John J. Miller, MD

Isolation does not mean disconnection. Our souls and spirits need to feel part of a bigger family-the human family. Dr John Miller shares his thoughts with his peers during these challenging times. Dr Miller is Medical Director, 

, Exeter, NH; Consulting Psychiatrist, Exeter Hospital, Exeter, NH; Consulting Psychiatrist, Insight Meditation Society, Barre, MA.

Articles

Isolation does not mean disconnection. Our souls and spirits need to feel part of the bigger family that we are. More in this video.

A Whole New Territory: Staying Connected in Real Time

send our thoughts, prayers, and best wishes to all. This is truly a global event that is impacting all of us in some meaningful way. As I write this on April 8th, in the US there are officially more than 400,000 cases of COVID-19, and there have been more than 14,000 deaths. 

 is currently ravaging through all 50 states, with half of the documented cases in just 2: New York and New Jersey. The country continues to grapple with a significant shortage of personal protective equipment and ventilators, and the national stockpile is now depleted.

My flight home from Denver to Boston on March 13th feels like forever ago. Even then the airports were eerily quiet, and an occasional traveler was wearing a mask. Arriving in Boston, my home airport where I spend a great deal of time, a heaviness filled the air of the terminal as travelers scurried about, everyone preoccupied and subdued. I was naively unaware of the impending catastrophic health crisis that had already seeded our country and was about to blossom into a life changing pandemic, the likes of which I had previously only read about in medical textbooks.

Today I saw a photograph that was simultaneously surreal and anticipated: a refrigerated truck parked next to a hospital in NY with the back door wide open as a recently deceased person wrapped in white sheets was being carried inside. The truck was lined with a 2 X 4 framed scaffolding built along each inside wall, with sheets of plywood serving as shelves in a makeshift morgue, each shelve wide enough and long enough to hold one person. Sadly, every shelf held a recent victim of COVID-19, wrapped in white sheets, with no time frame in place to allow for the preparation of a farewell ceremony.

As disturbing as this photo was, I am more disturbed by the lack of a national integrated and aggressive response to this pandemic in our great country. I realize it is easy for me to play Monday morning quarterback, but as I learn more and more about the information available to us in December, January, and February, I am befuddled by the inaction, lack of preparedness, and the minimizing of our national vulnerability to this pandemic as COVID-19 established its deep roots prior to emerging to assault us. Remarkably, and against the strong recommendation of all of the experts in the fields of infectious disease, epidemiology, and public health, today there remains a handful of states whose governors have chosen not to implement a shelter at home policy-the only intervention that has been shown to be effective in slowing down the ferocity of this pandemic.

Interestingly and appropriately, the narrative has become one of the US being at war with COVID-19. Let me say that again: the UNITED STATES is at war. Despite this, our federal government has adopted a policy of surrendering the command and control center to fight this war to each individual state. Imagine if we were being attacked through our Northeast border by an aggressive and ubiquitous enemy that began an assault on the states of Maine, New Hampshire, Vermont, and New York, and the federal response was to provide back-up as needed to each state, which were instructed to ward off the attack with their own resources. In my opinion, this is a fair analogy as to how this COVID-19 pandemic has been approached by the federal government. Regardless of political persuasion, a time of war demands a response by the US, not by each individual state, as our strength, strategy, and success in times of crisis has always resulted from our united federal approach to any threat.

A related issue is the dissemination of information to the public. When our country is under attack, it is imperative to engage and deploy the various experts whose collective knowledge and experience can coordinate a response that is most likely to succeed with the least number of casualties. If you or a loved one were to be diagnosed with a malignant brain tumor, with whom would you consult for treatment options and recommendations? Personally, I would consult with several expert neurosurgeons and neuro-oncologists. I would ask these experts to communicate their recommendations to my family and their reasonings. As a psychiatrist, physician, and scientist, I have spent my life developing an evolving expertise in psychiatric disorders and their treatment options. However, please do not ask me to evaluate and treat a cardiac arrhythmia, renal failure, pulmonary fibrosis, or anemia-rather, please consult with an expert in the appropriate specialty. The contradictions, misinformation, false hopes, and radically different recommendations on how to proceed through this pandemic are greatly amplified by marginalizing the experts.

A glimmer of light has been the innovative ways that the scientific experts, who are in the best position to advise state and federal policy in this pandemic, have found vehicles to communicate their assessments and recommendations. The current national challenge is to convince the policy makers and political leadership to govern based on the science and evidence-based facts-from our own scientific experts as well as experts in the international community, many of whom have significant experience in fighting this COVID-19 pandemic. On April 7th, American Medical Association President Patrice A. Harris, MD, MA, 

the National Press Club with the following message to maximize our national success in defeating COVID-19:

The AMA calls on all elected officials to affirm science, evidence, and fact in their words and actions. . . . We call on tech platforms to advance evidence-based information from credible sources and reduce the spread of misinformation.

COVID-19 has created massive collateral damage, the degree of which we cannot yet predict or fully understand. Sheltering in place, a necessary policy as we attempt to flatten the pandemic’s curve, has created an experience of isolation and disconnection at a time when we long for increased social contact and support. Hospitals, long-term care facilities, and other residential programs are banning visitors, which only serves to increase the anxiety and fear in us all. With this ban on visitors, families and friends are unable to be with their loved ones in their time of severe illness and approaching death.

It feels like our economy is also in the ICU, and financial vulnerability with the associated hard choices grow larger every day. Over the past 3 weeks, more than 16 million Americans have filed for unemployment, a staggering fact that was unimaginable just a month ago. As jobs are lost, many will also lose their health insurance benefits; access to necessary treatment and affordability of medications will become increasingly burdensome-likely leading to many unfilled prescriptions. It is not known what the long-term impact of our floundering economy will be once the pandemic subsides, or how quickly it can be rebuilt. We are likely in for a rough ride.

In psychiatric and medical practice, novel treatment delivery systems have emerged thanks to the commitment, innovation, compassion, and superhuman efforts of all members of the medical profession. As is the American way, citizens continue to rise to the challenges as they present themselves. By the time this editorial makes its way to print and into the hands of you, the reader, a lot more unknowable COVID-19 history will have been written.

