inhibitors (CPIs) or high-, moderate-, or low-emetic-risk antineoplastic agents. Checkpoint inhibitors The update to ASCO’s guidelines was primarily driven by questions about antiemetic use in patients receiving CPIs, according to Dr. Hesketh. After a literature review, Dr. Hesketh and coauthors concluded that: Patients receiving CPIs alone do not require an antiemetic regimen. When CPIs are given with chemotherapy, there is no need to modify the antiemetic regimen. Dexamethasone does not compromise the efficacy of CPIs. High-emetic-risk antineoplastic agents Adults treated with cisplatin and other high-emetic-risk single agents should be offered a four-drug combination: an NK1 receptor antagonist, a serotonin (5-HT3) receptor antagonist, dexamethasone, and olanzapine on day 1. Dexamethasone and olanzapine should be continued on days 2-4, as cisplatin can cause delayed emesis. Adults treated with an anthracycline plus cyclophosphamide should be offered a four-drug combination: an NK1 receptor antagonist, a 5-HT3 receptor antagonist, dexamethasone, and olanzapine on day 1. Unlike with cisplatin, only olanzapine should be continued on days 2-4. Olanzapine is an effective antiemetic in a number of settings, Dr. Hesketh said. For example, olanzapine is useful in the setting of hematopoietic stem cell transplant. A 5-mg dose of olanzapine has proven effective and may be better tolerated than a 10-mg dose. Moderate-emetic-risk antineoplastic agents Adults treated with higher-dose carboplatin (area under the curve ≥4 mg/mL per min) should be offered a three-drug combination: an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone on day 1. Adults treated with moderate-emetic-risk antineoplastic agents (excluding higher-dose carboplatin) should be offered a two-drug combination: a 5-HT3 receptor antagonist and dexamethasone on day 1. Adults treated with cyclophosphamide, doxorubicin, oxaliplatin, and other moderate-emetic-risk antineoplastic agents known to cause delayed nausea and vomiting may be offered dexamethasone on days 2-3. Low-emetic-risk antineoplastic agents Adults treated with low-emetic-risk antineoplastic agents (e.g., fluorouracil, gemcitabine) should be offered a single dose of a 5-HT3 receptor antagonist or a single 8-mg dose of dexamethasone before antineoplastic treatment. Cannabinoids There is no good data on the use of cannabinoids, apart from those cannabinoids approved by the Food and Drug Administration, according to Dr. Hesketh. The ASCO guidelines state: There is insufficient evidence to make a recommendation regarding medical marijuana to prevent nausea and vomiting in cancer patients receiving chemotherapy or radiation. Similarly, there is insufficient evidence to make a recommendation on the use of medical marijuana in place of the approved cannabinoids dronabinol and nabilone for the treatment of nausea and vomiting in cancer patients receiving chemotherapy or radiation. SOURCE: Hesketh PJ et al. J Clin Oncol. 2020 Aug 20;38(24):2782-97. https://bit.ly/3oxahUP Show notes written by Alesha Levenson, MD, a resident at Pennsylvania Hospital, Philadelphia. Disclosures: Dr. Hesketh disclosed institutional research funding from AstraZeneca and F. Hoffmann-La Roche. Dr. Henry has no relevant disclosures. * * * For information on the negative effects of marijuana, listen to our sister podcast, Psychcast, on MDedge (https://bit.ly/3mBM6TB), Spotify (https://spoti.fi/3mwVvvn), or wherever you get your podcasts. * * * For more MDedge Podcasts, go to mdedge.com/podcasts. Email the show: podcasts@mdedge.com. Interact with us on Twitter: @MDedgehemonc. David Henry on Twitter: @davidhenrymd.

Drugs discussed in this topic : AMOXICILLIN, LAMOTRIGINE , OLANZAPINE , LITHIUM TOXICITY, CLAVULANIC ACID

Olanzapine is a 2nd generation antipsychotic that blocks dopamine-2 receptors. Olanzapine Relprevv (long acting injectable) needs to be closely monitored after the injection is given due to risks of sedation and delirium. Sedation is a common occurance with the use of olanzapine. It is one of the more sedating second generation antipsychotics. Weight gain, hyperlipidemia, and hyperglycemia are all potential adverse effects with olanzapine.

We discuss a study on the use of the mu-opioid receptor antagonist, samidorphan for olanzapine-induced weight gain, compared to placebo and naltrexone. Earn 0.5 CME here Become a premium member of the Psychopharmacology Institute

