John J. Miller, MD

Imagine practicing medicine in the early 1900s before the advent of antibiotics, anesthesia, laboratory data, radiology, and intensive care units. Clinicians did not need to know as much as we do today. Of course, that also meant there was less we could do for our patients. I can recall as a child during the 1960s my grandmother was hospitalized for a week for a headache—and the prescribed treatment was to rest.

Fortunately, we continue to expand our understanding in all medical specialties at an exponential rate. Add to that the extraordinary demands of clinical practice, and at the end of our workday, we simply do not have the energy to read an

in a medical journal. Not surprisingly, this void has been filled by 

, where the goal is to focus on learning all that is new and important in our chosen field of medicine. These conferences are often enriched by reunions with our longtime friends and colleagues as well as by spending a few extra days vacationing away from our usual routines. This combination of events likely enhances retention of the material learned and provides a well-needed respite from our daily medical practices.

John J. Miller, MD, is medical director, Brain Health, Exeter, New Hampshire; Editor in Chief, 

; staff psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Exeter Hospital, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

In the attempt to keep mental health professionals up-to-date, the mission of 

 since 1985 has been to provide evidence-based, peer-reviewed, clinically relevant information for psychiatric clinicians in an engaging format. We appreciate your feedback that Psychiatric Times

 is your go-to source for timely, diverse, and digestible monthly publication. Similarly, over the past several years, the 

 website has blossomed into a highly regarded resource with daily updates and a large archive to explore.

The information trifecta has been completed with our annual CME conference, which is modeled after our well-respected monthly publication. Through numerous brief lectures—most 15 to 30 minutes long—presented by leading topic experts, the conference provides a rich, diverse curriculum that is designed to reward attendees with a meaningful and broad educational experience. Plus, the CME credits earned are a pleasant value-added perk.

will be held September 30 through October 2. Building on last year’s successful virtual conference, we are excited to offer a hybrid conference model that allows attendees to participate in person—in 

—or virtually, with both formats providing access to the same great information and same outstanding faculty. In addition to updates on the usual topics like 

, presenters will share their experiences and insights on numerous specialty topics.

This year’s conference will begin with a mini-symposium on “Psychiatry in the Age of 

,” exploring how our lives changed during this once-in-a-century pandemic, and how this experience has changed the way we practice psychiatry, grieve from a global disaster, and heal from the physical and mental scars left behind.

Needless to say, the past 18 months have been extraordinary in many ways: The United States and our world community came to a screeching halt as the 

 pandemic ramped up. So many aspects of life that we took for granted were off-limits, and we had to reimagine how to move forward safely. For instance, before the pandemic, I had never engaged in 

. Yet, like so many of you, starting in mid-March 2020, I began meeting with all of my patients either through doxy.me or over a telephone line.

I never fully adjusted to this new way of practicing psychiatry, and beginning a few months ago, I started seeing patients again in my small but comfortable office. It has been fascinating to hear the many different opinions about telemedicine. One thing seems clear: A hybrid model will likely become the “new normal” in health care delivery.

Many other lessons have been learned—like the importance of 

and caregivers—and hopes for improvement abound as we venture forth. As many have said, returning to normal should not be the goal: We should aim to better incorporate the successful innovations gleaned from the pandemic into our routines.

In addition, the COVID-19 pandemic remains unleashed in many countries, and although vaccination rates in the United States continue to rise, most of us still feel off-balance because of the raw experiences of the past 18 months. There is much to feel, discuss, share, and process about this viral pandemic, and this symposium’s sessions will explore all of that, as well as the psychiatric implications of COVID-19.

In another vein, the conference will feature a series of presentations examining what we know about 

, tetrahydrocannabinol, and cannabidiol, a timely focus with cannabis legalized—both medically and recreationally—in a rapidly growing number of states. In the not-so-distant future, it could be legalized throughout the United States. Similarly, psychedelics, which had been marginalized since the 1960s, have resurfaced with possible benefits for some psychiatric disorders. For instance, more than 50 clinical trials are currently registered with the US Food and Drug Administration researching the putative benefits of psilocybin for various indications. How might psychedelics become a novel psychiatric treatment in our toolbox? The conference will explore new research and what you need to know.