As you read this, my sincere hope is that the pandemic will be loosening its choking grip. Many serious challenges will face us once the curve has been flattened, and we work as a nation toward recovery. Restoring our depleted medical resources, rejuvenating our overworked health care personnel, beginning to grieve the many losses that currently are necessarily on standby, establishing a safe return to work protocol, restoring jobs and income, and having the time to reflect on the personal and societal toll this pandemic has created will all happen in time.

There is still so much that is unknown: when will it be safe to resume social contact and gatherings; how do we deliver assistance to the financially depleted; will there be a second wave of the pandemic this fall or winter, and how do we best prepare for that; and how long will it take to restore our economy? Slowly, progress will be made toward developing medication treatments and vaccines, and our understanding of COVID-19’s biography will be published in the scientific journals. Ultimately, COVID-19 will write its own autobiography. As we move forward I hope that everyone whose lives have been affected by COVID-19 are able to begin to grieve the many, many losses in which we find ourselves submerged, and begin the long, slow process of recovery.

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.

Many serious challenges will face us once the curve has been flattened, and we work as a nation toward recovery in the war against COVID-19.

COVID-19: The Long, Slow Recovery

The classifications of medications into various groups was a helpful organizer in the early years of psychiatry. Identifying a drug as an antidepressant versus an antipsychotic versus an anxiolytic helped us quickly access a medication from a large armamentarium of psychotropics. Established effectiveness allowed clinicians to target a patient’s specific symptoms. In those early days we knew very little about pharmacodynamics, brain circuits, drug metabolism, the possible benefit or harm of a drug’s metabolites, and a drug’s receptor binding profile. The good news is that we have made tremendous strides in understanding each of these drug characteristics. We are now able to make more informed decisions about which drug to use for each patient with a particular diagnosis and specific comorbidities who is being prescribed an array of other prescription medications.

Regrettably, this significant expansion of knowledge about medications gets lost in the continued grouping of drugs by their old classifications. To keep the discussion focused, I explore the class of drugs that we typically call antipsychotics. Significantly, all current FDA-approved medications for the treatment of schizophrenia antagonize dopamine type 2 receptors (DR2)-but that is where their similarity ends. The antipsychotics in this larger grouping have remarkably different, and commonly unique, properties that can provide benefits but may have adverse effects or contraindications. Each of these antipsychotic drugs has a remarkably unique set of receptor binding affinities at a wide range of possible receptors that can assist in making informed choices about which medication to start with, how it will be dosed, how it should be cross-titrated with another antipsychotic, and how to maximize success in managing adverse effects.

The following is a list of some of the receptor properties that differ significantly from one antipsychotic to another:

Dopamine 2 receptor antagonist/partial agonist

Dopamine 3 receptor antagonist/partial agonist

Serotonin receptor antagonist (7 families of serotonin receptors with many subfamilies)

Serotonin receptor antagonist/partial agonist

Noradrenergic alpha 1, 2 (with sub-receptors of each) antagonist or agonist

Potency of each drug at each receptor: very potent, potent, moderate, weak, very weak

To be clear, we still do not understand all of the drug-receptor properties of any drug for the simple reason that we do not understand all of the receptor genes that reside in the human genome that have not yet been discovered or characterized. Additionally, as we see with the DR2, a gene product can be further processed by post-transcriptional editing (introns and exons) to provide a range of sub-sub-receptors with different binding affinities and circuitry locations (for example, the differing dopamine receptor 2 long [DR2L], which is postsynaptic, versus dopamine receptor 2 short [DR2S], which is presynaptic). To add an additional layer of complexity, each drug that is administered will likely be metabolized to chemically distinct molecules that will have their own unique set of receptor binding properties, which may contribute significantly or negligibly to the pharmacodynamics of the parent drug.

Chlorpromazine, discovered in France in 1950 as a derivative of an antihistamine, became the world’s first antipsychotic medication and was widely used in the 1950s. Interestingly, chlorpromazine has a diverse receptor profile, which includes activity at the dopamine 1, 2, 3, and 4 receptors, serotonin 2, 6, and 7 receptors, histamine 1 receptor, muscarinic acetylcholine 1 and 2 receptors, and the noradrenergic alpha 1 and 2 receptors. Subsequent members of this first-generation antipsychotic group included many drugs with variations of the chlorpromazine receptor profile-significantly all with activity antagonizing DR2s that surfaced as the mechanism necessary for these drugs to treat the positive symptoms of schizophrenia.

When clozapine was FDA approved in 1989, it became a paradigm changer, and it remains our most effective antipsychotic to date with the unique FDA indication for refractory schizophrenia. We still have no idea what receptor property or properties clozapine retains to provide this unique efficacy, but it ushered in a generation of novel medications-second-generation antipsychotics.

Honestly speaking, I disagree with this simplified nomenclature, as this descriptor suggests that all clozapine and post-clozapine drugs differentiate similarly from first-generation antipsychotics.

In my opinion, there are 3 post-clozapine families:

 Clozapine, olanzapine, quetiapine, and asenapine. All of these are more potent at the histamine 1 receptor than the D2 receptor, and all (with the exception of asenapine) have significant anticholinergic properties.

 Risperidone, paliperidone, ziprasidone, lurasidone and iloperidone. All of these are potent at the D2 receptor, have a wide range of unique binding profiles to various serotonin receptors, and all have some degree of activity at the noradrenergic alpha 1 receptor.

 Aripiprazole, brexpiprazole, and cariprazine. All of these are extremely potent antagonists at the D2 receptor-all three are more potent than all of the other antipsychotics-but also have partial agonism at D2 that renders their pharmacology different than all of the other first- and second-generation antipsychotics, which are pure antagonists. Beyond that, all 3 molecules have very different receptor profiles at other significant receptors.

We cannot generalize antipsychotics into one class of drugs

With this background, I would like to turn your attention to a recent publication in the February 2020 online issue of 

Effects of Antipsychotic Medication on Brain Structure in Patients With Major Depressive Disorder and Psychotic Features

 Voineskos and colleagues analyzed the cortical thickness in gray matter of 72 patients with major depressive disorder with psychotic features. Patients were treated with the sertraline/olanzapine combination for 12 to 20 weeks, including an 8-week period of remission of psychosis, as well as remission or near remission of depression.