Dr. Walter Kaye is a Professor in the Department of Psychiatry and the Founder & Executive Director of the Eating Disorders Program at the Eating Disorders Center for Treatment and Research at UC San Diego. Dr Kay is a leading expert in Eating Disorders and is a co-editor in the Clinical Handbook of Complex and Atypical Eating Disorders and the Behavioral Neurobiology of Eating Disorders. Dr. Kaye’s current research is focused on exploring the relationship between brain and behavior using brain imaging and genetics and developing and applying new treatments for anorexia and bulimia nervosa. Eating Disorders are severe disturbances in eating behaviors, thoughts and emotions. Many who suffer with eating disorders are preoccupied with both food and their weight. They can have severe body image dissatisfaction and a need for perfection. Even though eating disorders are grouped together in the DSM-5, they are distinct illnesses. Anorexia Nervosa symptoms include a distorted body image and a belief in being overweight despite being dangerously underweight. There are two types of anorexia nervosa, one restrictive and one binge-purge type. Bulimia Nervosa is characterized by eating excessive amounts of food in short period of time, and then purging the food using compensatory behaviors like vomiting and laxatives. Binge Eating Disorder is engaging in episodes of excessive eating, but unlike bulimia, there is not purging of the food or calories. Eating disorders affect people from all racial and ethnic backgrounds on many psychosocial levels. They can cause serious medical problems, and a multidisciplinary approach to care is needed.   Transcript Dr. Bridget Nash (2s): Hello, my name is Dr. Bridget Nash and I'd like to welcome you to the Therapy Show, a podcast series that seeks to demystify mental health treatment. Today I am honored to welcome Dr. Walter Kaye who is a Professor in the Department of Psychiatry and the founder and Executive Director of the Eating Disorders Program at the Eating Disorders Center for Treatment and Research at UC San Diego. Dr Kaye is a co-editor of the Clinical Handbook of Complex and Atypical Eating Disorders and Behavioral Neurobiology of Eating Disorders. He is a leading expert in eating disorders, and it's here to discuss some of the new research in the field of Treatment. Dr. Kaye welcome to the Therapy Show! Dr. Walter Kaye (42s): Oh, thank you very much. Dr. Bridget Nash (45s): Can you start by telling us a little bit about your personal background and professional development that led to your research in the field of eating disorders? Dr. Walter Kaye (53s): Yeah, certainly. I first trained as a neurologist and then trained in Psychiatry a number of years ago, and I've always been interested in doing research. I didn't particularly have an interest in eating disorders, but I got a fellowship at the National Institute of Mental Health, and when I went there I was asked to take over a study on Anorexia, and actually in my training I had never met anybody with Anorexia and at the time, I was particularly interested in trying to understand how behavior was encoded in the brain. Dr. Walter Kaye (1m 24s): And so, I was thinking about studying some disorders like Parkinson's that have certain changes in behavior, and we know that that's due to the neurologic disturbances in treating people with Anorexia. I was really struggling how, what we call it a stereotypic their behavior is, that it is people with Anorexia resemble each other much more so than probably any other psychiatric disorders in terms of people resembling each other. For example, if you have schizophrenia, people have all kinds of different symptoms. But people with Anorexia tend to have the same, relatively the same symptoms, and you know, that it can make you think that there is something in the brain that's causing this a, so that is actually been what got me interested in in studying brain and biology and Anorexia. I was at NIMH for about seven years, and then I went to the University of Pittsburg for 20 years, and now I'm here at a University of California, San Diego, where I do research and also, I oversee the treatment program for Anorexia and Bulimia.  Dr. Bridget Nash (2m 27s): So how would you briefly explain Eating disorders to a non-professional? Dr. Walter Kaye (2m 31s): This is a number of ways to explain it to it. I think that's what's really confuses people because people with the Anorexia often, but not all the time, they see themselves as being too fat and they go on a relentless pursuit of the thinness. And initially the other disorder that we treated very often is Bulimia Nervosa, which is where people are kind of alternate between restricted eating, overeating and then sometimes purging and people also have a body image distortion, but these are disorders that are often also associated with things like anxiety in obsessionality. Dr. Walter Kaye (3m 5s): And people have a certain time pattern of temperament traits. These tend to be perfectionistic, sometimes obsessive, anxious people. And so this has been very, very puzzling because the eating disorders, you know, tend to start mostly in females around early teenage or mid teenage years and so the prevailing notion is that this is a disorder of this caused by culture or society and people are dieting to achieve some kind of desired look. Dr. Walter Kaye (3m 39s): But the reality is that people with Anorexia diet to a weight that, they can be 50, 60 pounds, and and nobody would consider that to be fashionably slim. In fact, people with Anorexia, when they get to that weight, they still see themselves often as being too fat, and they want to pursue a lower weight. And the other thing that's really noticeable about Anorexia is that, it's very hard for people to diet or lose weight. The recidivism rate in obesity is very high and to be able to eat a few hundred calories a day, every day for years at a time is not something that most people can’t do. Dr. Walter Kaye (4m 21s): We've really been very interested in the question of whether it is really an underlying biology that explains a lot of these puzzling symptoms that you see in the Anorexia and Bulimia. Dr. Bridget Nash (4m 31s): Can you talk about what's happening in the brain and the body when a person has an eating disorder? Dr. Walter Kaye (4m 36s): Well, there's two levels of it. One is the question of whether there is some underlying biology that causes an eating disorder. And then the second part is, “gee what happens when you starve yourself and what effects does that have on their brain and the body.” Let's talk mostly about Anorexia cause that's really where I do most of my research. People with Anorexia go on this, this is kind of relentless diet and they may be 12, 14 and 15 years old when they start it. Dr. Walter Kaye (5m 7s): But if you ask somebody with Anorexia what they were like is a child before they ever developed the eating disorder, what most of the time they'll tell you is they have a certain pattern of temperament and personality traits. These tend to be as children they're very achievement oriented, or they want to get all A's. They tend to be often kind of perfectionistic. They may be anxious and worried about what might happen, concerned about risk, inhibited, sometimes very obsessional, and organized, sometimes kind of inflexible, but these are, for the most part, this isn't the problem for them. Dr. Walter Kaye (5m 44s): Their parents there pretty compliant kids. They do well in school. They are, but something happens when they start to get into these teenage years and often, they have exaggerated anxiety. And what they'll often tell you is, there something about food, or wanting to eat food that makes them very anxious, and something about not eating that either makes ... doesn't increase the anxiety or it actually feels kind of empowering. And so, they get into this, because food is so uncomfortable for them, that they get into this escalating downwards spiral where the more weight they lose, the more weight they want to lose, and they can literally starve themselves to death. Dr. Walter Kaye (6m 25s): In fact, this disorder has the highest death rate of any behavioral disorder. It's thought that somewhere between five or ten percent, maybe even more, people with Anorexia will die from the Anorexia. And so once you start to starve yourself and lose weight like this, there is a whole host of secondary changes that occur in the body as your body is trying to a conserve energy and live with very few calories and it effects nearly every organ system in the body as you lose weight. Dr. Walter Kaye (6m 56s): So, it's been very hard to tease apart what's the cause and what's the consequence of Anorexia. Now, over the course of this disorder, what we find is that a group of people recover and somewhere probably around about 50% of the people eventually recover and may do very well in life. But it's not unusual that people may be ill with Anorexia for two or five or even ten years before they get better. And about maybe about 30% or so have a partial recovery, and then you have a group of people that have very chronic disorder or die from it. Dr. Walter Kaye (7m 34s): And the thing that's really the most concerning thing to recognize is we don't really have very powerful treatments for Anorexia. There's no medication that's been proven to work. We have some treatments that seem to work more effectively in adolescents and children with the Anorexia, it's a, it's called Family Based Treatment or Maudsley, we can go back and talk a little bit more about that. But even with that treatment, it's very hard to change this anxious behavior that happens when people eat. Dr. Walter Kaye (8m 6s): And so it's very important to really understand the biology and the mechanisms underlying this behavior in order to come up with more effective kinds of therapy both to keep people from being ill for many, many years before they get better or to prevent them from becoming chronically ill or dying from this illness Dr. Bridget Nash (8m 28s): For Bulimia, can you talk a little bit about the body image symptoms? And also, is there a secondary gain that somebody might experience from binging and purging? Dr. Walter Kaye (8m 37s): Human behavior is complicated and, as similar as people with Anorexia are to each other, everybody's an individual, and there's probably always a mixture of different kinds of environmental and biologic factors that contribute to anybody developing a disorder like this. People was Bulimia -- why do people binge and purge --well people with Bulimia often tell you that when they're stressed or upset or anxious, have a fight with their mother or something like that, there is something about bingeing and purging behavior that actually is kind of comforting and may make the uncomfortable feelings go away, at least temporarily, even though in the long run they return and they may feel worse. So, they're, just like with Anorexia, there there's some beneficial response to extremes of food intake or extremes of not eating food, and now that we're beginning to understand more about the brain, some of the biology about this, begins to make sense. And with some people with Bulimia, because people with Bulimia often stay around the more normal weight, the body image issues that may be part of what's is also driving their desire to, to lose weight and to, to remain at a certain, what they consider ideal body weight. Dr. Walter Kaye (9m 58s): So, it's complicated, but again, most people with Bulimia don't get to the extremes of weight loss that you see with Anorexia. Then, of course, there's actually a third disorder here, which are people that have both a mixture of Anorexia and Bulimia and they lose a lot of weight, but they also binge and purge. Dr. Bridget Nash (10m 18s): Eating disorder behaviors are very secretive. Are there any signs or symptoms that a family can look for in the early stages of illness that can help them? Dr. Walter Kaye (10m 27s): You see two different kinds of patterns here. In people with Bulimia that don't lose an extreme amount of weight, they often tell you they're ashamed and a distressed about binging and purging. And they tend to be the most secretive. They're the people that nobody in the family will know that they're bingeing and purging, they're doing this at night, or they're hiding, or they're any number of things that people do to keep it a secret from their family. This may go on for years and sometimes it’s very hard to discover and the family begins to notice that there's large amounts of foods missing or that is a toilet has gotten clogged up by vomitus. Dr. Walter Kaye (10m 59s): You know one of the things that happens when people binge or purge to an extreme, it may affect their menstrual periods then they stop having a menstrual period or they may be very irregular. We see in a very different pattern in Anorexia and people with Anorexia don't usually try and hide it, they have more of a, a denial so that they don't see themselves as well being too thin. And in fact, even though they may lose 30, 40 pounds, they'll look at it their arm, you know, hold their arm out to say... Dr. Walter Kaye (11m 30s): "Can't you see how fat I am." And they're not really very motivated to get into treatment and there's a lot of denial and a lot of resistance to being in therapy and sometimes frank hostility to try to get them into treatment. And that's of course, one of the problems with Anorexia because it says it can be a life threatening illness. Yet this is a group of people that don't feel that they're at any risk. Dr. Bridget Nash (11m 56s): Why is the early intervention critical for people suffering with eating disorders? Dr. Walter Kaye (12m 0s): This goes back to a couple of different reasons. 1) There is there is some evidence that the earlier you get somebody into treatment, the better they might do. So, the most effective treatment we have, particularly for Anorexia, is called Family Based Treatment or Maudsley. And because this can be a very chronic disorder, and people get into treatment or are forced into treatment and forced to gain weight, but they leave treatment and they lose that weight all over again. Dr. Walter Kaye (12m 30s): And they may go through repeated cycles. So, because most families are unable to keep their child in a treatment program for a long period of time, and because this is a chronic disorder, this therapy has been effective because it makes parents an ally. Instead of saying to parents, you are bad people, you've caused this. There is really no evidence that families cause eating disorders or that bad parenting causes eating disorders. You want to bring them in as an ally and try to explain to them reasons why your child is acting this way, and more importantly make the parents part of the treatment team so once your child goes home, the parents have strategies and knows how to most effectively get them to eat and maintain their weight. And that treatment has really been a game changer in that there's a number of studies that have shown that is a more effective treatments for many people, especially if they’re younger than older treatments as usual. But say that there's a large proportion of people that don't really respond very well to Family Based Treatment and go on to have a chronic disorder. Dr. Walter Kaye (13m 33s): And so that's one of the reasons we need to learn more about the biology so that we come up with more effective approaches here. But what happens to people when they get malnourished? Well, there are certain systems in the body that growth during the teenage years is a very important, and so one of those is bone strength. And actually, your bones continue to develop and get stronger during your teenage years and your bone growth becomes peak in your late teens, early twenties, and then its, then you slowly lose strength as you get older. Dr. Walter Kaye (14m 11s): If you miss that are critical period of bone growth, you're gonna, your likely to have weak bones all your life. You cannot make up for it later with better nutrition when you're in their twenties and thirties. And it is not unusual that we see people who have had a period of Anorexia and now are fully recovered, but they suffer, they're very susceptible to fractures as they get into their thirties and forties that other people might not have just because their bones are so weak. And they're certain other patterns, similar kind of patterns of growth that occur in parts of the brain during your teenage years as you're are getting into your twenties. Dr. Walter Kaye (14m 48s): And now we're beginning to wonder whether there may be permanent changes to some parts of the brain if people remain malnourished for many years. There are long term consequences that can happen. And even people that have Bulimia Nervosa that don't lose a lot of weight can also show some of these more chronic permanent changes. Dr. Bridget Nash (15m 10s): I liked the way you talk about the family as part of the treatment team. And I think that a multidisciplinary approach is key to treating someone with an eating disorder, even including like when we think about it, the medical, the dental, the psychiatric in the psychotherapy piece, I think they're all critical don't you think? Dr. Walter Kaye (15m 30s): It takes the team to treat somebody with Anorexia. A dietician, a various kind of therapy, sometimes medication. Family is just maybe the most critical element of that whole team. Dr. Bridget Nash (15m 43s): What are some of the most common obstacles that prevent people from achieving a full recovery? Dr. Walter Kaye (15m 49s): I don't think we really know that. And that's where you start to get into biology. One of the questions that we've really struggle with, and typically are doing research on his, this question about eating behavior. Let me ask you, how, how do you feel when you go without eating for a day or two? Dr. Bridget Nash (16m 7s): Angry! Dr. Walter Kaye (16m 7s): Yeah. Most people will say there's something unpleasant about it. It's irritable. It's uncomfortable. It just doesn't feel good and what people will find, if you go without eating for a day or two, you you get hungry, that first bite of food really is more pleasurable. It will still be pleasurable. But when you are really hungry, food tastes better doesn't it? Dr. Bridget Nash (16m 28s): Yes. Dr. Walter Kaye (16m 30s): Okay. So, if you ask somebody with Anorexia, what do they feel like when they have to eat or they think about food, you know, what they almost always tell you is there's something about that that makes them anxious and uncomfortable. And when they don't eat, they feel the anxiety isn't increased, or sometimes they feel even better, empowered. So, just from that standpoint, it makes you think that there's something that is wired very differently in people's brain with Anorexia because the primary job of animals is to find food and feed themselves every day. Dr. Walter Kaye (17m 4s): And we know from animals’ studies there is very powerful systems that are built into the brain to do that. So, what happens is, when animals go without eating for a while, their body says to sense that they need energy stores, their energy stores are diminished, their gas tank is less full. And that, there's a number of different pathways from the brain that send the messages signals to the, to the brain that say "Gosh, you need more energy." And what that does is that really, you know, in humans that is interpreted as an uncomfortable feeling like: “Hey, there's something wrong, you got to go out and eat.” And in animals, what that particularly does is that works on a part of the brain that is very important for reward and motivation, and it actually sends a signal to that part of their brain that motivates you to go out and search for food. So, we know a lot about that part of their brain. It's very deep in the brain and is shared with animals. It's actually below our consciousness. It's a part of the brain that sits on top of the brainstem, but under the cortex and is called the striatum or the basal ganglia. Dr. Walter Kaye (18m 9s): And it’s very important for motivating all kinds of