So many more equally fascinating talks are scheduled. In partnership with 

 (PER®), we are continuing our conference model of presenting many diverse topics in briefer time intervals to allow for a broad curriculum, providing you with key take-home points in a clear and focused manner. I invite you to review our 

 to attend either in person or virtually.

My favorite part of our annual conference is the ample time for faculty interaction with attendees to discuss cases or delve deeper into topics of interest. For participants attending in person, please join us for a networking reception on the evening of Friday, October 1. If you have previously visited San Diego, you already know why it is such a special city. If you haven’t, it is time to find out.

I look forward to seeing you there—and learning together! ❒

Articles

Recognizing the need to stay up-to-date with psychopharmacology and issues affecting psychiatric practice, Psychiatric Times' Editor in Chief invites readers to join him and leaders in psychiatry for a fascinating educational conference.

Perfecting the Trifecta

, a research team at Icahn School of Medicine at Mount Sinai Health System in New York City made a fascinating discovery: Early life stress in mice resulted in an epigenetic modification of methyl groups on histone-3 in neurons in the nucleus accumbens, which in turn led to a lifelong increase in the mice’s vulnerability to stress. The team then demonstrated that treating the mice during exposure to early life stress with pinometostat, a drug currently in clinical trials to treat acute myeloid leukemia in humans, inhibited the enzyme responsible for this epigenetic methylation modification and decreased the effect of early-life stress exposure on 

This study is but one of a growing number of publications demonstrating the essential role of epigenetics in animal development, health, and disease. Without much fanfare, our understanding of epigenetics has been a significant paradigm shifter. Before we explore epigenetics, we need to review the foundational field of genetics.

The 3 billion base pairs that constitute the human genome is the sequence of covalently bonded nucleic acids—adenine (A), thymine (T), cytosine (C), and guanine (G)—that form the double helix of DNA. This sequence forms the basis of the field of genetics and is created when the sperm joins the egg to form a zygote, which will contain this unique DNA sequence that remains constant throughout our life. In the case of identical twins, 100% of this DNA sequence is exactly the same, as both twins derive from the same zygote. With fraternal twins, 2 different sperm fertilize 2 different eggs to create 2 unique zygotes that have DNA sequences as different as 2 siblings with the same parents.

Let’s look at the genetic risk of schizophrenia, for example. In the general population, the risk of developing schizophrenia is about 1%, but if your identical twin develops schizophrenia, your risk increases to 50% due to the identical shared genome. In fraternal twins, the risk drops to roughly 16%, and in siblings it further drops to 9%. This demonstrates the role genetics plays on increasing or decreasing a person’s risk for various medical conditions. Significantly, the identical twin also has a 50% likelihood of not developing schizophrenia, which is attributed to numerous nongenetic factors. One of these factors is the individual’s epigenome, which can be different than 

In 2001, the Human Genome Project (an international consortium of research labs spearheaded by the US National Institutes of Health) and Celera Genomics (a private research company) announced they had independently completed a first draft of the sequencing of the human genome’s 3 billion base pairs. By 2003, the final draft was complete. Speculation by scientists, world leaders, and the media projected that, over the next decade, science and medicine would discover the genetic basis to many human diseases and disorders, with associated novel treatments. The complete sequencing of the human genome was an incredible achievement that continues to advance our understanding of the role of genes on health and disease. However, 20 years later it is disappointing to see how few actionable treatments have been developed. So, what’s next?

The foundation of the epigenome involves covalent changes on certain areas of our chromosomes that will either increase or decrease the amount of activity at genes, hence impacting which gene products will be made in each particular cell. Think of the epigenetic processes like the software that determines which programs on a computer’s hard drive (the DNA genome) will be opened in RAM (in our analogy the genes that are ultimately expressed, creating our phenotype). The zygote has access to 100% of the genome. As embryological development occurs, cells begin to specialize and only require a small subset of the 20,000 or so protein coding genes that are available. One line of cells will begin to only produce proteins necessary for skin, while another set of cells will produce proteins for muscle, and yet another for neurons. This is an energy efficient process.

 that the chromosomal DNA/histone complex can be covalently modified to decrease or increase gene expression: methylation of the gene, or adding chemical tags to histones (the proteins around which the DNA is wrapped).