This cohort was then randomized in a double-blind fashion to continue the combination regimen or to be switched from olanzapine to placebo (and remain on sertraline) for an additional 36 weeks. For the patients with sustained symptom remission at 36 weeks compared with the placebo-sertraline group, the olanza- pine-sertraline group demonstrated a significant decrease in cortical thickness. A decrease in cortical thickness was also seen in a post-hoc analyses of the patients who relapsed in the placebo-sertraline group compared with the group with sustained remission.

During the several weeks following its online publication, I have read many reviews of this article in various online psychiatric resources, all of which infer that the finding of this study is generalizable to all antipsychotics. Notably, and to the authors’ credit, they recognize a limitation to their study results:

Finally, our data were obtained with 1 specific antipsychotic, olanzapine, and it is possible they do not apply to other antipsychotics. However, based on the wealth of data demonstrating equivalent efficacy among antipsychotics and similar effects of different antipsychotics on brain structure in both animal and human studies, we speculate that our findings are likely to apply across all medications in this class.

The authors should have stopped after their first sentence. The second sentence, in my view, has no merit. “Equivalent efficacy” of olanzapine to other antipsychotics should not support a speculation about brain atrophy as an adverse effect. Moreover, their claim that the generalizability to all antipsychotics is further supported by “similar effects of different antipsychotics on brain structure in both animal and human studies” is also negated by their own claim that:

Concerning animal and uncontrolled human data suggest antipsychotics are associated with change in brain structure, but to our knowledge, there are no controlled human studies that have yet addressed this question.

Yes, they have now published the first controlled human study-but it is with a unique antipsychotic medication, which has a unique receptor profile that is not shared by most other antipsychotic medications. Hence, their study should pave the way for future studies that are randomized, double-blind, and placebo controlled, and which look at antipsychotics with different receptor profiles, or with receptor specific drugs to tease out which receptor(s) activity may be contributing to the decrease in human brain cortical thickness.

One possible explanation: anticholinergic receptor activity

Olanzapine contains anticholinergic receptor antagonism, which its FDA 2013 product insert lists as roughly 4 times weaker than its activity as a DR2 antagonist-relevant activity in the world of receptor binding properties. There is evidence showing that anticholinergic medication is correlated with increased brain atrophy. 

 evaluated data obtained from the Alzheimer’s Disease Neuroimaging Initiative of 402 cognitively healthy older adults divided into two groups: individuals taking drugs with medium to high anticholinergic effects (AC+) compared with individuals taking drugs with low to no anticholinergic effects (AC-). The researchers monitored cognition, brain metabolism, and brain atrophy over a mean follow-up of 32 months.

They reported that: “Reduced total cortical volume and temporal lobe cortical thickness and greater lateral ventricle and inferior lateral ventricle volumes were seen in the AC+ participants relative to the AC- participants.”

 monitored 723 subjects with a mean baseline age of 52.3 years from the Baltimore Longitudinal Study of Aging for a mean follow-up period of 20.1 years. They looked at the impact of long-term anticholinergic drug exposure on brain atrophy in cognitively healthy older adults. They concluded: “Long-term exposure to medications with mild AC (anticholinergic) activity during midlife is associated with increased risk of AD (Alzheimer disease) and accelerated brain atrophy.”

Clearly, much research remains to be done on many fronts. In my view, it is time to upgrade our nomenclature for drug classifications to a system more in line with the proposed neuroscience-based nomenclature (NbN). With this system, a drug’s unique molecular fingerprint would be apparent, and it would facilitate a well-needed transition to a more accurate nosology for drug classifications-one based on mechanism(s) of action rather than artificial and misleading categories.

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

1. Voineskos AN, Mulsant BH, Dickie EW, et al. 

Effects of antipsychotic medication on brain structure in patients with major depressive disorder and psychotic features: neuroimaging findings in the context of a randomized placebo-controlled clinical trial

. February 26, 2020; Epub.
	2. Risacher SL, McDonald BC, Tallman EF, et al. 

Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults

 2016;73:721-732.
	3. Chuang YF, Elango P, Gonzalez CE, Thambisetty M. 

Midlife anticholinergic drug use, risk of Alzheimer’s disease, and brain atrophy in community-dwelling older adults

All current FDA-approved medications for the treatment of schizophrenia antagonize dopamine type 2 receptors-but that is where their similarity ends.

Drug Receptor Profiles Matter

Are there any neuropsychiatric symptoms associated with the COVID-19 virus?

 It is early to speak with confidence about any real chronic aspects or consequences of the virus. There was a small 

recently looking at the people in China where the virus began, and they found the primary psychiatric symptoms were post dramatic posttraumatic stress 

(PTSD), because PTSD symptoms have to last for 30 days or longer. However, it is significant in a related fashion.

Not surprisingly, when you look at the SARS outbreak which was seemed to be a lot more dangerous and aggressive than the current COVID-19 virus, PTSD was the number one psychiatric complication both in health care providers and people who were affected by the virus. It seems like in some ways, not surprisingly, that this is a major life upheaval, and people are hypervigilant and that creates an experience of a traumatic intrusion. So, as of now, it seems like posttraumatic stress-like symptoms are the primary psychiatric comorbidity so to speak.

 How do you think this pandemic will impact psychiatry as a field?

What it is doing in our own clinic here in a matter of one week is where testing out the utility of having a virtual treatment model where basically we are able to interface with a lot of people without person-to-person contact, although telepsychiatry has been growing (in our clinic it hasn't been a big piece of what we do), in some ways this is going to be a real test of what is the utility what is the effectiveness of this of telepsychiatry and how does it make sense to fit in.

I do believe that although telepsychiatry is really important and helpful during this during this period of time, there are a lot of patients that I would still want to see in person and especially doing things like monitoring their metabolics in their blood pressure and pulse and doing an abnormal involuntary movement scale exams, and I personally find a lot of important information being with the person sitting across from me and seeing the body language and getting the big picture. My hope is it doesn't move us too far in the direction of telepsychiatry but that we find the useful niches for telepsychiatry and this is certainly going to put that to the test

Have more COVID concerns and clinical tips? Email us at 

. We may share your stories, queries, or thoughts in a future editorial or even as a standalone piece. Check out our 

Prevalence and risk factors of acute posttraumatic stress symptoms during the COVID-19 outbreak in Wuhan, China.

 March 10, 2020. medRxiv. doi:org/10.1101/2020.03.06.20032425.