behavior, whether it's food or drugs or sex or anything that people or animals are motivated to do. And you can do brain imaging studies now that, at least, ask the question of – “What happens in that part of the brain, there's the activity in that part of the brain, that's important for motivation get turned on when you are hungry.” And so, we did a study in, and this is just published a couple of months ago in the American Journal of Psychiatry, where we had people with Anorexia come into a laboratory that we have on campus, building a setting. Dr. Walter Kaye (18m 45s): And they lived there for three days. One day we had them go without eating for 16 hours. On the other day we had to meet normally. And what we wanted to do is measure the activity in this motivational part of the brain. And so, we had them come in. Then after that the, they came into an imaging center and we imaged to their brain and we had them, we put a little plastic tube in their mouth we had them taste, repeat a taste of sugar water, which we know kind of turns on this system. And what we found is that, in the control women, the women that didn't have Anorexia, we found exactly what others have found. Dr. Walter Kaye (19m 20s): On the day that they were hungry, there was much more activity in this motivational center of the brain then there was on the day they were full. No surprise. And we did the same thing in people with anorexia, you know, what we found is that, on the day that if they were fed, they look just like the controls. On the day they were hungry, it was decreased activity in the motivation center. So. this makes perfect sense. It what is really saying is that people with Anorexia, the reason they can starve themselves is that they're just not getting a signal that's compelling them to go out and eat food. Dr. Walter Kaye (19m 59s): Does that kind of makes sense? Dr. Bridget Nash (20m 2s): It does. Now are they motivated to do anything else? Like to do other things like compulsive behaviors? Dr. Walter Kaye (20m 6s): We have looked at other kinds of motivation, which is things like response to money, and they had the same diminished signal in that part of the brain. So, you know, people with Anorexia like to save money, they don't spend money. And so, they are not really motivated to for any kind of reward, and that actually we think as part of the problem with treatment is that they really have a hard time sensing the reward of it. You know, parents try to motivate their kid's all the time to eat and maintain their weight by a promising "I'll buy you a new Porsche." Dr. Walter Kaye (20m 39s): Because treatment is so expensive, it's probably cheaper to buy them a Porsche and it doesn't work because the people with Anorexia tend to be very insensitive to reward. But the converse side of it is there over-sensitive to things going wrong, to what we call punishment or some kind of aversive risk state. In fact, it, the other thing that we found in this study is that the more anxious than people with... Anorexia were, the more activity they showed in this part of their brain that's very sensitive to things going wrong and inhibit behavior. Dr. Walter Kaye (21m 15s): And actually what we think is going on is that if you're an animal out there in the wild, you're a rabbit, your living out there in their field, you are living here in your little hole on the ground, is relatively safe, you start to get hungry, that hunger is going to motivate you to go out and look for food, right? But animals have to have a system built into their brain that inhibits that behavior if there's something dangerous going on like a predator that might eat it. And so even though that rabbit is very hungry, that rabbit has to inhibit that hunger and motivation to eat and run away if there's some kind of risk going on, some kind of danger. Dr. Walter Kaye (21m 54s): And what I think is going on with the people with Anorexia is they are getting kind of a biased signal here. They're over sensitive to things going wrong, danger, anxiety, adversity, change, uncertainty. All those things that give you a signal there's some kind of risk, and they're actually getting a signal in their brain. They're somehow miscoding food and their miscoding food is being dangerous and risky. And that doesn't exist for the rest of us because nobody is wired that way, but there's something very different about the brain that people with Anorexia. Dr. Walter Kaye (22m 28s): Does that kind of make sense. Dr. Bridget Nash (22m 31s): It makes a lot of sense. I just wonder what the cause is. Do you have any theories of the cause of where that began? Dr. Walter Kaye (22m 38s): Well, now that we're beginning to understand what system is involved in the brain, we think that there's something wrong in this mechanism that balances reward and punishment, and people with Anorexia tend to be very sensitive to punishment and risk and things like that. So, then what exactly is it a chemical mechanism of that is still a mystery, but I think we've started to understand were to look now. Dr. Bridget Nash (22m 60s): That's really hopeful and promising. So, is there anything that improves treatment outcomes? Dr. Walter Kaye (23m 6s): We're finding that some people, and there have been some articles now in the literature, part of this system, it relies on a chemical called dopamine, which actually, people think of it as a reward chemical, but it’s actually a very important for this balance between reward and punishment. And that there's some studies suggesting at at least some people with Anorexia, may respond to some drugs that work on the dopamine system. It was a paper on American Journal last year is showing that Zyprexa also called Olanzapine showed improved weight gain to some extent in people with Anorexia. Dr. Walter Kaye (23m 42s): And there's been several other studies showing that a drug called Abilify which kind of has a similar mechanism or Aripiprazole also might work on some people, it doesn't work in everybody, it's not a magic bullet, but it may be helpful to some people. We really need to do now more controlled studies of that. But at least it’s starting to open the door to ask questions about mechanisms, Oh, by the way, I wanted to mention one other thing. The thing that's really important about this study I just told you about is we studied people who had recovered from Anorexia and not people that were ill. Dr. Walter Kaye (24m 16s): And the reason that we did that is this problem with teasing apart cause and effect. If you study people are ill or malnourished with Anorexia, it wouldn't be surprising you'd get altered signals in his system, and we wanted to look at people that are normal weight, not on a medication, normal menstrual function, doing really well in life and we found that they still had a disturbance in this system and suggesting that this may be the trait that leads to Anorexia in the first place. Dr. Bridget Nash (24m 48s): Are there other mental disorders that often co-occur with eating disorders? Dr. Walter Kaye (24m 52s): Sure. One of the, it seems to be the most common is anxiety or Obsessive Compulsive Disorder, but people also have depression and they may have a number of other disorders too. Dr. Bridget Nash (25m 5s): So, do people with eating disorders have a higher rate of suicide? Dr. Walter Kaye (25m 8s): Unfortunately, they do. I mean that's part of the increase death rate and mortality rate in Anorexia is some people starve themselves to death, but some people commit suicide and another reason why we need more effective treatments. Dr. Bridget Nash (25m 24s): Why is it important that clinicians who are treating people with eating disorders are trained in the most up-to-date research and treatments? Dr. Walter Kaye (25m 32s): Just because of the difficulty of treating this disorder and the difficulty of even getting people to participate and engaged in treatment. The more we learned about the Anorexia and the symptoms that people have, I think the better we can speak peoples, the language in the way, you know, understand the way people are thinking and reach out to them and get them to be motivated and engage in treatment, and I think one of the problems that we've had with Anorexia and often psychiatric disorders, is that, do you try, and there's theories about behavior... Dr. Walter Kaye (26m 7s): and maybe they make a lot of sense, but maybe they don't, and if you try and use a theory, that really has no particular, it doesn't fit or explain why somebody has a disorder, it is less likely to result in any kind of effective therapy. So, for example, now that we understand this altered balance between reward and punishment, we can work with families on that strategy, and we explain this to families and say: "Look, rewarding your child isn't going to be that effective." But there are these are kids that worry about consequences and don't want to do things wrong or make mistakes or... Dr. Walter Kaye (26m 44s): and we can help families develop strategies to use consequences. Now we're not trying to punish their kids, it's just that, ya know, sometimes they pay much more attention to that and to realize that, if they don't eat and maintain their weight, there is going to be consequences they consider even worse, then it becomes very individualized cause you want to figure out what consequences bother that child the most. What we are finding that can be somewhat a more successful kind of strategy. Dr. Bridget Nash (27m 13s): That's incredible. So, to use consequences to get the attention and to sort of start the conversation with the young person or whoever you're treating, that's excellent. Dr. Walter Kaye (27m 23s): For example, kids with Anorexia, you know, they really don't want to go back into treatment, they don't want to go into the hospital, they don't want to go into, you know, a residential program and sometimes that's the only leverage that you have. Not great, but you have to work with what you got it. Dr. Bridget Nash (27m 38s): And I think if you're not trained in understanding eating disorders, I want to ask you to explain to our audience, eating disorders are different. They're almost like distinct disorders, like Bulimia is a distinct disorder and Anorexia nervosa are distinct disorders, I mean we call them all feeding disorders, but their complex and they're different. Dr. Walter Kaye (27m 57s): They're both very different and they actually, sometimes have some similarities and one of the puzzling things is that both the Anorexia and Bulimia run in families, so one person can have Anorexia and another can have Bulimia you know, I don't think we really, you understand this. Dr. Bridget Nash (28m 14s): And if you're a clinician who's working in the field, who's been certified and I think you also understand that some people need multiple treatment, multiple treatment center or multiple residential treatment... Dr. Walter Kaye (28m 25s): Yeah. Dr. Bridget Nash (28m 26s): ... to get better. Whereas the person who's not experienced might see that as they're failing or they're not getting it the first time. Can you speak to that a little bit? Dr. Walter Kaye (28m 35s): Yeah. Well, you know, one of the things that's very important is that when people get malnourished, they actually, their symptoms tend to get worse and they spiral out of control and they have difficulty. The brain gets starved. They have difficulty learning things or using therapy, and, and so for both mental as well as physical reasons, they need to get back to a healthy body weight and that can really be an enormous challenge for people with Anorexia, and so being an a, you know, they often end up a higher level of care because it’s just so, if you don't get them until a more healthy nutritional state, they may die from their Anorexia. Dr. Walter Kaye (29m 13s): And also, the other thing that's going on here is that some people with Anorexia get very energy inefficient. And by that, I mean there's been studies showing, for example, people with obesity, have a hard time losing weight and they seem to have an easy time gaining the weight back after they lose weight. The opposite tends to seem to occur with a lot of people with Anorexia. They lose weight very easily, and it's hard for them to gain weight. Dr. Walter Kaye (29m 43s): And sometimes they need thousands of calories a day to gain that weight back. And if you're somebody with Anorexia and you want to eat 500 calories a day and you need three or four thousand to gain weight, you know, two, three pounds a week, food is making you anxious, what's the chance they're going to be able to do that at home? Not great. And they may have to eat that amount of food for two, three, four months to get back to a healthy body weight. Dr. Walter Kaye (30m 13s): So sometimes higher levels of care are just so critical to save their life. Dr. Bridget Nash (30m 19s): Exactly. Now aren't people with Anorexia nervosa interested in food? I mean, I think there's a misconception that they're not interested in food, but do you think that they might have a preoccupation with food perhaps? Dr. Walter Kaye (30m 32s): Absolutely. I mean, they collect calories. They cook for others. They window shop for food. They work in food industries. And I think this has been one of the puzzling parts. So, this network, you can have a brain circuit that is very important for recognizing you're hungry and driving the motivation to eat. And there's a series of kind of steps along the way that do that. And it's possible that you could have a blockage in one part of that which is... Dr. Walter Kaye (31m 2s): So, people with Anorexia seem to recognize that they're hungry, they're getting the signal, they can't turn that signal into motivation to eat, to initiate eating. But they're still, their part of their brain is still recognizing they're hungry. And this is a strange signal that nobody else has, and I suspect that really explains why they're obsessed with food and they cook for others, yet they can't eat. Dr. Bridget Nash (31m 31s): And can you speak a little bit about Binge Eating Disorder. It's a new disorder in the DSM-5, but I think it's one that has a lot of medical consequences. Dr. Walter Kaye (31m 39s): Yeah. Binge Eating Disorder tends to occur more frequently in males. It's a somewhat later age of onset and people have, they tend to often have mood and anxiety disturbances and respond somewhat differently to treatment and other treatments compared to Anorexia, but ideologically they're really not the same disorder whereas you see, Bulimia nervosa and Anorexia nervosa kind of run together in families, you don't really see that; Binge Eating Disorder has a separate kind of family and inheritance structure. Dr. Walter Kaye (32m 13s): There's one other disorder that we've recognized now that it's ARFID, or Avoided Restricted Food Eating Disorder, which is very extreme, picky. It tends to occur in children, that's something that we treat a lot also. And these are kids, there is a whole host of different symptoms they have. Some have pain in their stomach and can't eat because it causes pain and some are very anxious, some have obsession, they only can eat four different white foods, some disturbed by certain textures and tastes of food. Dr. Walter Kaye (32m 43s): So, it's not just one symptom complex - it's something that we've more recently kind of recognized, and some of these children really have a hard time eating and lose a lot of weight and so it's one of the disorders that we treat. And there's some from these children who end up developing Anorexia and some just have an ARFID disorder, so it's things that we're learning about, but it's also a disorder where Family Based Treatment is often very useful. Dr. Bridget Nash (33m 10s): And early intervention as well. Dr. Walter Kaye (33m 12s): Yeah. Yeah, exactly. Yeah. Dr. Bridget Nash (33m 14s): What are you most excited about mental health treatment today? Dr. Walter Kaye (33m 18s): Well, you know, I think we're finally becoming a science. The progress that's been made in the last 10, 20 years has just been enormous. And of course, the reason was that the brain is encased in your skull there, as opposed to having diabetes or heart disease where you can measure things. We haven't been able to measure what's going on in the brain and it's only been the last decade or so we've had powerful brain imaging and genetics kinds of studies that are allowing us to really look inside the brain and begin to understand brain circuits and pathways and mechanisms of behavior and how behavior is encoded in the brain... Dr. Walter Kaye (33m 54s): that have just made a difference. I am just kind of astounded how far we've gotten in my professional career, where you can begin to look at these behaviors and go like "Oh, well I think this part of the brain is involved and now I understand the mechanism, and I can predict what we are going to find and we can replicate those kinds of findings." And that's starting to lead to more effective treatments as we begin to translate that science into therapy. Dr. Bridget Nash (34m 18s): Effective and targeted treatments as well. Dr. Walter Kaye (34m 24s): Yeah. And that's one of the things that we do here. I like to look at our program not only as a, a treatment program, but also a laboratory for developing treatments. So we've very interested in this whole question of temperament in people with Anorexia and you know, these temperaments don't go away, but people with Anorexia when they recover, tend to do really well in life and they learn to use some of these temperaments in really kind of advantageous ways. This is a group of people who were very achievement oriented. Dr. Walter Kaye (34m 53s): They self-discipline, they pay attention to detail. They work hard. They wanted to do the right thing and they often have not just great but have actually spectacular careers. And so, this actually turns out to be a benefit to having some of these traits once people learn to use them in advantageous constructive ways. So, we think that that may be actually an important insight into developing more effective treatment approaches. Dr. Bridget Nash (35m 25s): That is very exciting. If you had a magic wand and could improve one thing about mental health treatment today, what would it be? Dr. Walter Kaye (35m 31s): Being able to understand each person's unique vulnerabilities and mechanisms because when you really come down to it, people are pretty complicated and everybody has probably in some ways unique mechanisms that are causing, and environmental influences and so that starts to explain why, whatever treatment we have works for some people, but not others. And so, if we could better understand, you know, it's called precision medicine. If you can better understand each person's unique with a series of factors, you could really more precisely prescribe treatment. Dr. Walter Kaye (36m 6s): We're not there yet. It's going to be a while. Yeah. We'll probably get there. Dr. Bridget Nash (36m 12s): No, we're going to get there because people are going to be asking for it now. Like when we hear from you and hear all of these exciting targeted treatments, it's going to kind of create a demand. Do you think? Dr. Walter Kaye (36m 25s): Yeah, yeah, absolutely. Dr. Bridget Nash (36m 28s): Dr. Kaye on behalf of myself, my listeners, and all of the people that you've helped through your work. I want to thank you for your contributions to mental health treatment and for taking the time out of your busy schedule to help me and my audience better understand the field of eating disorders. And to my listeners, be sure to check out my website TherapyShow.com, which has many resources about mental health. There, you will also find how to submit questions, stories, or insights that you have about the mental health system or suggestions about who else I interview can and how I can improve the show. Dr. Bridget Nash (37m 1s): I'd like to close by reminding our listeners to please subscribe, share, and review this podcast. So you, someone you love, and people around the world can gain more benefit for therapy. There is no need to suffer in silence. Get the help that you need to create the life that you want.