 In humans, the part of the gene that is methylated is the “promoter sequence,” a specific sequence of nucleotides, including a large density of CpG sites, which serve as a beacon and landing pad for the proteins that will then transcribe the messenger RNA (mRNA). mRNA will ultimately code for the gene’s protein. The more methyl groups attached to the promoter sequence, the less gene product will be synthesized. In specialized cells, the unneeded genes are heavily methylated and buried deep in the histones, likely never to be transcribed again.

The 3-dimensional shape of a histone can vary depending on chemical groups that can be covalently added depending on the degree of access needed to the gene associated with a particular histone. There are many chemical tags for histones, but the 2 best understood are methyl groups, which generally help the histone fold to hide the gene; and acetyl groups, which generally help the histone open up and make the gene more accessible.

There are enzymes that exist with job descriptions to either add or remove these methyl groups or acetyl groups to gene promoter sequences or histones, which in turn will be induced or repressed depending on the organism’s environment. At any given moment in time, an individual’s epigenome is unique and reflects the infinite number of events that determine what genes are turned on, or off, or somewhere in the middle.

Remember those identical twins that share 100% of the same DNA sequence? Epigenetic processes are already at work creating different expressions of this identical genome as soon as the shared zygote splits in 2 to create the twins.

, baby rats respond to stress differently (throughout their lives) depending on how much grooming and licking they receive from their mother in the first week of their life.

 Some mother rats provide abundant grooming and licking to their babies, while other mother rats are less interactive with their babies, paying less attention with significantly less grooming and licking. Research found that the baby rats that received plenty of grooming and licking during that first week of life remained notably calm when exposed to stressful situations as adults. Meanwhile, the baby rats deprived of their mother’s attention during the first week of life responded with distress when exposed to the same stressful situations as adults.

The researchers then swapped the baby rats at birth: Babies of low grooming/licking mothers were switched to mothers that were high groomers/lickers, and vice versa. Remarkably, the first week of life for the baby rats was the determining factor for stress response as adults, rather than any inheritance from their biological mother. In addition, the stress-tolerant adult rats had lower levels of cortisol, adrenocorticotrophic hormone, and corticotrophin-releasing hormone than the adult rats that were neglected during that first week of life. Further research demonstrated that the stress-tolerant adult rats had decreased methylation of their cortisol receptor gene, in contrast to the neglected rats. Hence, that initial increased grooming created an epigenetic change that resulted in a lifelong increased expression of the cortisol receptor, creating greater resilience to stress.

Can epigenetic modifications that occur during a person’s life be passed on to their offspring and future generations? From November 1944 through the spring of 1945 of World War II, the Germans, who controlled the Western Netherlands, set up a blockade that created a scarcity of food and severe starvation. From the detailed historical health care records, we have been able to study the long-term effects of the famine. Babies born to women who experienced starvation for the first 3 months of pregnancy and then resumed a normal diet when the blockade ended and food was available were likely to have a normal body weight at birth. However, babies born to women who were 6 months pregnant when the famine began were more likely to be underweight at birth.

These babies were followed by the health care system for decades. Remarkably, researchers discovered that the low-birth-weight babies continued to have body weights below average throughout their lives, including decreased rates of obesity as compared to the general population. The babies whose mothers experienced starvation during the first trimester of their pregnancy and had normal body weights at birth, had higher rates of obesity as compared to the general population decades later. Moreover, the grandchildren of the women who were starved during their first trimester also demonstrated some similar effects, suggesting a transgenerational inheritance.