2. Das DK. In China, COVID-19 Outbreak Leads to Posttraumatic Stress Symptoms. Psychiatry Advisor. March 17, 2020. 

https://www.psychiatryadvisor.com/home/topics/anxiety/ptsd-trauma-and-stressor-related/in-china-covid-19-outbreak-leads-to-posttraumatic-stress-symptoms

How will the coronavirus pandemic impact psychiatry as a field? Are there any neuropsychiatric symptoms associated with the COVID-19 virus? Those questions answered in this video.

Facing This Major Upheaval Together

In this video, John J. Miller, MD, discusses self-quarantine components of the COVID-19 pandemic with Heidi Anne Duerr, Associate Editorial Director of 

. Dr Miller is is Medical Director, Brain Health, Exeter, NH; Editor in Chief, Psychiatric Times; Staff Psychiatrist, Seacoast Mental Health Center, Exeter, NH; Consulting Psychiatrist, Exeter Hospital, Exeter, NH; and Consulting Psychiatrist, Insight Meditation Society, Barre, MA. He is Editor in Chief of 

What are you telling your patients regarding the pandemic both in terms of your office policies and preparing for self-isolation and quarantine as well as dealing with uncertainty?

I tell my patients the same thing I told my wife and my son and the same thing I tell my family and friends-that is, the situation literally is changing daily so stay tuned. I personally visit the CDC website on a daily basis so I am getting up-to-the-minute accurate information. In New Hampshire, we have a public health website that I also access daily to see what is happening in our state.

The big thing is staying inside, staying in the house, not going out, avoiding large crowds-the things you're hearing everywhere from everyone. The biggest challenge for us is convincing young healthy people to realize that even though they are at low risk, they may not even know they're infected. If they visit an elderly friend or parent or go to a store or someplace where other people are that are higher risk, they could be the transmitter of the virus.

It is really the action or inaction for all of us to protect each other. We need to think beyond our own needs and expectations and take care of the country as a whole. That is going to be one of the biggest challenges-convincing the young and the healthy to flatten the curve and prevent more infections regardless of their own risk.

Are you seeing more panic and anxiety in your patients at this time or are things pretty much the same?

 A few of my patients who have significant anxiety disorders are actually doing quite fine with it. They say they have been dealing with anxiety all their lives, and for them, they are seeing people who are not normally anxious get nervous. Now that us just my own experience with a few patients and I'm sure it's going to differ everywhere you go. I’ve found that initially I was surprised by that, but the other side of the coin is whenever you delve into the unknown and you're not expecting it, anxiety is going to be there.

 What do you think the impact of self-isolation and everybody working at home is going to be in the long run?

To start out on a light note, I read an article that said that the population that is having the most difficult time adjusting are all the pets at home. Our dogs and cats and birds and fish wonder if something different is going on because everyone is around.

On the more serious side, households where one or both of the primary adults are usually working and out of the house during the day, children and adolescents are at school, and young adults are working or in college-all of a sudden everyone is home taking virtual classes or working in virtual environments. So now you have a whole new kind of family culture that has developed literally overnight. Instead of everybody having schedules and a lot of time away, everyone is in a small contained area, probably fighting for the computer screens. Everyone is trying to do things virtually. I can only imagine that in some situations, it is going to be incredibly stressful.

It is going to be a good opportunity here for family self-therapy, learning to work together and cooperate and how to re-experience the core family just being with itself all the time. So there is a silver lining in there, but it is a huge adjustment. It is going to be very stressful and we still don't know how long this will continue, which I think is another piece of stress.

This is a whole new virus the experts don't know about, yet it is a slow learning process. We all have to be patient and respectful of what is asked of us and appreciate the hardworking commitment of the scientists and the epidemiologists. We then follow on the directives of the primary health care providers that are getting their mandates from the people who are overseeing the whole management of this pandemic.

What do we tell patients regarding the pandemic both in terms of office policies and preparations for self-isolation and quarantine as well as dealing with uncertainty?

Preparing and Helping Patients Deal With Self-Isolation

Imagine if you or a loved one was diagnosed with cancer, and your oncologist had not learned about any new medications related to treatment of this cancer for the past 5 years? What if your family member with a stable psychotic disorder developed severe tardive dyskinesia and, as a result, would not leave their group home due to embarrassment about these involuntary movements, and their prescribing clinician had no knowledge of the two drugs that were FDA approved to treat this movement disorder in 2017?

I love psychiatry, I love biochemistry, and I love learning. These passions collide in the arena of new drug development, which continues to deliver novel drug mechanisms of action throughout the field of medicine. In 1986, as I began my internship at the Medical Center Hospital of Vermont, with the gift of an outstanding psychopharmacology mentor, John Ives, MD, I was able to confidently learn to prescribe all the psychiatric medications in our armamentarium at that time. To be fair, the list was rather short: monoamine oxidase inhibitors, tricyclic antidepressants, benzodiazepines, antihistamines, anticholinergics, antipsychotics, lithium, carbamazepine, valproate, and a few others.

During my internship year, I was taught the pharmacology and FDA approval indications for two new psychiatric drugs: bupropion (which was approved on December 30, 1985 for the treatment of major depression) and buspirone (which was approved for the treatment of generalized anxiety disorder in 1986). These drugs had novel mechanisms of action and immediately were added to the hospital’s pharmacy formulary for the treatment of inpatients.

In my years of adult psychiatry residency at the Department of Psychiatry at the University of Massachusetts Medical Center in Worcester, two additional medications were FDA approved that revolutionized treatment options for many of our patients: fluoxetine and clozapine. A game changer for our patients with schizophrenia, clozapine was FDA approved in 1989 for refractory schizophrenia. Clozapine served as a paradigm shifter, and it remains the most effective treatment for refractory schizophrenia. Additionally, it prompted receptor-directed research on novel agents that would modulate serotonin along with dopamine receptors for the treatment of psychosis and mania. Within months of its FDA approval, under the guidance of my psychopharmacology supervisor, I crossed titrated a patient with refractory paranoid schizophrenia from high dose perphenazine  to clozapine. Meanwhile, my very first educational seminar on how to dose clozapine, and the important risks/benefits/side effects that I needed to understand before prescribing this novel drug, was presented by the pharmaceutical representative from Sandoz, who also provided me with a host of peer-reviewed, published clinical trials and information on clozapine.