In this episode, we discuss the use of droperidol for the treatment of agitation in the ER setting. Please remember to subscribe to our podcast and leave us a comment! References:Knott JC, et al. Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. Ann Emerg Med. 2006; 47: 61-67Isbister GK, et al. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med. 2010; 56: 392-401Chan EW, et al. Intravenous droperidol or olanzapine as adjunct to midazolam for the acutely agitated patient: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med. 2013; 61: 72-81Taylor, DM, et al. Midazolam-droperidol, droperidol, or olanzapine for acute agitation: a randomized clinical trial. Ann Emerge Med. 2017; 69(3): 318-326Olanzapine (Zyprexa) [prescribing information]. Princeton, NJ: Sandoz; 2019

Contributor: Sam Killian, MD Educational Pearls: Agitation can be due to a number of causes, but regardless of the cause, sedation often plays a key role in patient and provider safety. But what is the best sedative agent? A study looked at control of agitation with intramuscular medication. Specifically, 5 different IM sedative agents were compared to see which one best provides “adequate” sedation in 15 minutes or less. Haldol 5mg, Haldol 10mg, Versed 5mg, Zyprexa 10mg, and Geodon 20mg were all compared, and by far Versed provided the best sedative results. All medications had approximately the same amount of adverse effects. There are so many sedative options, but time and time again large dose benzodiazepines have demonstrated great effectiveness in treating acute agitation References 1) Klein, Lauren R. et al. Intramuscular Midazolam, Olanzapine, Ziprasidone, or Haloperidol for Treating Acute Agitation in the Emergency Department. Annals of Emergency Medicine. 2018. 72(4), 374 - 385   Summarized by Jackson Roos, MS3 | Edited by Erik Verzemnieks, MD