One current hypothesis is that epigenetic changes to genes associated with nutrition and metabolism in the fetus would occur during a state of starvation to maximize the utilization of each calorie available. Significant epigenetic processes are in play during the first 3 months of fetal development, and these epigenetic modifications can then persist throughout life. Subsequent studies have shown that DNA methylation patterns in survivors of the Dutch Hunger Winter have demonstrated epigenetic modifications at genes involved in metabolism. The tragic circumstances of the Dutch Hunger Winter have provided a rare opportunity to study the potential effects of epigenetic changes early in life being passed on to future offspring. This is just one study; there is a growing literature in support of transgenerational epigenetic inheritance.

 for epigenetics in the National Library of Medicine generated 107,287 results, and 105,343 of these were published since the year 2000, demonstrating the explosion in this field over the past 2 decades.

Epigenetic modifications sculpt an individual’s phenotype 

 Epigenetic processes are most active, ubiquitous, and consequential throughout fetal development, as well as during the first 2 decades of life.

Returning to our identical twins, epigenetic differences are evident at birth, and these differences increasingly diverge throughout the twins’ lives. Research abounds comparing epigenetic profiles of individuals with and without a specific disease state to better understand the role of epigenetics in contributing to disease processes.

One significant consequence of the epigenetic contribution to phenotype is our growing understanding that genes that code for cytochrome P450 (CYP450) metabolic enzymes can be silenced or amplified, rendering the genotype of an individual’s CYP450 pharmacogenomic profile incomplete and unreliable. A recent study of CYP450 2E1 has demonstrated this 

 This growing understanding of the epigenetic effects on CYP450 gene expression calls into question the reliability of pharmacogenomic testing that reports a genotype, but does not factor in the epigenetic phenotype that ultimately will determine CYP450 metabolic enzyme activity.

Epigenetics has provided fertile ground to understand how early life experience can directly increase or decrease the risk and severity of psychiatric disorders such as schizophrenia, bipolar disorder, and 

The epigenetic paradigm shift has received relatively little attention compared to the human genome sequencing, despite the broad and significant impact it has had on our understanding of how environmental factors during a single lifetime can covalently regulate which genes are expressed, and to what degree, from the fixed human genotype. In fact, it is the epigenome that ultimately determines the individual’s phenotype for increasing or decreasing the risk of various diseases and the functioning of 

In the field of oncology, drugs that treat some cancers by epigenetic mechanisms are already FDA approved and in clinical use. Azacitidine and decitabine are both inhibitors of DNA Methyltransferase-1 and are approved for myelodysplastic syndrome—a disease of the bone marrow. Vorinostat and romidepsin both inhibit a histone deacetylase and are approved for the treatment of refractory cutaneous T-cell lymphoma. Time will tell if epigenetic modifying drugs will become part of our treatment arsenal in psychiatry.

In this issue we are delighted to present 2 important articles by Bursztajn et al expanding on the field of epigenetics. Their first article, “Harnessing Epigenetic Knowledge to Promote Resilience while Avoiding the Historical Pitfalls of Genetic and Social Reductionism,” provides a historical overview of the field of epigenetics, as well as offering some philosophical reflections. Their second article, “Transgenerational Transmission of Resilience After Catastrophic Trauma,” our featured CME article, explores the rapidly evolving understanding of the potential epigenetic role on resilience after severe trauma, and how this resilience may be passed along to the traumatized individual’s offspring.

is Medical Director, Brain Health, Exeter, NH; Editor in Chief, 

Staff Psychiatrist, Seacoast Mental Health Center, Exeter, NH; Consulting Psychiatrist, Exeter Hospital, Exeter, NH; Consulting Psychiatrist, Insight Meditation Society, Barre, MA.

1. Kronman H, Torres-Berrio A, Sidoli S, et al. Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons. 

2. Dempster EL, Pidsley R, Schalkwyk LC, et al. Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. 

3. Kular L, Kular S. Epigenetics applied to psychiatry: Clinical opportunities and future challenges. 

6. Kanherkar RR, Bhatia-Dey N, Csoka AB. Epigenetics across the human lifespan. 

7. Kronfol MM, Jahr FM, Dozmorov MG, et al. DNA methylation and histone acetylation changes to cytochrome P450 2E1 regulation in normal aging and impact on rates of drug metabolism in the liver. 