In 1995, while an assistant professor of psychiatry at the University of Massachusetts Medical Center, I was invited to join the speakers’ bureau for a pharmaceutical company. During the subsequent 25 years, I have proudly maintained ongoing consultation collaborations with pharmaceutical companies that are focused on developing new medications with novel mechanisms of action as well as medications with improved efficacy and tolerability as compared to similar medications currently available. Once FDA approved, I continue to enjoy educating psychiatric colleagues on information important to any prescriber of a new medication: pharmacokinetics, pharmacodynamics, clinical trial results, approved indications, risks, benefits, and side effects.

Although there are many critics of physicians who collaborate with the pharmaceutical industry, I judge myself based on the feedback from the clinicians to whom I present this information. Of course, I always disclose any potential conflicts of interest when presenting a lecture or authoring a publication, which is essential.

During my tenure as a psychiatrist, I have been impressed and invigorated by the dedicated research and development in the pharmaceutical industry as well as their commitment to further understanding disease states and identifying novel medications that serve to decrease symptoms and improve the quality of life of our patients. A great example was the simultaneous FDA approval of two novel medications in 2017 for the treatment of tardive dyskinesia, a movement disorder caused by chronic exposure in a part of the brain to dopamine-2 receptor blocking agents (including all of the antipsychotics). Although tardive dyskinesia was identified in the late 1950s, and for many of our patients causes significant functional impairment, we had no treatment for it until these two medications were approved. Outside of psychiatry, the specialties of neurology, oncology, hematology, immunology, endocrinology, gastroenterology, and others have had spectacular breakthroughs in novel treatments that literally have been life-saving.

As clinicians with the opportunity to prescribe life-changing medications for our patients, I believe it is important to understand our biases, both positive and negative, towards Pharma. One benefit from lecturing around the country is the opportunity to meet and speak with psychiatrists, nurse practitioners, and psychiatric providers of all types, and to hear their experiences and challenges in various treatment settings. As a believer in immediate access to all new information that may improve the quality of patient care, it has been disheartening to consistently hear for more than 15 years about the pervasive culture at many medical centers and health care systems to ostracize the pharmaceutical industry, and not uncommonly, to threaten to fire employed physicians and clinicians who would like to attend educational programs about new medications on their own free time.

Some generalized recurrent themes include:

âº Psychiatric residents who sneak out to a lecture on a new drug express frustration that the attending/supervising psychiatrists with whom they work have no knowledge of new medications that have been FDA approved over the past 5 to 10 years.

âº A psychiatrist at a major medical center/teaching hospital who was fearful to attend a lecture program about a new medication because they were told that they would be fired if they attended any pharmaceutical industry sponsored educational program-even though it was after hours and on their own time.

âº Major medical centers/health care systems banning pharmaceutical company representatives, including highly trained medical science liaisons (usually medical doctors or doctorate level pharmacists who receive no remuneration for any resulting business, rather acting  purely as a scientific resource) from even entering their buildings.

âº A student with only two months remaining before completing her psychiatric nurse practitioner program at a New England teaching hospital attended a pharmaceutical company-sponsored program where she first learned about a medication that has demonstrated some unique properties helpful for a sub-population of patients and that was FDA approved more than four years ago.

âº Psychiatrists at a busy community mental health center express frustration that when their patients were admitted to several different inpatient psychiatry units, the “newer” medications were stopped, and their patients were discharged on an array of side effect-ridden older medications because they were the only options available on the hospital’s pharmacy formulary.

âº Frontline prescribers are not allowed to accept medication samples from pharmaceutical companies at risk of job termination. This is unfortunate for many reasons; in my view, the biggest reason being a lost opportunity to have a month trial, at no cost, on a medication to see if it is effective before providing a prescription that will likely require an accompanying nightmarish prior authorization form.

When I reflect on the rich learning opportunities and experiences I have had in my role as a consultant and lecturer for various pharmaceutical companies over the past 25 years, I remain befuddled as to why many of our major medical centers/residency training programs/health care systems continue to ban the pharmaceutical industry from having any communication with their treatment providers. The majority of physicians and pharmaceutical companies, myself included, all agree that during the 1990s the relationship between the pharmaceutical industry and prescribers was out of control. Too much money was being thrown around with no clear guidelines and embarrassing conflicts of interest. Appropriately, in the early 2000s, there was a major restructuring of how prescribers and the pharmaceutical industry interfaced. As one would expect, initially the pendulum swung too far in the direction away from collaboration. In my opinion, the tragedy is that it has continued to swing away from ethical and appropriate collaboration to the current culture where the pharmaceutical industry is often demonized and ostracized.

Sadly, the real victims here are our patients. When the faculty that is training the next generation of clinicians intentionally avoid learning about new medications, and do not utilize novel treatments because of some misperception of greedy collusion with pharma or insecurity that they will be judged by their peers as unscrupulous, the standard of care will be steadily lowered and our oaths to “Do No Harm” will be broken.
	The United States has always been a fertile field for discovery, research and development, and innovation in all markets, including the pharmaceutical industry, hospital systems, medical device development, and the delivery of quality health care. Many of these markets require a margin of profit to survive in our country’s economic structure. This profit motive is primal and necessary for continued operations, but it does not necessarily equate with sinister motives and rogue manipulations. Every bushel from the orchard is likely to have one rotten piece of fruit, but we do not discard the entire bushel as bad.

Our profession is one of lifelong learning, and that fact creates a responsibility to remain up to date on new and expanding treatments specific to our specialty. Any new treatment is initially vetted by the FDA or other regulatory agencies. Once a novel treatment is available to us frontline clinicians, our due diligence should include an objective appraisal of this new treatment, being mindful of positive as well as negative biases that may intrude into our assessment, so we may determine when and how the new treatment may fit into our constantly evolving armamentarium.

In an ideal world, clinicians would be provided sufficient and mandatory time each week to research and learn about newly available treatments. My observation is that, despite good intentions, the stresses of a busy schedule, onerous documentation, returning phone calls, reviewing lab work, and conducting other patient-related correspondence ultimately collude to exhaust us by the end of the day. In this current climate, spending time with a pharmaceutical representative or attending a lecture program by a physician consultant may provide an efficient vehicle to learn the basic data and FDA-approved facts that we can then ponder, discuss with colleagues, and ultimately make our own informed decision about the potential role of new treatments in our clinical practice.

