Psychiatry – Page 6 – Go Retire Psychiatrist

FDA Announces Clozapine REMS Program Eliminated

As of February 24, 2025, the FDA has eliminated the Clozapine Risk Evaluation and Mitigation Strategy (REMS) program. See the FDA link for details. Below is the announcement.

“Latest Update

February 24, 2025 – Beginning today, FDA does not expect prescribers, pharmacies, and patients to participate in the risk evaluation and mitigation strategies (REMS) program for clozapine or to report results of absolute neutrophil count (ANC) blood tests before pharmacies dispense clozapine. FDA still recommends that prescribers monitor patients’ ANC according to the monitoring frequencies described in the prescribing information. Information about severe neutropenia will remain in the prescribing information for all clozapine medicines, including in the existing Boxed Warnings.

Although the risk of severe neutropenia with clozapine still exists, FDA has determined that the REMS program for clozapine is no longer necessary to ensure the benefits of the medicine outweigh that risk. Eliminating the REMS is expected to decrease the burden on the health care delivery system and improve access to clozapine. FDA has notified the manufacturers that the clozapine REMS must be eliminated. FDA has instructed the clozapine manufacturers to formally submit a modification to eliminate the Clozapine REMS and to update the prescribing information, including removing mandatory reporting of ANC blood tests to the REMS program.

In the coming months, FDA will work with the clozapine manufacturers to update the prescribing information and eliminate the Clozapine REMS.”–FDA

Addiction Not the Same as Neuroadaptation

It’s common to read or hear people say they’re “addicted” to all sorts of things, like chocolate, but there’s a difference between addiction and adaptation. Adaptation can also be called “dependence” or the fancier “neuroadaptation.”

This can foster a discussion about whether you can be addicted to antidepressants, which by extension, could mean it’s difficult to discontinue them. Presumably, that would point to withdrawal symptoms being the obstacle to “getting off” them. Comparing them in terms of which one is more difficult to quit (as noted in the news lately) is fraught with difficulty.

Because I’m a retired psychiatrist, I searched the medical literature to refresh my knowledge about the issue. It turns out, according to a recent review, that it’s important to distinguish between dependence (neuroadaptation) and addiction.

The thing about addiction is that it’s about misusing or abusing substances in a compulsive way despite adverse consequences. Medical students used to remember it (for exams) as the 4 C’s: compulsion, craving, control (the loss of), and consequences (negative). I remember one doctor who added another c: conniving (to obtain substances).

On the other hand, dependence is marked by the adaptation of brain receptors to a substance and which doesn’t involve any of the c’s. This is the way to differentiate addiction from dependence, the latter being a consequence of taking antidepressants. One recent review article does a pretty good job of explaining this:

“Physical dependence to antidepressants may occur in some patients, caused by adaptation of the brain to long-term use of the medication. As pharmacologically defined, this physical dependence is a distinct phenomenon from addiction, and is manifested by a drug withdrawal syndrome.” — Horowitz MA, Framer A, Hengartner MP, Sørensen A, Taylor D. Estimating Risk of Antidepressant Withdrawal from a Review of Published Data. CNS Drugs. 2023 Feb;37(2):143-157. doi: 10.1007/s40263-022-00960-y. Epub 2022 Dec 14. PMID: 36513909; PMCID: PMC9911477.

The authors make the point that pretty much all antidepressants can cause dependence if you take them long enough. But with the possible exception of tranylcypromine (Parnate), they don’t lead to abuse or addiction. That was an interesting reminder. Parnate has a chemical structure similar to amphetamine and there are old case reports describing patients who usually have other substance use disorders abusing Parnate.

Anyway, antidepressants can lead to dependence which can be detected only if they stop using them. Withdrawal can be extremely uncomfortable and can last weeks to months, uncommonly for years.

Withdrawal syndromes vary among different substances. Alcohol and heroin can cause severe withdrawal that has to be managed in a hospital. That’s not to say it’s impossible to suffer antidepressant withdrawal serious enough to warrant hospitalization, but it would be rare. Partly that’s due to the difference in neuroreceptors.