8. Blacker CJ, Frye MA, Morava E, et al. A review of epigenetics of PTSD in comorbid psychiatric conditions. 

9. Mazzone R, Zwergel C, Artico M, et al. The emerging role of epigenetics in human autoimmune disorders. 

10. Ling C, Ronn T. Epigenetics in human obesity and type 2 diabetes. 

Early-life stress can modify an individual's genetic code, leading to mental health problems later in life. But by understanding the science of epigenetics, psychiatrists can treat these conditions, and prevent intergenerational trauma. 

Exploring the Epigenetic Paradigm Shift

John J. Miller, MD, talks about treatment options for delirium. 

is medical director, Brain Health, Exeter, New Hampshire; Editor in Chief,

staff psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Exeter Hospital, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

Videos

What treatment options are available when dealing with delirium?

Pharmacological and Nonpharmacological Approaches to Delirium

John J. Miller, in the second episode of his series on delirium, discusses prevention. 

is medical director, Brain Health, Exeter, New Hampshire; Editor in Chief, 

What factors should be considered to help prevent delirium? 

Waxing and Waning: Preventing Delirium 

John J. Miller, MD, covers important topics in delirium. 

In the first episode of this new series on delirium, consider 3 crucial questions: What is it? How do we diagnose it? What do we do to work it up? 

Delirium: Criteria, Consequences, and Risk Factors

I often think back with fondness about clinical psychiatric practice in the early 1990s, a time when I could meet with patients for an hour weekly when indicated, and prescribing was as simple as choosing the medication I felt was most appropriate for the patient sitting in front of me. I feel sad for psychiatrists who completed their residencies after the year 2000 and have only known the burdensome 

 that currently dictate our options for the treatment of our patients.

There are many old dirt roads I could drive you down related to this topic, but I will limit this editorial to 3:

2. The loss of medication coverage when our patient changes health plans

3. The imposition of step therapy requirements by insurance companies

In clinical medicine, case reports have always provided the best vehicle for teaching, so I will share my experiences with patients over the past 5 years to exemplify these policies. These experiences are only examples of larger problems and trends, which regrettably contribute to 

. The medication-related elements of these cases are factual; however, I have changed patient characteristics to ensure privacy.

Decision Does Not Concern the Medical Necessity...

“Tom” is a 65-year-old divorced man who had an onset of 

 (OCD) and major depressive disorder (MDD) in his childhood years. I began treating him over 20 years ago, and after numerous and aggressive psychopharmacological trials he achieved significant symptom improvement in 2005 on sertraline 200 mg daily and ziprasidone 240 mg daily. Because of a medical comorbidity, he was eventually approved for disability.

At age 62, his health plan changed to Medicare, including Medicare Part D. Although Tom remained psychiatrically stable for 12 years on the combination of sertraline and ziprasidone, his first refill of the 

 following the institution of Medicare coverage was denied because it was not FDA approved for OCD or MDD. I was quite familiar with this occurrence and I did my due diligence by filling out a prior authorization form. It was denied. I appealed the denial, which was also denied. I appealed the second denial, this time advancing my now 13-page expedited appeal to Maximus Federal Services in Pittsford, New York. I explained in great detail Tom’s lifelong history of OCD and MDD, the numerous failed medication trials, and the significant pain and suffering Tom lived with until the sertraline/ziprasidone 

 provided symptom relief 12 years prior. Up to this point in my psychiatric career, I had never failed in my numerous prior authorization applications.

To my astonishment, the reply from Maximus Federal Services was:

“Geodon (ziprasidone) is requested for ongoing treatment of major depression and obsessive-compulsive symptoms, which are off- label (non-FDA approved) uses. You stated that the enrollee has been stabilized on this regimen and that discontinuation of treatment will result in a relapse of the noted conditions.

The Medicare-approved compendia do not contain any citations to support the use of the requested drug for treatment of the noted condition(s). Therefore, this drug is not being prescribed for a medically accepted indication as defined by Medicare law. Consequently, the noted drug is not eligible for coverage under Medicare Part D.”

Further, in their Explanation of Decision, they concluded:

“Our decision is the Plan is not required to cover Geodon. . . This decision does not concern the medical necessity of the requested drug. It only establishes if payment can be made under the Medicare Part D benefit.”