Contributor:  Don Stader, MD Educational Pearls: Olanzapine (Zyprexa) is an atypical antipsychotic that can be used in a similar fashion to haloperidol for pain and nausea, including that with abdominal pain and headaches Olanzapine can be administered as an oral disolving tablets, intramuscular or intravenous injection Because Zyprexa is an atypical antipsychotic, it has a lower risk for tardive dyskinesia and akathisia  Olanzapine may cause transient rises in glucose and should be considered when contemplating use in a diabetic References Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults.Sutherland A, Naessens K, Plugge E, Ware L, Head K, Burton MJ, Wee B. Cochrane Database Syst Rev. 2018;9:CD012555. Epub 2018 Sep 21.  Silberstein, S.D., Peres, M.F., Hopkins, M.M., Shechter, A.L., Young, W.B. and Rozen, T.D. (2002), Olanzapine in the Treatment of Refractory Migraine and Chronic Daily Headache. Headache: The Journal of Head and Face Pain, 42: 515-518. doi:10.1046/j.1526-4610.2002.02126. Summarized by Will Dewispelaere, MS4 | Edited by Erik Verzemnieks, MD

Zyprexa, also known as Olanzapine, is a drug typically used to treat mental illnesses such as schizophrenia and bipolar disorder.  I have been on it since I first was put on medication.

We are at ACEP 2019 in Denver and do a deep dive on a topic introduced by Bryan Hayes (@PharmERToxGuy) in a talk on black boxed medications used in the ED. We review the data underlying the FDA warning for olanzapine and benzodiazepines. Thanks for listening! Jeremy Faust and Lauren Westafer

Author: Jared Scott, MD Educational Pearls: Study from Hennepin County EM studied the efficacy of different drugs for agitation, which included 737 patients Most patients in this study were male and *surprise* drunk Compared doses of common sedatives with primary outcome of sedation at 15 minutes (all intramuscular) haloperidol 5 mg ziprasidone 20 mg olanzapine 10 mg midazolam 5 mg haloperidol 10 mg with the main outcome of agitation at 15 minutes Intramuscular midazolam resulted in the lowest level of agitation at 15 minutes, followed by ziprasidone. There were no differences in adverse effects. References Klein LR, Driver BE, Miner JR, Martel ML, Hessel M, Collins JD, Horton GB, Fagerstrom E, Satpathy R, Cole JB. Intramuscular Midazolam, Olanzapine, Ziprasidone, or Haloperidol for Treating Acute Agitation in the Emergency Department. Ann Emerg Med. 2018 Oct;72(4):374-385. doi: 10.1016/j.annemergmed.2018.04.027. Epub 2018 Jun 7. PubMed PMID: 29885904. Summarized by Will Dewispelaere, MS4 | Edited by Erik Verzemnieks, MD