The current political climate in the United States is teaching us about the dark side of extreme partisanship-such partisanship should not exist in our honorable profession of medicine. I would suggest that it is time to reassess the black and white polarization that many academic and medical systems have erected against the pharmaceutical industry and that we resume collaboration in a manner that provides our patients with the best possible treatments. I wonder how many years would have passed before I prescribed clozapine if I never attended that in-service by the clozapine sales representative during my residency?

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

It can be disheartening to hear about the pervasive culture at many medical centers and health care systems to ostracize the pharmaceutical industry, and not uncommonly, to threaten to fire employed physicians and clinicians who would like to attend educational programs about new medications on their own free time.

Reframing Our Relationship With Pharma

As we navigate uncharted waters on the pandemic front, John J. Miller, MD, shares his thought about this important topic and what he is both professionally and personally. Dr Miller is is Medical Director, Brain Health, Exeter, NH; Editor in Chief, Psychiatric Times; Staff Psychiatrist, Seacoast Mental Health Center, Exeter, NH; Consulting Psychiatrist, Exeter Hospital, Exeter, NH; and Consulting Psychiatrist, Insight Meditation Society, Barre, MA. He is Editor in Chief of Psychiatric Times.

Heidi Anne Duerr, MPH (HAD): What are you doing differently during this pandemic both professionally and personally?

 On the personal front, I'm doing what we all have been encouraged to do, which is basically staying at home. I did I work Monday at our clinic, which is right in the town I live, and I worked all day. A little over half of my scheduled patients showed up but, from that point forward and virtually on a daily basis, we are continuing to modify clinic policies to minimize risk and maximize safety for everybody.
	Professionally, one of the big things for us was the canceling of the annual American Psychiatric Association Meeting. It is always a great meeting. You get to collaborate, see lots of colleagues, and we have our Psychiatric Times meeting there. All of that that was cancelled on Sunday night and we have to put safety ahead of everything else-so that's where we stand.

How have things changed for you in your clinic over the past few weeks?

 We have an excellent team from our CEO right down to the psychiatrists and the nurses and all the team leaders. We have about 260 employees. We have two clinical sites, one in the town where I live and one about 15 miles away. We see about 6000 patients in total and so it is a pretty large population. Our team goes out on a daily basis to see high-risk patients; we have case managers that do things like bring patients to appointments or grocery shopping or checking in. We have outreach therapists that go to go to clients’ houses and will actually do therapy right in the house if patients have trouble getting into the clinic. We go into the school systems and we do consults at the local hospital.

We cover the emergency department, so we are pretty big system and we traditionally have been opened 8:00 AM to 8:00 PM Monday through Thursday and all day Friday. So just in this past week, there have been literally daily changes in response to the dynamic situation here at the beginning of the week here in New Hampshire. I believe we had 12 confirmed cases and now we are at just over 30 confirmed cases, so we're a small state but the numbers are slowly heading up as they are everywhere.

Some of the big changes we have enacted this week is we are limiting our clinic hours to shorter periods of time and then a major change at both clinics before anyone can come in the front door, they have to go through the CDC-recommended screening questions. If there is any concern or possibility that the person might be infected, we ask them not to come into the building. We then give them appropriate options as alternatives.

Secondly, an important and necessary decision is we do a lot of intramuscular injections for long acting injectables and other various medications. The psychiatric nurses at both clinics have developed a protocol where they are only going to do injections half a day on Tuesdays and Thursdays, whereas before it was pretty flexible. Before, the case manager could bring patients in when it was convenient or when there was an appointment, but now we have those very clear limited times that patients will be able to come in and get their injections, again as long as they pass that screening before they enter the clinic.

The biggest changes the clinic is aggressively working with our excellent IT team to roll out a platform like Zoom. It is one of the platforms are we using as well as Telepsych. We are going to do as much direct patient care as we can, so case managers, therapists, outreach specialist, psychiatrists, nurse practitioners, and psychiatric nurses that whenever possible, at least for the foreseeable future, we will be doing as much telepsychiatry as we can so that will be able to deliver our treatment for our patients but at the same time maximize safety and through isolation and kind of reinforcing the importance of the self-quarantine.

As we navigate uncharted waters on the pandemic front, John J. Miller, MD, shares his thought about this important topic and what he is doing differently both professionally and personally.

Patient Care in the Age of COVID

L-methylfolate is commonly presented as a safe augmenting agent to patients with antidepressant non-response in unipolar depression with virtually no side effects. Although this is likely to be true most of the time, as with any treatment, there are risks that can be significant albeit rare. Currently, there is a paucity of published literature of double-blind placebo-controlled randomized clinical trials of the efficacy and tolerability of L-methylfolate in both unipolar and bipolar depression. This article discusses the rationale and history of L-methylfolate use in such patients, and then shares three cases that collectively suggest L-methylfolate may contribute to agitation and mania.

In humans, folate (ie, Vitamin B9) is one of 13 essential vitamins. Low serum folate and low red blood cell (RBC) folate levels are independent risk factors for major depressive disorder (MDD); they also are associated with more 

 Maternal folate deficiency prior to conception and throughout pregnancy has been 

to increase the risk of neural tube defects and congenital abnormalities in the developing fetus, as well as peripheral neuropathy and anemia in the mother.

Ongoing studies in psychiatry and obstetrics support the use of oral dosing with the bioactive form of folate, L-methylfolate. L-methylfolate is FDA approved as a medicinal supplement for 

 The use of L-methylfolate allows the clinician to bypass a critical metabolic step in folate’s transformation to L-methylfolate, specifically the reduction of methylenetetrahydrofolate to L-methylfolate by the enzyme methylenetetrahydrofolate reductase (MTHFR). MTHFR is the rate limiting step in this process, and significantly, MTHFR enzymatic activity has a wide range of function depending on its genetic polymorphisms at three nucleic acid sites, the most significant being: C677C (good activity), C677T (decreased activity), and T677T (poor activity).