Serotonergic receptors, for example, can be occupied by serotonergic antidepressants and lead to dependence mediated by neuroadaptation. If the antidepressant is abruptly stopped, there will be withdrawal, partly depending on the chemical half-life of the drug. Withdrawal can be marked by headache, dizziness, falls, electric shock sensations, and suicide attempts, for example.

Opioid and benzodiazepine withdrawal are mediated by opioid and Gamma Amino Butyric Acid (GABA) receptors respectively. Withdrawal symptoms can include but are not limited to tremor, sweating, seizures and delirium for benzodiazepine withdrawal, and muscle jerks, sweating, bone pain, nausea and vomiting, diarrhea, and muscle spasms for opioids such as heroin. Both may require medical detoxification in a hospital.

Who’s to say which withdrawal syndrome is worse? They’re both bad.

There’s not a lot of scientific literature out there on antidepressant withdrawal. The authors of the article cited above ended up with only 11 papers over a 20-odd year span after their search.

On average, antidepressants with shorter half-lives tend to be associated with withdrawal. Table 5 in the article cited above identifies the ones with lower to higher risk. Table 6 is a preliminary effort to categorize the level of risk to develop antidepressant withdrawal for an individual patient.

Rounding@Iowa Podcast: “Challenges in Transitioning Seriously Ill Patients from Pediatric to Adult Systems of Care”

I listened to the Rounding@Iowa podcast of February 11, 2025, “Challenges in Transitioning Seriously Ill Patients from Pediatric to Adult Systems of Care.”

89: Tick-borne Illnesses – Rounding@IOWA

Join Dr. Clancy, Dr. Appenheimer & Dr. Barker as they discuss prevention, diagnosis and treatment of various tick-borne illnesses. CME Credit Available: https://uiowa.cloud-cme.com/course/courseoverview?eid=82296 Host: Gerard Clancy, MD Senior Associate Dean for External Affairs Professor of Psychiatry and Emergency Medicine University of Iowa Carver College of Medicine Guests: Ben Appenheimer, MD Clinical Associate Professor of Internal Medicine-Infectious Diseases Assistant Director, Infectious Diseases Fellowship Program Associate Clinical Director, Infectious Diseases Co-Medical Director, TelePrEP, University of Iowa Health Care University of Iowa Carver College of Medicine Jason Barker, MD Associate Professor of Internal Medicine-Infectious Diseases University of Iowa Carver College of Medicine Financial Disclosures: Dr. Gerard Clancy, his guests, and Rounding@IOWA planning committee members have disclosed no relevant financial relationships. Nurse: The University of Iowa Roy J. and Lucille A. Carver College of Medicine designates this activity for a maximum of 1.0 ANCC contact hour. Pharmacist and Pharmacy Tech: The University of Iowa Roy J. and Lucille A. Carver College of Medicine designates this knowledge-based activity for a maximum of 1.0 ACPE contact hours. Credit will be uploaded to the NABP CPE Monitor within 60 days after the activity completion. Pharmacists must provide their NABP ID and DOB (MMDD) to receive credit. JA0000310-0000-26-038-H01 Physician: The University of Iowa Roy J. and Lucille A. Carver College of Medicine designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other Health Care Providers: A certificate of completion will be available after successful completion of the course. (It is the responsibility of licensees to determine if this continuing education activity meets the requirements of their professional licensure board.)

This was a very interesting presentation about the challenges of helping persons with life-limiting conditions (for example, hemophilia, cystic fibrosis, sickle cell anemia and more) transition from pediatric to adult systems of care. Most of the discussion was about the difficulty in finding doctors who would be willing and able to assume care of patients who had survived to adulthood who had been previously seen in pediatrics throughout childhood.

I listened very carefully to the whole podcast, waiting to hear about what the role of mental health care professionals would be in this kind of transition. There was no mention of it, not even after one of the presenters described a patient who was starting to have hallucinations.

My role as a consulting psychiatrist in a general hospital was mainly to see those with chronic diseases who were being treated by colleagues during a bout of cystic fibrosis or sickle cell crisis. I remember they were young adults, struggling with emotional distress and disruptive behavior.