August 20, 2019 edition of the weekly JAMA Editors' Summary

  This month on the Discover CircRes podcast, host Cindy St. Hilaire highlights three featured articles from recent issues of Circulation Research and talks with Denisa Wagner and Nicoletta Sorvillo about their article on how PAD4 in blood promotes VWF strings and thrombosis. Article highlights: Goodyer et al: ScRNA-seq of the Cardiac Conduction System   Xiong et al: Chemotaxis Mediated Second Heart Field Deployment   Ranchoux et al: Pulmonary Hypertension and Metabolic Syndrome   Rühl et al. Thrombin/APC Response in FVL and FII 20210G>A   Mahmoud et al. LncRNA SMILR’s Mechanism and Therapeutic Potential   Transcript   Cindy St. H:                         Hi, welcome to Discover CircRes, the monthly podcast of the American Heart Association's Journal, Circulation Research. I'm your host, Cindy St. Hilaire, and I'm an assistant professor at the University of Pittsburgh. My goal as host of this podcast is to share with you some highlights from the recent articles published in the August 2nd and August 16th issues of Circulation Research. Cindy St. H:                         After I discuss some highlights, we'll also have an in-depth conversation with Drs. Denisa Wagner and Nicoletta Sorvillo, from Boston Children's Hospital and Harvard Medical School, who are the lead authors of one of the exciting discoveries from the August 16th issue. Cindy St. H:                         The first article I want to share with you today is titled Transcriptomic Profiling of the Developing Cardiac Conduction System at Single-Cell Resolution. The first author is William R. Goodyer, and the corresponding author is Sean Wu. They are both located at the Cardiovascular Institute and the Department of Pediatrics at Stanford University. Cindy St. H:                         Have you ever wondered how your heart beats, and why there's always this glub-glub pattern, and where did it come from? How is the heart able to initiate that pattern, from cells that don't contract to cells that contract? Well, the beating of the heart is regulated by what's called the cardiac conduction system, and this is an area in the heart of specialized cells, and these cells establish the rhythmic beating by coordinating the contraction of the chambers of the heart. Cindy St. H:                         There's several components to the CSS. The sinoatrial node acts as the pacemaker in the right atrium. The arterial ventricle node is the electrical relay that slows down the pulse from the SA node. A His bundle helps to transmit those impulses, and the Purkinjie fibers are the terminus of the electrical signal. Between all of these different components are a heterogeneous population of what are called transitional cells. There are several studies that have linked these somewhat amorphous or heterogeneous transitional cells to different arrhythmic disorders. Cindy St. H:                         For the normal function of the heart, all of these parts must come together, and when they don't, there's severe clinical manifestations such as arrhythmias, like I said, but also you can get decreased cardiac output and even sudden cardiac death. While important, the cells of the CSS are rather elusive, and that's because they're in a relatively small number compared to the rest of the cells in the heart, and there also aren't very clear markers to identify the cells in the CSS. Cindy St. H:                         To address this, Goodyer and colleagues harvested cells from embryonic mouse hearts and performed single-cell RNA sequencing on 22,000 individually barcoded cells. What they were looking for is learning what type of cells they are, but more importantly, they had the goal of identifying what these elusive transitional cells are, and can we find a marker for these cells to study them? And in some, yes. Together, the sequencing and spatial data provided gene expression atlas of the mouse CSS. Hopefully, this atlas will guide future studies into the essential electrical system that regulates the heartbeat. Cindy St. H:                         The next article I'd like to highlight is titled Single-Cell Transcriptomics Reveals Chemotaxis-Mediated Intra-Organ Crosstalk During Cardiogenesis. We're really going to hit you over the head with some single-cell transcriptomics in this month's podcast. The first authors of this article are Halqing Xiong, Yingjie Lou, Yanzhu Yue, Jiejie Zhang and the corresponding author is Aibin He and they're all from the Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine and the Peking-Tsinghua Center for Life Sciences, all at Peking University in Beijing, China. Cindy St. H:                         During development, the mammalian heart originates from two distinct areas in the early embryo and they're called the first heart field and the second heart field. Progenitor cells from these regions give rise to very different structures. From the first heart field comes the atria and the left ventricle, and the second heart field forms the right ventricle and the outflow tract. While we know the outcomes of these different developmental layers, a full understanding of how the first and second heart fields are regulated and how they actually interact with one another is actually lacking a lot of detail and we're not exactly sure how those structures can influence one another. Cindy St. H:                         So to learn more, Xiong and colleagues utilized two different murine models that were engineered to label cells coming from either the first or second heart fields red, and by labeling these cells red, it allows for their very pure isolation and then downstream studying at the single-cell level. So from each of these two models, they collected about 600 red-labeled cells and they collected these cells at four different time points, that were essentially at 12 hour intervals, and they did this starting at embryonic day 7.5, and that's because that's the time point in the mouse where these second and first heart fields are starting to develop. Cindy St. H:                         What they found, by using single-cell RNA sequencing, is that the first heart field cells differentiated into cardiomyocytes, in what they called a gradual, wave-like manner, while the second heart field cells differentiated in what they referred to as a more stepwise, defined pattern. The team also found high expression of migration factor MIF in first heart field cells and they found MIF's receptor CXCR2 in the second heart field progenitor cells. This suggests that perhaps the first heart field cells could regulate the migration of the second heart field cells. Sure enough, blocking MIF- CXCR2 interaction in cultured mouse embryos prevented second heart field cell migration and also prevented normal development of the right ventricular outflow tract structures. So together these results provide insight into both normal heart development and also suggest what might go awry in certain congenital heart malformations. Cindy St. H:                         The next paper I want to highlight is titled Metabolic Syndrome Exacerbates Pulmonary Hypertension due to Left Heart Disease. The first author is Benoit Ranchoux and the corresponding author is Francois Potus, and they are from the Pulmonary Hypertension Research Group at Laval University in Quebec City in Quebec, Canada. The disease pulmonary hypertension can arise from a number of causes, but one of the main drivers of what's called group two pulmonary hypertension is left heart disease. Left heart disease itself is caused by several conditions, such as diastolic dysfunction, aortic stenosis, which is a disease that I study, or mitral valve disease. All of these pathologies result in the left heart not beating efficiently or exerting too much energy. Cindy St. H:                         More than half of all group 2 PH patients also have metabolic syndrome, and metabolic syndrome is a condition that is ever increasing in the modern age, especially in America, and it's characterized by obesity coupled with pathology such as dyslipidemia, type 2 diabetes and high blood pressure. Metabolic syndrome is also marked by elevated levels of the inflammatory cytokine IL6. Rat studies have shown that IL6 can induce proliferation of the pulmonary artery smooth muscle cells and consequently, pulmonary hypertension. Cindy St. H:                         In this study Ranchoux and colleagues pulled together all these different pieces in a rat model and essentially want to test left heart disease coupled with metabolic syndrome coupled with does pulmonary hypertension happen or get worse? What they found was really interesting. Left heart disease was induced in a rat model using super coronary aortic banding and then metabolic syndrome was induced with a high fat diet feeding, or with treatment with Olanzapine, which is a second generation anti-psychotic agent, and it's known to induce metabolic syndrome not only in rats, but also in humans. The data from this paper show that inducing metabolic syndrome in rats coupled with left heart disease resulted in elevated IL6 levels and also greatly exacerbated pulmonary hypertension. Cindy St. H:                         Digging into this mechanism, they found that inhibition of IL6, using either an anti-IL6 antibody or by reducing IL6 secretion from macrophages, using the diabetes drug Metformin, ameliorated the pulmonary hypertension in the rats. They then went on and looked at human samples and they found that IL6 was higher in the lungs of pulmonary hypertension patients and that this IL6 could induce proliferation of human pulmonary artery smooth muscle cells. So together these data suggest that the observation in rats holds true for humans, but further goes on to suggest that perhaps Metformin, which is a well-known, well-used diabetic drug, could perhaps be used for the potential treatment of Group 2 pulmonary hypertension patients.   Cindy St. H:                           In the August 16th issue, we have an article titled Increased Activated Protein C Response Rates Reduce the Thrombotic Risk of Factor V Leiden Carriers but not of Prothrombin 20210G>A Carriers. That is some title. The first authors are Heiko Rühl, and Christina Berens, and Dr Rühl is also the corresponding author, and they are at the Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, in Bonn, Germany. Genetic studies have found two mutations that convey particularly increased risk for venous thrombo-embolism, and VTE is also more commonly referred to as deep vein thrombosis. These mutations are called factor five Leiden mutations, or FVL, and the prothrombin 20210G>A mutation we're just going to call F2. Interestingly, the penetrance of these mutations, or how likely they are to exhibit a phenotype, is variable. Some individuals with mutations never experience deep vein thrombosis, while others experience multiple episodes. Cindy St. H:                         As a group, the FVL carriers produce a higher than normal level of an anticoagulation factor called APC, or activated protein c. They also produce high levels of the pro-coagulation factor thrombin, and the authors of this study wondered if it was the balance, or rather perhaps an imbalance, of these factors that could explain the phenotypic variations in the patients that harbor the same mutation. To test this, they collected 58 patients. 30 were FVL and 28 were F2 carriers, and they injected these patients with clotting factors and examined their response rates. In both of the groups, about half of the individuals had no history of deep vein thrombosis, while the other half had had at least one episode. Cindy St. H:                         The team found that while both types of mutations were associated with increased APC and thrombin levels after coagulant injection compared with a control group, in the FVL group lower APC levels correlated with a much higher risk of deep vein thrombosis. In other words, the FVL carriers who had never experienced deep vein thrombosis produced higher levels of APC. Translating this to the clinic, perhaps APC testing could help identify individuals who are carriers of the FVL mutation and determine which of them are at higher risk due to lower levels of APC. Cindy St. H:                         The last paper we're going to highlight before switching to our interview is titled The Human- and Smooth Muscle Cell Enriched lncRNA, SMILR, Promotes Proliferation by Regulating Mitotic CENPF mRNA and Drives Cell Cycle Progression Which Can Be Targeted to Limit Vascular Remodeling. Now that is a crazy title! We’ve got to limit these names here this is difficult. The first authors are Amira Mahmoud and Margaret Ballantyne and the corresponding author is Andrew Baker, and they're all from Queens Medical Research Institute, BHF Center for Cardiovascular Sciences at University of Edinburgh in Edinburgh, UK. Cindy St. H:                         Before we dive into this article, I think it's important that we give a quick explanation of what is a lncRNA? lncRNA, or L-N-C RNA, stands for long non-coding RNA, and these are described as being transcripts which are made into RNA that are in lengths exceeding 200 nucleotides. So that differs them from micro RNAs or peewee RNAs or snRNAs, and they are classically or, I guess originally, considered not to be translated into protein. However, I think now more and more studies are finding that perhaps they are made into peptide sequences. However it's not fully clear what the function of those sequences are. Similar to micro RNAs, they also harbor regulatory functions that can control cellular functions by helping to fine tune the regulation of gene transcription and translation. Cindy St. H:                         Largely speaking, vascular smooth muscle cells are quiescent, but they can be stimulated to proliferate and migrate following injury to the vessel wall. While such activation of smooth muscle cells is essential for wound healing, these same processes are operative in vascular disease or after a cardiovascular procedure. Often what happens is an excess of proliferation of the smooth muscle cell wall can lead to dangerous occlusion of the blood vessel. The long non-coding RNA, SMILR, was recently identified as a promoter of smooth muscle cell proliferation and now in this article, Mahmoud and colleagues have defined its mechanism of action. Through transcriptome analysis of human smooth muscle cells, in which the levels of SMILR were either modulated to be increased or suppressed, the team found that lncRNA regulated expression of several genes involved in mitosis, or cell division. Furthermore, RNA interaction experiments revealed that the messenger RNA encoding the mitotic centromere protein, CENPF, was a direct interaction partner of SMILR. So just like the suppression of SMILR, the inhibition of CENPF resulted in reduced mitosis of the smooth muscle cells. Cindy St. H:                         The team then went on to show the inhibition of SMILR via RNA