L-methylfolate is the only form of folate that can cross the blood-brain barrier, where it plays an essential role in the one carbon cycle metabolic pathway that is 

for the production of the monoamines serotonin, dopamine, and norepinephrine.

 undertook a randomized study of L-methylfolate as adjunctive therapy in patients with MDD who had a partial response or no response to selective serotonin reuptake inhibitors. A population of 75 patients were treated for 60 days with 15 mg L-methylfolate daily. The findings indicate that L-methylfolate was significantly more effective as compared with placebo. The response rates were 32.3% in the SSRI plus 15 mg L-methylfolate group compared with 14.6% in the SSRI plus placebo group.

The number needed to treat to achieve response with the addition of 15 mg L-methylfolate to an SSRI was 6. Overall L-methylfolate was well tolerated with minimal adverse effects; manic symptoms developed in one patient in the L-methylfolate/SSRI group, which resulted in patient discontinuation.

A subset of the original acute treatment cohort was followed in a 12-month open-label continuation 

 during which outpatients were treated with 15 mg L-methylfolate and an SSRI.

 The researchers reported “high rates of response, remission, and recovery,” as well as overall safety, tolerability, and a good rate of retention.

Unfortunately, there is a paucity of research into the use of L-methylfolate to treat bipolar I depression (BD-I). To address this unmet need, 

 created an open label registry of patients with bipolar depression. The patients received treatment as usual as well as 15 mg L-methylfolate daily for 6 weeks. Pre-study medications included lithium, lamotrigine, quetiapine, valproate, lurasidone, levothyroxine, Dexedrine, and extended release methylphenidate. At week 6, there was a 50% or greater improvement on the Montgomery Asberg Depression Rating Scale, with a pre-treatment mean score of 23.4 and a post-treatment score of 13.9 in six of the 10 patients studied. Significantly, the researchers noted that one patient had “an exacerbation in YMRS (Young Mania Rating Scale) and a possible manic episode.”

With that in mind, we present three case vignettes of women with affective disorders, two with MDD and one with BD-I. All three had acute symptoms of agitation shortly after augmenting their divergent psychotropic medication regimen with 15 mg of L-methylfolate. In all 3 cases, the agitation rapidly improved upon discontinuation of L-methylfolate.

“Jesse” was a 63-year-old married white woman who was on disability for multiple sclerosis. She struggled with treatment-resistant MDD for several years, with no evidence of a bipolar diathesis. She received numerous antidepressant medication trials, including therapeutic doses of phenelzine, fluoxetine, sertraline, nortriptyline, escitalopram, mirtazapine, venlafaxine, vilazodone, vortioxetine, and duloxetine; all of which failed.

Pharmacogenomic testing of the MTHFR gene was consistent with decreased activity of this enzyme (C677T). It was decided to augment duloxetine with 15 mg L-methylfolate daily.

After several days on this regimen, her husband called to report that she had become uncharacteristically irritable and agitated. No identifiable situational stressors, substance use, new medication, or medical illness could be identified. Her long-term medical history was significant for multiple sclerosis, hyperlipidemia, osteoporosis, neurogenic bladder, and hypertension.

Shortly after discontinuing the L-methylfolate, the irritability and agitation resolved. Upon obtaining further history, the patient reported a hypomanic-like adverse effect from previous prednisone treatment. There was no other history of bipolar spectrum symptoms.

“Leslie” was a 43-year-old married white woman who presented with a history of treatment-resistant MDD with multiple antidepressant failures. The trials included imipramine, paroxetine, sertraline, escitalopram, duloxetine, venlafaxine, and fluoxetine. Her medical history was significant for multiple sclerosis, asthma, and migraines. She was taking venlafaxine XR 225 mg for an adequate duration, but there was a suboptimal response of her depressive symptoms when the 15 mg L-methylfolate daily was added. Upon follow up six weeks later, she reported that her experience with the L-methylfolate was horrible, describing herself as feeling “agitated and aggressive.”

“Susan” was a 56-year-old divorced white mother with a longstanding history of bipolar disorder who presented with an episode of depression. She had had previous episodes of mania, complicated mania with psychosis, and depression as well as several inpatient psychiatric hospitalizations for repeated manic episodes and psychotic symptoms; her most recent hospitalization was more than 15 years prior to the current episode of depression. Over the previous several years, her symptoms were reasonably well-managed on a combination of carbamazepine and oral/depo injection haloperidol. Chronic residual symptoms included a notably flat affect, anhedonia, and a largely depressed mood at baseline.

Pharmacogenomic testing was performed as part of her work up, and it revealed that her MTHFR gene tested homozygous (T677T), which suggested poor enzymic activity. A trial of 15 mg L-methylfolate daily was initiated to target recalcitrant depressive symptoms.

The patient called a few days after L-methylfolate initiation and described feeling unwell, agitated, and seeming to be a bit paranoid. She was instructed to discontinue the L-methylfolate, and these symptoms resolved within a few days. She reported that she quickly felt more like herself after discontinuing the L-methylfolate. She described the brief trial as horrible and stated that she “will never take it (L-methylfolate) again.”

These case vignettes suggest that patients with unipolar or bipolar depression may be at risk for the onset of agitation shortly after beginning a trial of 15 mg L-methylfolate. In all three cases, the agitation resolved a few days after discontinuing the L-methylfolate, supporting the likelihood that it contributed to the agitation. It is interesting to note that the two patients with MDD both had a comorbid diagnosis of multiple sclerosis. This, however, may very well be coincidental.

The findings presented are preliminary and are presented with the aim of raising clinicians’ awareness that L-methylfolate may contribute to symptoms of agitation, irritability, and possibly hypomania, mixed mania, or mania in susceptible individuals. The only concrete conclusion that can be drawn is that well-designed clinical trials are needed to ferret out the rare but potentially significant adverse events associated with L-methylfolate.

There are no clinical data on the risks/benefits/adverse effects of the use of L-methylfolate off label in the treatment of bipolar depression. This is a significant lack of information, because many patients who ultimately have a diagnosis of bipolar disorder are initially treated-sometimes for years and even decades-for unipolar depression. The study by 

 demonstrated that 7.5 mg of L-methylfolate performed no better than placebo as an augmentation agent in patients with MDD who did not respond to SSRIs, whereas 15 mg per day of L-methylfolate significantly separated from placebo. The dose response of L-methylfolate for effectiveness and adverse events in BD-I is unknown.

Future studies to assess the clinical consequences of augmenting antidepressants with L-methylfolate should include:

1. Large placebo controlled clinical trials

 of both unipolar depression and bipolar depression to determine the number needed to harm in the different patient populations, as well as the number needed to treat in bipolar patients.

