health care – Page 9 – 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.

Are There Clear and Consistent Racial Differences in Immunity?

So, the short answer is “Probably not.” I did a little digging on this because I heard the recently confirmed HHS Secretary Robert F. Kennedy Jr (RFK Jr) cite studies which he says did indicate there are differences in humoral immunity between Caucasians and African Americans.

Now remember, I’m a retired general hospital psychiatric consultant and my immunology background consists of the standard immunology lecture in medical school. The class I remember most vividly was the one in which the lecturer stopped her lecture abruptly, sighed deeply and looked defeated, probably because she saw the look of confusion on our faces.

Now that you know my credentials, let me just review what I found in a far from exhaustive review of the scientific literature on the topic of whether or not African Americans have, as RFK Jr. remarked, a “better” immune system than Caucasians.

On my own, I found what RFK Jr referred to variously (depending what social media web source you use) as the “Poland” or “pollen” studies as the scientific source of information supporting his view. I suspect it’s this, in which the last author in the citation is GA Poland:

Haralambieva IH, Salk HM, Lambert ND, Ovsyannikova IG, Kennedy RB, Warner ND, Pankratz VS, Poland GA. Associations between race, sex and immune response variations to rubella vaccination in two independent cohorts. Vaccine. 2014 Apr 7;32(17):1946-53. doi: 10.1016/j.vaccine.2014.01.090. Epub 2014 Feb 13. PMID: 24530932; PMCID: PMC3980440.

It was later in the day that I finally also found the NPR news story, the author of which pointed out the same article.

I also found a couple of other articles which tend to contradict the findings of the Poland et al study. One of them was published in eClinicalMedicine in 2023:

Martin CA, Nazareth J, Jarkhi A, Pan D, Das M, Logan N, Scott S, Bryant L, Abeywickrama N, Adeoye O, Ahmed A, Asif A, Bandi S, George N, Gohar M, Gray LJ, Kaszuba R, Mangwani J, Martin M, Moorthy A, Renals V, Teece L, Vail D, Khunti K, Moss P, Tattersall A, Hallis B, Otter AD, Rowe C, Willett BJ, Haldar P, Cooper A, Pareek M. Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis. EClinicalMedicine. 2023 Apr;58:101926. doi: 10.1016/j.eclinm.2023.101926. Epub 2023 Apr 4. PMID: 37034357; PMCID: PMC10071048.

The list of references include the Poland study (reference 27) cited above. The bottom line is the African American immune response to Covid is not “better” than that of white health care workers but the Asian immune response was stronger. I thought it was interesting that in the section “Evidence before this study,” the authors point out that in one previous study, African Americans had lower antibody responses to vaccination than Whites.

I looked at only one other study, published in Clinical Microbiology Review in 2019;

Zimmermann P, Curtis N2019.Factors That Influence the Immune Response to Vaccination. Clin Microbiol Rev 32:10.1128/cmr.00084-18.https://doi.org/10.1128/cmr.00084-18

OK, so I didn’t hunt through all 582 references, but I thought it was enough to note that the authors didn’t mention race as even being relevant anywhere in the body of the paper.

That said, I suspect the more important fact to focus on is racial disparity regarding African Americans even getting vaccines, especially the Covid vaccine. Vaccine hesitancy is common in this population and probably more important to address rather than whether or not there are significant racial differences in immunogenicity. The major challenge is providing accurate information about vaccines in general and Covid vaccines in particular.

The CDC Advisory Committee includes African American members who attend each meeting and emphasize the importance of including black people in vaccination campaigns. OK, so why was the meeting this month cancelled, postponed, or whatever?

Hey, I’m just an old psychiatrist, so don’t take my word for it about anything here. Ask an immunologist. If the immunologist gives you a blank look, you could try a Ouija Board.

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.”

86: Cancer Rates in Iowa – Rounding@IOWA

Iowa's cancer rates are among the highest in the country, and they are rising. In this episode of Rounding@Iowa, Dr. Gerry Clancy and guest experts Dr. Mary Charlton and Dr. Mark Burkard discuss the data, risk factors, and prevention strategies clinicians can use to make a difference. CME Credit Available: https://uiowa.cloud-cme.com/course/courseoverview?P=0&EID=81274 Host: Gerard Clancy, MD Senior Associate Dean for External Affairs Professor of Psychiatry and Emergency Medicine University of Iowa Carver College of Medicine Guests: Mark E. Burkard, MD, PhD Professor of Internal Medicine-Hematology, Oncology, and Blood and Marrow Transplantation University of Iowa Carver College of Medicine Director, University of Iowa Health Care Holden Comprehensive Cancer Center Mary Charlton, PhD Professor of Epidemiology Director, Iowa Cancer Registry Iowa College of Public Health Financial Disclosures: Dr. Clancy, Dr. Burkard, Dr. Charlton, 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 0.75 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 0.75 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. UAN: JA0000310-0000-25-090-H99 Physician: The University of Iowa Roy J. and Lucille A. Carver College of Medicine designates this enduring material for a maximum of 0.75 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.) References/Resources: Iowa Cancer Plan

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.

Artificial Intelligence in Managing Messages from Patients

I ran across another interesting article in the JAMA Network about Artificial Intelligence (AI) with respect to health care organization managing messages from patients to doctors and nurse. The shorthand for this in the article is “in-basket burden.” Health care workers respond to a large number of patients’ questions and it can lead to burnout. Some organizations are trying to test AI by letting it make draft replies to patients. The results of the quality improvement study were published in a paper:

English E, Laughlin J, Sippel J, DeCamp M, Lin C. Utility of Artificial Intelligence–Generative Draft Replies to Patient Messages. JAMA Netw Open. 2024;7(10):e2438573. doi:10.1001/jamanetworkopen.2024.38573

One of the fascinating things about this is the trouble we have naming the problems with misinformation that AI has. We tend to use a couple of terms interchangeably: hallucinations and confabulation. Whatever you call it, the problem interferes with communication between health care workers and patients.

Dr. English describes the interference as a “whack-a-mole” issue, meaning every time they think they got the hallucination/confabulation problem licked, the AI comes up with another case of miscommunication.

Just for fun, I did a web search trying to find out whether “hallucination” or “confabulation” fit the AI behavior best. Computer experts tend to use the term “hallucination” and neuropsychologists seem to prefer “confabulation.” I think this community chat site gives a pretty even-handed discussion of the distinction. I prefer the term “confabulation.”

Anyway, there are other substantive issues with how using AI drafts for patient messaging affects communication. I think it’s interesting that patients tend to think AI is more empathetic than medical practitioners. As Dr. English puts it: “This GPT is nicer than most of us,” and “And ChatGPT, or any LLM, isn’t busy. It doesn’t get bored. It doesn’t get tired.” The way that’s worded made me think of a scene from a movie:

OK, so I’m kidding—a little. I think it’s important to move carefully down the path of idealizing AI. I think back to the recent news article about humans teaching AI how to lie and scheme. I remember that I searched the web with the question “Can AI lie?” and getting a reply from Gemini because I have no choice on whether or not it gives me its two cents. I’m paraphrasing but it said essentially, “Yes, AI can lie and we’re getting better with practice.”

I like Dr. English’s last statement, in which she warns us that AI can be a fun tool which clinicians need to have a healthy skepticism about. It may say things you might be tempted to gloss over or even ignore, like:

“I’ll be back.”

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.