I was surprised at the lack of discussion about the role of mental health assessments, diagnoses, and treatment including psychotherapy during transitions from pediatric to adult health care. Not that I would have had much to offer other than questions about how mental health professionals could be helpful regarding transitions—but I think they would have not been out of place.

I took a quick look at the resources provided. One of them was a University of Iowa website, the Iowa Center for Disabilities and Development: Transition to Adulthood Clinic For Teens and Young Adult Ages 14-30. Even here, the role of a psychologist was to evaluate learning problems.

One of the discussants mentioned a program called Got Transition, which has a very comprehensive website. There was a section for Special Populations and a list of resources and research when I searched the site using the term “mental health.” It was hard to find a section specific to the population under discussion in the podcast. On the other hand, it was very comprehensive.

In this podcast, discussants talked about the importance of a team approach to transitions. I wonder if there’s a place on the team for psychiatry.

Rife vs Ripe: Which is Right?

I noticed a couple of things about one of the President’s many new Executive Orders, which was “ESTABLISHING THE PRESIDENT’S MAKE AMERICA HEALTHY AGAIN COMMISSION,” or MAHA for short. It was posted on February 13, 2025. One thing it reminded me of is the tax filing season, which is upon us (everything reminds me of the tax filing season around this time of year). The other thing was a short article about the IRS, which is cutting staff sharply in response, probably as a response to the federal government workforce layoffs generally. One sentence in the article read:

“The IRS layoffs, first reported by the New York Times, come as part of a broader effort by President Donald Trump and Elon Musk’s overhaul of the federal government, which they argue is too bloated and inefficient, and ripe with waste and fraud.”

I put the word “ripe” in bold-face type because I sensed that the writer probably meant “rife” instead. I looked up the definitions of both just to make sure: Rife means abundant and ripe means mature (possibly overly mature as in smelly and ready for the garbage can).

I wonder if “rife” or “ripe” could apply to MAHA. I’m all for making us healthy. I agree with promoting health. I’m not sure what is meant by “assess the prevalence of and threat posed by the prescription of selective serotonin reuptake inhibitors, antipsychotics, mood stabilizers, stimulants, and weight-loss drugs.” It sounds like a shot across the bow for psychiatrists and primary care physicians.

Some of the content may be either “rife” (or is it “ripe”?) with potentially misleading innuendo, implying that health care professionals are not doing all we can already to promote health. I agree with promoting research into the “root causes” for mental illness. However, some people need psychiatric medications for “just managing disease.” Reducing the suffering of those who are tortured by depression and delusions and hallucinations makes sense because that’s the humane thing to do.

This reminds me of a very interesting article about what some scientists think about how life began on this planet and how it might start elsewhere in the universe. Some think life evolves mainly by chance, by a cosmic accident. Others think it’s inevitable and occurs when planetary conditions are right. So that might mean there’s a good chance there are extraterrestrials are out there. If they are, what would they think of us?

And this reminds me of a quote from the movie, Men in Black. Agent K is showing Edwards a universal translator, one of the many wonders in the extraterrestrial technology room, which gives us a perspective on how humans rank in the universe:

Agent K: We’re not even supposed to have it. I’ll tell you why. Human thought is so primitive it’s looked upon as an infectious disease in some of the better galaxies.

So is the universe “rife” with life—or is it “ripe”?

FDA Has Yet to Decide on What to Do About the Clozapine REMS Program

I checked on what the FDA is doing about changing or closing down the Clozapine REMS program. It doesn’t look like they’ve taken any action yet. Recall there was a Clozapine REMS Advisory Committee meeting about this on November 19, 2024 that I posted about recently. The upshot was that the committee voted overwhelmingly (14 yes to 1 No) to get rid of the Clozapine REMS program.