I was befuddled! The next step of appeal they offered was an Administrative Law Judge Hearing at the

. Tom’s elderly mother paid for the ziprasidone refills.

Subsequent to this frustrating precedent, I have had several denials of coverage of medications from Medicare, involving stable patients who were doing quite well on a chronic medication regimen but then, because they aged into their Medicare benefits, they lost coverage for their chronic but stable medication because it was not FDA approved for the prescribed diagnosis.

Patient Changed Health Plan, Chronic Coverage Denied

“Steve” is a 29-year-old single man who received a 

 7 years prior, at which time he was floridly psychotic with constant auditory hallucinations and paranoid delusions. After no symptom improvement over the next year with aggressive treatment with 4 different antipsychotic medications, he was hospitalized and treated with clozapine. Upon discharge, I gradually increased the clozapine dose, because of a lack of response, to his final maintenance dose of 800 mg by mouth at bedtime (with a 12-hour post dose serum clozapine level = 500 ng/mL). Over the following year, he significantly improved and has remained stable for the past 5 years, fully adherent with treatment. Although he continues with minimal daily 

, he understands them as a symptom of his schizophrenia, and he has learned to push them into the background and ignore them. Significantly, he has maintained the same full-time job for the past 4 years and lives independently with full functionality.

Early during the course of increased titration of the clozapine, Steve experienced 

 as a significant side effect. Ultimately, we began a trial of modafinil 200 mg by mouth twice a day, which significantly improved his daytime sedation and has allowed him to maintain full time employment. However, my first prescription for the modafinil was denied by his private health care plan because Steve did not have a diagnosis for the FDA-approved indications for modafinil of obstructive sleep apnea, narcolepsy, or shift work sleep disorder.

After my prior authorization was denied, I called the health care plan and requested a direct review with their pharmacist, which occurred 10 minutes later. The pharmacist agreed with my treatment plan of using the 

 to manage the sedation from the clozapine. It was smooth sailing for the next 5 years; I simply filled out a 1-page prior authorization annually, which was always approved.

Two months ago, Steve’s employer changed to a new health care plan, and the modafinil refill was denied coverage because of its off-label use. I have filled out 2 prior authorizations so far, and both have been denied. I requested a peer-to-peer review, but the plan denied this, stating they required a detailed written prior authorization request after the 2 initial denials before my appeal could be elevated to a peer-to-peer review. I am awaiting the plan’s response to my written appeal, and Steve is paying full price for the modafinil.

Step 1, 2, 3 . . . Then Maybe We Will Approve That Drug

“Susan” is a 34-year-old married mother of 2, who has struggled with recurrent episodes of 

 beginning in her early 20s. She initially responded to psychotherapy and healthy lifestyle changes, but by her mid-20s her depression had worsened, and we initiated antidepressant medication with good effect. Despite medication compliance over time, her depressive episodes recurred and she was treated with courses of 4 different antidepressants from different classes over a 2-year period with only partial response.

After discussing treatment options, and for many clinical reasons, Susan and I agreed to augment her fluoxetine with brexpiprazole 1 mg orally every day. I provided her samples for the first month, and she had a good response. When she went to fill her first prescription at her pharmacy, it was denied coverage. Susan’s insurance company would only cover the 

after documentation that she had failed trials of 2 other medications, which they listed as their required policy of so-called step therapy.

I could have lied, continuing to provide brexpiprazole samples, while telling Susan’s insurance company she was failing trials of the 2 required step therapy treatments, and eventually meet this insurance company’s step treatment failure. They would then allow coverage of the drug to which she responded. However, this is contrary to good medical practice, ethical behavior, and my general philosophy on life. Additionally, it would leave erroneous 

 in Susan’s medical record stating she failed trials of 2 step medications she never was really prescribed. I called the insurance company’s appeals department, was graciously transferred to one of the plan’s reviewing pharmacists, explained my clinical treatment plan, and the brexpiprazole was approved—a rare happy ending, albeit at the cost of lots of my time.