interference could block the smooth muscle cell proliferation ex-vivo, and they did this using intact sections of human saphenous vein. These results suggest that targeting this lncRNA could be a potential clinical treatment in situations where vessel occlusion is at risk. Cindy St. H:                       Okay, so now we're going to switch and have our interview with Drs Denisa Wagner and Nicoletta Sorvillo, and we're going to discuss their paper entitled Plasma Peptidylarginine Deiminase IV Promotes VWF-Platelet String Formation and Accelerates Thrombosis after Vessel Injury. Thank you Drs. Wagner and Sorvillo for joining us today. I think a funny thing is that between Nicoletta in Switzerland, me and you on the East coast and my producer on the West coast, I think we're spanning about nine hours of time zones here. Thank you all for taking the time, whatever time of day it is, wherever you are. Dr Wagner:                         Thank you. Cindy St. H:                         I was wondering, Denisa, if you could please introduce yourself and tell us a little bit about your background. Dr Wagner:                         I am a vascular biologist. I was always interested in platelets, endothelial cells, and leukocyte. I started with a background of von Willebrand factor research. Von Willebrand factor is the most important adhesion molecule for platelets and it is stored in endothelial cells as we have found very early on, in an organelle called Weibel-Palade bodies. So my work on this paper is actually related to the first observation I ever made scientifically of showing that von Willebrand factor is released from endothelium. Cindy St. H:                         Wow, that's wonderful. And Nicoletta, could you please introduce yourself and tell us a little bit about your background? Nicoletta:                            I'm Italian, I studied in Italy and I did my PhD in the Netherlands, and I've always worked on inflammation and thrombosis during my PhD. One of the major proteins I was working on is ADAMTS13. That is again a protagonist of our paper. Then I moved to Boston, where I had the pleasure to be able to work in Denisa Wagner's lab, and there I continued working on inflammation and ADAMTS13 and now currently I moved here to Bern and I'm bringing my expertise here, but I moved a little bit towards ischemia and reperfusion injury and transplantation. Cindy St. H:                         Interesting. Wow. Denisa, I want to circle back to this factor being one of the first findings that you worked on. How does it feel to still be working on it? Is it still exciting? Dr Wagner:                         It is nice and it's refreshing to come back to it. I did a lot of stuff in between. We did a lot of adhesion molecule work, leukocyte rolling. We made the early knockouts like b-selectin, p-selectin, and von Willebrand factor knockout as well. So it's fun. And by the way, since Nicoletta said that she was Italian, I am originally Czech, from Prague. Cindy St. H:                         Interesting. I did not know that. And actually, Denisa, I don't know if you remember, but when I was a graduate student in Katya Ravid’s lab, we collaborated with you to use some of this intravital imaging on one of our JCI papers. Dr Wagner:                         Oh right, right. I was wondering where I knew your name from. That's funny. Cindy St. H:                         Yes. Yeah, yeah. So it's wonderful to speak to you again. Really I wanted to interview you because I loved this paper, not only because it was a really interesting mechanism that actually I wasn't very well aware of, this citrullination and also because of the beautiful intravital imaging you could do and then link it to patient disease states. Maybe you can start by telling me what's the clinical unmet need or the question that your paper was trying to address? Nicoletta:                            So Denisa Wagner's lab always has worked on neutrophils and NETs and it has been shown that these NETs are involved in thrombosis. So we were curious what happens when even the enzyme that is important to make these NETs, this extracellular DNA, does when it's in the circulation. And this enzyme is of course PAD4 and it is known that it can modify our [inaudible] residues on protein through this process of citrullination. So we went to see if it could modify plasma proteins and as Denisa already said, an important molecule that initiates thrombotic processes is vWF that can be released during inflammation or when there's a damage to the endothelium .  So we went to see what happens if the enzyme that is involved in removing this vWF that is ADAMTS13 happens if it gets modified by this enzyme path. So our question was more like what happens if you have the release of an enzyme that is normally intracellular? What would happen if it gets outside of the cell? Cindy St. H:                         Interesting. So before we get too deep in the weeds, what is citrullinization and why is it important? What do these modifications do? Nicoletta:                            It changes the charge of a protein. It goes and modifies arginine, and it transforms it into citrulline. It changes the charge of a protein and therefore you can imagine if you change a charge of protein it can change even the structure of a protein and if you change the structure then you can change the function. So this is what this modification can do. Cindy St. H:                         And that's what it's doing on the ADAMTS13? It's essentially altering or inhibiting its function? Nicoletta:                            Yes. What we saw is that we can find these citrullinated residues on ADAMTS13 and we identify them by mass spectrometry and then we saw that if it is modified by citrullination, it loses its activity so it doesn't function anymore. Cindy St. H:                         Interesting. Very neat. Could you talk a little bit about the process of where this is happening naturally and where it goes wrong in a diseased state such as either sepsis or aging or just general clotting? Dr Wagner:                         These neutrophil extracellular traps are generated often more during a disease state when there is either an infection or exacerbated inflammation that would be like in sepsis or for example, in a metabolic disorder like diabetes. So there is a lot more of them being generated. Also, for example, in diabetes, PAD4 is elevated inside the neutrophil four-fold. If it's released from diabetic neutrophils , then there would be really a lot more of it. And in aging also, then a NETosis becomes much more prominent. We have done this only with mice, but I believe that it will be also, unfortunately, the case with humans that old mice make a lot more NETs than young mice. Therefore this is relevant to look. Since thrombosis increases both with aging, the incidence of thrombosis, thrombosis increases with a disease like diabetes or in sepsis, you will have micro thrombosis. We thought it would be interesting to study those processes as well, then. Cindy St. H:                         That's really neat. One of the techniques that you utilize heavily in this paper and several of your papers that I'm familiar with is this intravital imaging or intravital microscopy. Just so people can get a sense of what it is you're actually doing, could you maybe describe what that experiment is? Maybe Nicoletta, you could describe that for us? Nicoletta:                            During intravital microscopy, we are able to image in vivo, a vessel in a live mouse. And in this case we use mice and we can label leukocytes and platelets and then look at them in the vessel in vivo and you can then look for a thrombus forming or you can look at the [inaudible 00:23:43] already had leukocyte rolling and you can see what is happening inside the vessel during a proper blood flow and you can damage the vessel in some cases. In our case, in our paper, we do a ferric chloride injury where we damaged the vessel with ferric chloride and therefor you initiate a thrombus development and you can visualize it in vivo and real time. Cindy St. H:                         Excellent. Yes. And hopefully our listeners will look and see the beautiful pictures because those are some serious clots you get forming in the vessels. Yeah. Yeah. And so the other thing that you did was confirming the modification on ADAMTS13, you use mass spectrometry. How difficult was it to confirm that what you thought was happening was happening using that technique? Nicoletta:                            It was very difficult and challenging, I have to say. Dr Wagner:                         See, I would love to hear more about it because you often read, Oh, then we did mass spec and we got this beautiful whatever. Could you tell us a little bit about the struggles? Nicoletta:                            It was quite a struggle. I mean I think trying to identify such a modification that is very, first of all, novel and it changes the math only of one thousandth it's very difficult. To identify you can confuse it with a deiminasion again because of the increase of mass is the same. And another problem was that ADAMTS13, our plasma protein, is low abundance in plasma compared to other plasma proteins like Fibrinogen, that is very, very much abundant. It was a challenge for this reason. So trying to pinpoint out a small, tiny modification already in a protein that is not so abundant in plasma and therefore we have to use this probe, this Biosyn PG program. And we did this in collaboration with Paul Thompson's lab and we were able to then fish out what was modified by the citrullination, but it was very challenging. We tried several different types of techniques that were different types of approaches before being able to show that in vivo. So in human samples we can find this modification. Dr Wagner:                         Nicoletta grew a lot of gray hair during that period. (laughs) Dr Wagner:                         It took us about a year to figure out how we could detect it in vivo because also some antibodies to ADAMTS13 don't work so well. It's a minor protein, but she figured it out. Cindy St. H:                         Wow. That's amazing. Well, congratulations on that. That's excellent. I guess what I'm wondering now is what are the next steps and what might your findings mean in terms of future potential therapeutic options or treatment strategies for different detrimental thrombotic events? Dr Wagner:                         I think what we have really verified that the PAD4 remains active when it circulates in circulation, when the release, and there are several diseases in which PAD4 levels were found to be elevated, like rheumatoid arthritis and what it means in general. That is PAD4 is actually causing havoc. It is citrullinating probably quite indiscriminately. Several proteins may be finding the exposed parts. Maybe it could have some binding sites, but I think it just affects proteins in general and for some of them like, ADAMTS13, this had a very detrimental effect. So in diseases where there is a lot of PAD4, one has to worry about the consequences of citrullinating things and perhaps spot for inhibitors should be used. What do you think, Nicolleta? Nicoletta:                            I totally agree with you. Yes, I totally agree. I mean PAD4 outside the cell could be dangerous, of course. However, we never know if there's something good that it can do that protects by citrullinating proteins so there's so much more to discover about extracellular PAD4 and its effect on the environment. Dr Wagner:                         However, Nicoletta when she wrote a paper at the end she decided to talk about ADAMTS13 as a therapeutic because both she and I, we are convinced that ADAMTS13 it's a possible future therapeutic and it's already given to patients who are lucky in ADAMTS13 and may be given to patients who have thrombotic events in the future, like stroke or myocardial infarction. And these situations are highly pro-inflammatory. Therefore, we would anticipate that in these situations, NETs, and we know NETs are released and therefore, what Nicolleta suggests at the end, is that introducing together with ADAMTS13 an inhibitor of citrullination would be a good thing so that the protein, the ADAMTS13, remains active in circulation. Cindy St. H:                         Wow. So a two-hit strategy. I mean I can think of a handful of potential diseases this would be good for. You know, patients with sickle cell, there's a lot of NETs released then thrombotic events or even stroke. I mean, do you see that this is a potential mechanism that's common to all thrombotic disease or just kind of specific subsets? Nicoletta:                            All is a big word I think, but I think that there are many disorders where together with a thrombotic event, you can find also low levels or low activity of ADAMTS13 and in many of these disorders, nobody knew really why you have a reduction of ADAMTS13 activity, what is happening? Why do you lose this ADAMTS13? What we believe, but of course further studies are needed, is that maybe in these disorders, what is causing the loss of ADAMTS13 is this release of PAD4 because in stroke or in some DIC sepsis, you can find patients or many patients who do have low levels of ADAMTS13 activity and we believe that it's due to maybe citrullination by PAD4. So in that case, I agree with you maybe then that this therapy can be used in different thrombotic events as you suggested. Cindy St. H:                         So what does PAD4 normally do when it's intracellular? What is its, I guess healthy role, in a cell, if it has one? Nicoletta:                            So what is known now is that it really regulates transcription. So that's very important because it citrullinates transcription factors to facilitate transcription. And what Denisa Wagner's lab has identified is that it's extremely important to form these NETs because it citrullinates histone and allows the unraveling of the chromatin and then the NET release. However, it's extremely interesting. We are very interested to understand what else does it do within the cell. Cindy St. H:                         Interesting. That is so neat. I love this story. Dr Sorvillo and Dr Wagner, thank you so much for joining us and congratulations again on a wonderful paper. Dr Wagner:                         Thank you. Nicoletta:                            Thank you for having us and inviting us. Thank you. Cindy St. H:                         So that's it for the highlights from our August issues of Circulation Research. Thank you for listening. This podcast is produced by Rebecca McTavish and edited by Melissa Stoner and supported by the editorial team of Circulation Research. Copy text for the highlighted articles is provided by Ruth Williams. I'm your host, Cindy St Hilaire and this is Discover CircRes, your source for the most up-to-date and exciting discoveries in basic cardiovascular research.  