What I didn’t realize until today was that a former colleague of mine was a member of the committee. Dr. Jess Fiedorowicz, MD, PhD was on staff at The University of Iowa Health Care in the past and is now head of the Dept of Mental Health at The Ottawa Hospital in Ottawa, Ontario in Canada. I’ve included the YouTube video below of the meeting and you can find Dr. Fiedorowicz’s remarks via Zoom video at around the 8:05 or so mark into the meeting. You can view his vote to shut down the REMS program at around 8:33.

I also found out about a group called The Angry Moms (those who care for family members on clozapine) who are focused on stopping the Clozapine REMS program and one of their web pages makes it pretty clear they’re not happy that the FDA has not made a decision about REMS yet.

They mention Dr. Gil Honigfeld, PhD who I’d never heard of until now. You can tell from his T-shirt how he feels about clozapine. He has been called the “Godfather of Clozapine” and his opinion about the REMS program along with a short history of clozapine can be found at this link.

I don’t know what the FDA will do about the Advisory Committee’s recommendation, but I hope they do it soon.

How About Artificial Intelligence for Helping Reduce Delirium in the ICU?

I got the Winter 2025 Hopkins Brain Wise newsletter today and there was a fascinating article, “Using AI to Reduce Delirium in the ICU: Pilot Study will explore AI headset can help reduce delirium and delay post-delirium cognitive decline.”

The article has exciting news about what researchers are doing which will, hopefully, reduce the incidence of delirium in the intensive care unit (ICU). Another Hopkins researcher has published a study that has already used AI algorithms to detect early warning signs of delirium in the ICU;

Gong, Kirby D. M.S.E.1; Lu, Ryan B.S., M.D., Ph.D.2; Bergamaschi, Teya S. M.S.E., Ph.D.3; Sanyal, Akaash M.S.E.4; Guo, Joanna B.S.5; Kim, Han B. M.S.E.6; Nguyen, Hieu T. B.S., Ph.D.7; Greenstein, Joseph L. Ph.D.8; Winslow, Raimond L. Ph.D.9; Stevens, Robert D. M.D.10. Predicting Intensive Care Delirium with Machine Learning: Model Development and External Validation. Anesthesiology 138(3):p 299-311, March 2023. | DOI: 10.1097/ALN.0000000000004478

The list of references for the study of course include those by Dr. E. Wesley Ely, who delivered an internal medicine grand rounds about delirium at the University of Iowa in 2019.

Anybody who reads my blog knows I’ve been knocking AI for a while now. However, anybody who also knows that I’m a retired consultation-liaison psychiatrist knows how interested I am in preventing delirium in the hospital. I worked as a clinical track professor for many years at The University of Iowa Health Care in Iowa City.

It’s fortuitous that I found out about what Johns Hopkins research is doing on this topic because the director of the Johns Hopkins psychiatry department happens to be Dr. Jimmy Potash MD, MPH, who’s identified on the newsletter. He was the head of the psychiatry department at the University of Iowa from 2011-2017.

Besides all the name-dropping I’m doing here, I’m also admitting that I’ll probably soften my position against AI if the research described here does what the investigators and I hope for, which is to reduce delirium in the ICU.

All Jokes Aside, What Do I think About the Book “Caste: The Origins of Our Discontents?”

I just finished reading Isabel Wilkerson’s book, “Caste: The Origins of Our Discontents.” It was a painful read because it talks about racism in America, which is a part of my lived experience. Wilkerson’s compares it to the Nazi persecution of the Jews and the caste organization in India. The chapter on the pillars of caste make sense to me.

When I reached the last section (not at all “final” by any means), which is called “Awakening,” I was not surprised that there were no prescriptions or outlines or action plans for how to eliminate caste in any culture. It turns out that we’re all responsible for becoming aware of how we all are complicit in some way with maintaining caste divisions in society. And the word Wilkerson used for how to begin is “empathy,” or somehow becoming conscious of that tendency and to replace it with understanding.

As Wilkerson emphasizes, empathy isn’t sympathy or pity. Empathy is walking a mile in someone else’s shoes, as the song goes. But she goes a step further and uses the term “radical empathy.” It’s difficult to define concretely. It goes beyond trying to imagine how another person feels, going the extra mile and learning about what the other person’s experience. It’s not about my perspective; it’s about yours. It’s not clear exactly how to make that deep connection. She uses terms like “spirit” which may or may not resonate with a reader searching for a recipe or a cure.