As I move toward the sunset of my career in clinical psychiatry, it saddens me to see how insurance companies—private, state, federal, Medicare, Medicaid, employer funded—have consistently obstructed physicians’ decision-making and treatment planning at every opportunity. It is exhausting, and it certainly contributes to physician burnout. Additionally, there is clear socioeconomic discrimination, as these policies are less expensive. Federal- and state-funded plans impose larger barriers to the treatment plans that the physician has determined to be best for their patient.

One of my primary frustrations with this process is exemplified by Tom and Steve’s stories: If we limit our prescribing to FDA-approved indications for medications, we will be in conflict with our oath to “do no harm” to our patients. The DSM diagnoses used for clinical trials’ inclusion criteria to demonstrate efficacy for FDA approval are actually mythological constructs in constant flux—although they do serve a useful purpose in creating a common language and approach to treating psychiatric disorders. An 

 highlighting this reality concluded that “only 11.8% of DSM-IV-TR diagnoses have an FDA-approved drug.”

 When DSM-5 was published in 2013, this percentage likely further decreased.

Ultimately, as experts in the field of psychiatry, we are being strong-armed by bureaucracies that use fictitious justifications to deny the implementation of our well-thought-through treatment plans for our patients. I have discussed this issue in detail in a 

 Additionally, a good clinician is skilled at identifying patterns of symptoms that consistently improve when using an FDA-approved medication for an unrelated diagnosis. The perverse obstructionism of insurance payers, based on ignorant and unethical justifications, further serves to undermine the quality of care that we attempt to provide to our patients.

With regards to Susan’s story of mandated step therapy by her insurer, although I was ultimately able to bypass the 2 required step medications, that process took a significant amount of time. In the United States, the intrusion of mandated step therapies has created quite a hardship for physicians in all specialties. A recent 

 nicely explored the current status of this insurance practice, and how slowly states are passing laws that attempt to push back on this intrusion.

Every day, medical literature articles appear documenting the contribution of the COVID-19 pandemic to physician burnout. Although this phenomenon is significant and pervasive, it is only one of many daily stressors contributing to physician burnout and the increasing incidence of retiring early from medical practice. I have reviewed 3 prescribing obstructions imposed intentionally by insurance payers that contribute to my own burnout; this has become more significant with each passing year. The difference is that COVID-19 is not willfully and consciously adding to my burnout, whereas the insurance companies are.

An analysis of the high psychotropic off-label use in psychiatric disorders: the majority of psychiatric diagnoses have no approved drugs

“Off label” does not mean “off limits.”

3. Krisberg K. Step therapy: Inside the fight against insurance companies and ‘fail first’ medicine. Medscape. Mar 26, 2021. 

https://www.medscape.com/viewarticle/948220

At almost every turn, insurance payers, based on seemingly ignorant and unethical justifications, continue to undermine the quality of psychiatric care.

Aiding and Abetting Burnout

John J. Miller, MD, invites you to join us for the hybrid model Annual Psychiatric Times® World CME Conference™ on September 30, 2021 through October 2, 2021. You can join via video call, or in San Diego, to earn CME credits. 

is Medical Director, Brain Health, Exeter, NH; Editor in Chief,

John J. Miller, MD, formally invites you to the Annual Psychiatric Times® World CME Conference™.

You're Invited!

John J. Miller, MD, discusses the potential psychiatric crises that can arise when practicing intense meditation. 

is medical director, Brain Health, Exeter, NH; editor in chief,

; staff psychiatrist, Seacoast Mental Health Center, Exeter, NH; consulting psychiatrist, Exeter Hospital, Exeter, NH; consulting psychiatrist, Insight Meditation Society, Barre, MA.

Meditation is a powerful practice with risks and benefits. On rare occasions, those risks can be extreme. 

Psychiatric Complications of Meditation Practice

John J. Miller, MD, talks about the increased risk of tardive dyskinesia on a synaptic level.

How could drugs that block post-synaptic dopamine 2 receptors increase the risk for tardive dyskinesia over time? 

Increased Risk of Tardive Dyskinesia 

John J. Miller, MD, guides us through a meditation session. 