2. Augmentation of non-SSRI antidepressants

 with L-methylfolate to determine if the improvement seen in MDD when SSRIs are augmented with L-methylfolate are generalizable to all antidepressants.

3. An evaluation of the L-methylfolate dosage range

 in patients with bipolar depression to determine which dosages (3.75 mg, 7.5 mg, 15 mg) are helpful and which are harmful.

These three cases illustrate the rare but possible adverse effects of agitation, irritability and possible onset of hypomania with adjunctive L-methylfolate. The publications reviewed report one patient who developed manic symptoms while taking L-methylfolate/SSRI for unipolar depression,

 and one patient who developed an increase in the YMRS and a possible manic episode when L-methylfolate was added to the regimen treating the underlying bipolar disorder.

 This activation by L-methylfolate is consistent with its putative mechanism of action, specifically increasing brain levels of norepinephrine, dopamine, and serotonin.

L-methylfolate, the bioactive form of folate that crosses the blood-brain barrier, has been shown to effectively augment SSRIs in patients with MDD who did not respond to SSRI monotherapy; and it also has been shown to be generally well tolerated. Its role in augmentation in bipolar depression remains to be determined. Although the current data are limited, clinicians and patients should be aware of the possibility that L-methylfolate may increase agitation and may contribute to the onset of hypomania/mania.

 is Psychiatric-Mental Health Nurse Practitioner, Seacoast Mental Health Center, Portsmouth, NH; and Clinical Assistant Professor, Department of Nursing, University of New Hampshire, Durham, NH; 

 Staff Psychiatrist, Seacoast Mental Health Center, Exeter, NH; Consulting Psychiatrist, Exeter Hospital, Exeter, NH; and Consulting Psychiatrist, Insight Meditation Society, Barre, MA. Ms. Robinson and Dr Miller indicate they have nothing to disclose regarding the subject of this article.

1. Papakostas GI, Cassiello CF, Iovieno N. 

Folates and S-adenosylmethionine for major depressive disorder

2. Alpert JE, Mischoulon D, Nierenberg AA, Fava M. 

Nutrition and depression: focus on folate

Folic acid supplementation and pregnancy: more than just neural tube defect prevention

Treatment-resistant depression: recent developments and future directions

5. Stahl SM. Novel therapeutics for depression: L-methylfolate as a trimonoamine modulator and antidepressant-augmenting agent. 

6. Papakostas GI, Shelton RC, Zajecka JM, et al. 

L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials

7. Zajecka JM, Fava M, Shelton RC, et al. 

Long-term efficacy, safety, and tolerability of L-methylfolate calcium 15 mg as adjunctive therapy with selective serotonin reuptake inhibitors: a 12-month, open-label study following a placebo-controlled acute study

8. Nierenberg AA, Montana R, Kinrys G, et al. 

L-Methylfolate for bipolar I depressive episodes: an open trial proof-of-concept registry

Experts discuss the rationale and history of L-methylfolate use in patients, and then shares three cases that collectively suggest L-methylfolate may contribute to agitation and mania.

L-Methylfolate: Augmenting Agent May Contribute to Agitation and Mania 

One of the challenges in primary care and in psychiatry is determining when we meet a new patient who presents with a “classic” major depressive episode whether that episode is in fact unipolar depression or bipolar depression.

In terms of the diagnostic lists of symptoms, they are identical for both conditions, but the treatments are very different. Over the past decade, a lot of time has been devoted to education and to help clinicians make assessments at that first evaluation.

The better we are at diagnosis, the better the treatment outcomes, and the better the functionality of the patient. There will be fewer adverse effects and possibilities of mood switching. It surfaces an important area and we are working hard to better approach diagnosis and treatment.

Dr Miller 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. He is Co-Chair of the Annual Psychiatric Times® World CME Conference™, October 15, 2020 – October 17, 2020. Please visit the following link for more information: 

When we meet a new patient who presents with "classic" symptoms, there are challenges described in this brief video.

Screening and Diagnostic Approaches for Bipolar Disorder

When I was applying to medical schools in 1981, my most memorable experience occurred at the University of Vermont Medical School when, on the morning of the interviews, about 20 applicants met with the Dean of Students. She got right down to business. The Dean started by stating that the field of medicine is one of lifelong learning and, every 5 years 50% of our knowledge base changes in some meaningful way. She concluded by inviting any of us who felt unable to honor this career-long imperative of continued learning to leave before interviewing, as medicine was not the career for that person.

Once I began medical school and throughout residency, there was no paucity of new information. To use a common metaphor, most days I felt like I was trying to drink as much water from the open fire hydrant flow as I could, watching most of the knowledge flow right past me. After residency there was nightly and weekend studying to prepare for the written and then oral boards.

Completing board certification was a moment I will always relish- learning could now be on my terms. When I decided to leave academia in 1995 and begin a career in private practice and community psychiatry, I experienced an unexpected feeling of loss, not having realized the tremendous immersion in daily learning that academia had provided.

I was delighted to discover a vast array of self-education resources in various multimedia formats, and these resources have steadily grown and diversified over the ensuing 25 years. Live conferences play an especially important role, as they allow for the intermingling of colleagues, which enriches learning in many ways. Additionally, reconnecting with colleagues socially and making new acquaintances serves to enrich our experience and support ongoing collaborations. Attending a conference where we are insulated from our usual responsibilities, and we are able to focus solely on expanding our acumen with the most up-to-date information in psychiatry commonly reignites our excitement and enthusiasm, which provides the nourishment to return to and continue in our day-to- day clinical practice.

 to provide a monthly publication accessible to all psychiatric practitioners that would ensure continued cutting-edge articles across the entire landscape of psychiatry. Not coincidentally, Dr Schwartz was also the founder of CME, Inc, which in 1985 was “the largest independent provider of psychiatric meetings in the United States . . . conducts Advanced Psychiatric Updates-continuing education programs for psychiatrists at which the country’s leading experts make in-depth presentations to practitioners.” (

; January 1985; Vol. I; No. 1, page 1). Each issue of 

Editor in Chief John Miller, MD, shares his insights on the upcoming Psychiatric Times World CME Conference in October.

Author | John J. Miller, MD