Politics turns up in the book. How could it not? I’m going to just admit that I wanted to make this post humorous somehow, especially after I saw Dr. H. Steven Moffic’s article in Psychiatric Times about whether psychiatrists are to act in the role of “bystanders” or “upstanders” in the present era of political and social turmoil. He specifically mentioned the Goldwater Rule, which is the American Psychiatric Association Ethics Annotation barring psychiatrists from making public statements of a diagnostic opinion about any individual (often a politician) absent a formal examination or authorization to make any statements. The allusion to a specific person is unmistakable.

But, as a retired psychiatrist, I’m aware that my sense of humor could be deployed as a defense mechanism and it would certainly backfire in today’s highly charged political context. I’m not sure whether I’m a bystander or an upstander.

Sena and I had a spirited debate about whether America has a caste system or not. I think it’s self-evident and is nothing new to me. I suspect that calling racism (which certainly exists in the United States) a form of casteism would not be altogether wrong. Wilkerson mentions a psychiatrist, Sushrut Jadhav, who is mentioned in the Acknowledgments section of her book. Jadhav is a survivor of the caste system in India. I found some of insights on caste and racism in web article, “Caste, culture and clinic” which is the text of an interview with him.

His answers to two questions were interesting. On the question of whether there is a difference between the experience of racism and caste humiliation, he said “None on the surface” but added that more research was needed to answer the question adequately. And to the question of whether it’s possible to forget caste, he said you have to truly remember it before you can forget it—and it’s important to consider who might be asking you to forget it.

This reminded me of the speech in the movie “Guess Who’s Coming to Dinner,” said by John Prentice (played by Sidney Poitier) to his father:

“You’ve said what you had to say. You listen to me. You say you don’t want to tell me how to live my life? So, what do you think you’ve been doing? You tell me what rights I’ve got or haven’t got, and what I owe to you for what you’ve done for me. Let me tell you something. I owe you nothing! If you carried that bag a million miles, you did what you were supposed to do because you brought me into this world, and from that day you owed me everything you could ever do for me, like I will owe my son if I ever have another. But you don’t own me! You can’t tell me when or where I’m out of line, or try to get me to live my life according to your rules. You don’t even know what I am, Dad. You don’t know who I am. You don’t know how I feel, what I think. And if I tried to explain it the rest of your life, you will never understand. You are 30 years older than I am. You and your whole lousy generation believes the way it was for you is the way it’s got to be. And not until your whole generation has lain down and died will the deadweight of you be off our backs! You understand? You’ve got to get off my back! Dad. Dad. You’re my father. I’m your son. I love you. I always have and I always will. But you think of yourself as a colored man. I think of myself as a man. Hmm? Now, I’ve got a decision to make, hmm? And I’ve got to make it alone. And I gotta make it in a hurry. So, would you go out there and see after my mother?”

And there was this dialogue that Sena found on the web, which was similar to that of John Prentice. It was a YouTube fragment of a 60 minutes interview in 2005 between actor Morgan Freeman and Mike Wallace. Wallace asked Freeman what he thought about Black History Month. Freeman’s answer stunned a lot of people because he said he didn’t want Black History Month and said black history is American history. He said the way to get rid of racism was to simply stop talking about it. His replies to questions about racism implied he thought everyone should be color blind. John Prentice’s remarks to his father are in the same vein.

I grew up thinking of myself as a black person. I don’t think there was any part of my world that encouraged me to think I was anything different. I think Wilkerson’s book is saying that society can’t be colorblind, but that people can try to walk a mile in each other’s shoes.

Is Edinburgh Manor in Iowa Haunted?

I have no idea whether an old former county home in Jones County is one of the most haunted places in the Midwest or Iowa or the USA. And I wouldn’t be saying that if Sena and I had not watched a TV show called “Mysteries of the Abandoned” (broadcast on the Science Channel) which aired a 20-minute segment about Edinburgh Manor the other night.