We discuss masturbation and changing medication for JJ from Olanzapine to Aripiprazole.

#Techno House music

#Techno House music

Executive Editor Michael Roy speaks with Evelyn Attia, M.D., about her research evaluating the benefits of olanzapine compared with placebo for adult outpatients with anorexia nervosa. Be sure to let your colleagues know about the podcast, and please rate and review it on Apple Podcasts, Stitcher, or wherever you listen to it. The podcast is now on Spotify. Listen to other podcasts produced by the American Psychiatric Association. Browse articles online. Also visit the online edition of this month’s Journal to watch a video of Deputy Editor Daniel S. Pine, M.D., present highlights from the issue. Follow the Journal on Twitter. E-mail us at ajp@psych.org

In the first episode of Blood & Cancer, David Henry, MD (http://bit.ly/2MFDfzm), welcomes Richard J. Gralla, MD (http://bit.ly/2ShsxEv), or the Albert Einstein College of Medicine in New York. The topic today centers around antiemetics and ways to use them. And later, Ilana Yurkiewicz, MD (https://stanford.io/2RXPixR), debuts her segment Clinical Correlations all about hematology care. Visit MDedge/hematology-oncology  Show Notes By Emily Bryer, DO Highly emetic chemotherapy regimens include cisplatin, dacarbazine, anthracycline, and cyclophosphamide combinations Treatment should include an NK1 receptor antagonist, dexamethasone, and a 5HT3 antagonist All 5HT3 antagonists should be given only once (no evidence that prn or delayed administration is helpful) Olanzapine is an effective antiemetic, although its precise role and dose are undergoing investigation An all-oral regimen for highly emetic could include Netupitant (NK1) and palonosetron (long-acting 5HT3) (NEPA) + Oral Dex + Olanzapine Moderately emetic chemotherapy regimens include irinotecan and taxotere Treatment should include 5HT3 antagonist and dexamethasone Carboplatin causes more emesis than initially thought Improvement with NK1 antagonist yields a 15% decreased risk of emesis Guidelines now recommending NK1 with carboplatin Low emetic chemotherapy regimens include gemcitabine, pemetrexed as single agent Single drug: one dose of corticosteroid or one dose of 5HT3 antagonist Minimal emetic chemotherapy regimens include vincristine or bleomycin No drugs are recommended for acute or delayed nausea/emesis 20 mg Dexamethasone IV (or 12 mg PO 12 mg) should be administered only on day 1 of chemotherapy. Dexamethasone can be spared after that unless cisplatin (would require 2 days of steroids) Marijuana and THC have some antiemetic properties, but are about one quarter as effective as 5HT3 antagonists Lorazepam may be used in anticipatory emesis started a few days prior to chemotherapy References:  Ann Oncol. 2014 Jul;25(7):1333-9. JCSO 2015;13(4):128-30. JCSO 2016;4(1):11-20. Contact information: Contact us: podcasts@mdedge.com MDedge on Twitter: @mdedgehemonc Dr. Ilana Yurkiewicz on Twitter: @ilanayurkiewicz Dr. Yurkiewicz on MDedge: http://bit.ly/2DItTAb  

Author: Don Stader, MD Educational Pearls: Recent study showed efficacy 5mg IM midazolam > 10mg IM olanzapine > 10mg IM haloperidol for quickly sedating an agitated patient If you have access, ketamine intravenous is the fastest Olanzapine should be used with caution in elderly patients because of its anticholinergic properties Ketamine can transiently worsen psychosis in some mental illness Haloperidol is contraindicated in patients with prolonged QT Olanzapine can be safely given intravenous as another option to your sedating arsenal References: Klein LR, Driver BE, Miner JR, Martel ML, Hessel M, Collins JD, Horton GB, Fagerstrom E, Satpathy R, Cole JB. Intramuscular Midazolam, Olanzapine, Ziprasidone, or Haloperidol for Treating Acute Agitation in the Emergency Department. Ann Emerg Med. 2018 Oct;72(4):374-385. doi: 10.1016/j.annemergmed.2018.04.027. Epub 2018 Jun 7. PubMed PMID: 29885904. Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Kirshner MA, Bies RR, Kapur S, Gharabawi G. A model of anticholinergic activity of atypical antipsychotic medications. Schizophr Res. 2006 Dec;88(1-3):63-72. Epub 2006 Aug 22. PubMed PMID: 16928430. Mankowitz SL, Regenberg P, Kaldan J, Cole JB. Ketamine for Rapid Sedation of Agitated Patients in the Prehospital and Emergency Department Settings: A Systematic Review and Proportional Meta-Analysis. J Emerg Med. 2018 Nov;55(5):670-681. doi: 10.1016/j.jemermed.2018.07.017. Epub 2018 Sep 7. PubMed PMID: 30197153. Summary by Travis Barlock, MS4  | Edited by Erik Verzemnieks, MD    

Welcome back to October's Papers Podcast, this month we move airway from advanced airway management and bring you a broad array of papers. First up we have a look at the relative success of a variety of pharmacological strategies for managing the acutely agitated patient in ED. Next up we have look at the well know CURB-65 score and it's ability to predict the need for critical care interventions. Lastly, we may all feel at times that performing a CT head on those well patients solely because they take anticoagulants may be a little on the excessive side, we review a paper that looks at the yield of positive scans in this cohort. As ever don't just take our word for it, go and have a look at the papers yourself, we would love to hear any comments or feedback you have. Enjoy! Simon & Rob References & Further Reading  IntramuscularMidazolam, Olanzapine, Ziprasidone, or Haloperidolfor TreatingAcuteAgitationin the Emergency Department. Klein LR. Ann Emerg Med. 2018 Performanceof the CURB-65Scorein PredictingCritical CareInterventionsin PatientsAdmitted With Community-AcquiredPneumonia.Ilg A. Ann Emerg Med.2018 Incidenceof intracranial bleedingin anticoagulatedpatientswith minor head injury: a systematic review and meta-analysis of prospective studies. Minhas H. Br J Haematol.2018

Gut and Bronchiolitis; Chemo Nausea and Olanzapine; Developmental Milestones

FDA Drug Safety Podcast: FDA warns about rare but serious skin reactions with mental health drug olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprevv, and Symbyax)

The post Olanzapine (Zyprexa ) appeared first on NURSING.com.

The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = –0.86, p = 0.0001) and olanzapine (Pearson r = –0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t= –0.112, p=0.911).