Supposedly, Edinburgh Manor started off as a county poor farm back in the 1800s, which didn’t do well and then quickly declined into an asylum for the mentally ill. When a couple bought the old place after it closed sometime between 2010 and 2012, they started to report having paranormal experiences and it was then off to the races for the place to become a haunted attraction, for which you can buy tickets for day passes and overnight stays.

There’s a 10-minute video by a newspaper reporter who interviews the wife and which shows many video shots of the house. I can’t see any evidence that it’s on the National Register of Historic Places.

What this made me think of was the Johnson County Historic Poor Farm here in Iowa City, which is on the National Register of Historic Places. We’ve never visited the site, but you don’t pay admission and the tone and content of the information I found on the website is nothing like what’s all over the web about Edinburgh Manor. There are no ghosts tickling anybody at the Johnson County Historic Poor Farm.

There’s a lot of education out there about the history of county poor farms in general. In Johnson County, Chatham Oaks is a facility that houses patients with chronic mental illness and it used to be affiliated with the county home. It’s now privatized. The University of Iowa department of psychiatry used to round on the patients and that used to be part of the residents training program (including mine).

I found an hour-long video on the Iowa Culture YouTube site about the history of Iowa’s county poor farms. It was very enlightening. The presenter mentioned a few poor farms including the Johnson County site—but didn’t say anything about Edinburgh Manor.

Music Therapy in End of Life Care Podcast: Rounding@Iowa

I just wanted to make a quick shout-out to Dr. Gerry Clancy, MD and Music Therapist Katey Kooi about the great Rounding@Iowa podcast today. The discussion ran the gamut from how to employ music to help patients who suffer from acute pain, agitation due to delirium and dementia, all the way up to even a possible role for Artificial Intelligence in the hospital and hospice.

89: Tick-borne Illnesses – Rounding@IOWA

Could Artificial Intelligence Help Clinicians Conduct Suicide Risk Assessments?

I found an article in JAMA Network (Medical News & Perspectives) the other day which discussed a recent study on the use of Artificial Intelligence (AI) in suicide risk assessment (Hswen Y, Abbasi J. How AI Could Help Clinicians Identify American Indian Patients at Risk for Suicide. JAMA. Published online January 10, 2025. doi:10.1001/jama.2024.24063).

I’ve published several posts expressing my objections to AI in medicine. On the other hand, I did a lot of suicide risk assessments during my career as a psychiatric consultant in the general hospital. I appreciated the comments made by one of the co-authors, Emily E. Haroz, PhD (see link above).

Dr. Haroz preferred the term “risk assessment” rather than “prediction” referring to the study (Haroz EE, Rebman P, Goklish N, et al. Performance of Machine Learning Suicide Risk Models in an American Indian Population. JAMA Netw Open. 2024;7(10):e2439269. doi:10.1001/jamanetworkopen.2024.39269).

The model used for the AI input used data available to clinicians in patient charts. The charts can be very large and it makes sense to apply computers to search them for the variables that can be linked to suicide risk. What impressed me most was the admission that AI alone can’t solve the problem of suicide risk assessment. Clinicians, administrators, and community case managers all have to be involved.

The answer to the question “How do you know when someone’s at high risk?” was that the patient was crying. Dr. Haroz points out that AI probably can’t detect that.

That reminded me of Dr. Igor Galynker, who has published a lot about how to assess for high risk of suicide. His work on the suicide crisis syndrome is well known and you can check out his website at the Icahn School of Medicine at Mount Sinai. I still remember my first “encounter” with him, which you can read about here.

His checklist for the suicide crisis syndrome is available on his website and he’s published a book about as well, “The Suicidal Crisis: Clinical Guide to the Assessment of Imminent Suicide Risk 2nd Edition”. There is also a free access article about it on the World Psychiatry journal website.

Although I have reservations about the involvement of AI in medicine, I have to admit that computers can do some things better than humans. There may be a role for AI in suicide risk assessment, and I wonder if Dr. Galynker’s work could be part of the process used to teach AI about it.