Friday, October 17, 2014

Being Honest Won't Save You - Lessons In Medical vs. Business Accountability

Every now and again I flash back to a surgical rotation that I was doing at an old county hospital.  It was quite run down.  We had a large surgical service comprised mostly of people with gunshot wounds, cancer patients, and people who were in long term care hospitals for mental illness who developed acute surgical problems.  Most of the patients who had gunshot wounds had been shot by the police and they had police officers posted outside of their doors.  On some days it seemed like there were a lot of police officers outside of every other door for quite a distance down the hallway. We did two sets of rounds - in the morning after the surgical procedures and another set of rounds at about 6 or 7 PM.  The evening rounds always ended under fluorescent lights in what is probably a long abandoned nurses station.  In this particular case we are rounding with a senior surgeon and a junior surgeon.  The senior surgeon has just demonstrated how much he knew and how little the residents knew about the effects and importance of gastrointestinal tract hormones.  After a few moments of uneasy dead air, the junior staff asks the intern: "What was Mr. X's calcium level this afternoon?"  The labs were typically run at 4PM and in those days we would have started to see results at about 5 or 5:30, but we were all rounding at that time and attempting to answer questions about GI hormones.  The conversations went something like this:

Staff MD:  "What was Mr. X's calcium level this afternoon?"
Intern:  "I don't know."
Staff MD:  "What?  I expect you to run this service.  How can you run this service if you don't know what Mr. X's calcium level is?"

The team got quite nervous in situations like that.  Training in medicine puts you directly in the line of fire or at least it used to.  These days commentary and affect like I witnessed that day might lead to some type of disciplinary procedure for the staff physician.  Something that could be passed down on credentialing forms and haunt a physician for the rest of his or her career.  A type of pseudoaccountability arranged by the bean counters essentially to manipulate physicians.  In this case, it was considered to be a learning experience and culturally appropriate.

In this case the intern in question seemed to recover.  Things went well for another few days.  And then he was gone.  The rumor was he was asked about another lab value, gave an answer that was slightly incorrect as in no physiological difference between the answers. He was fired for making up the answer.  Keep in mind that this incident occurred at a time when there were hundreds of lab values to track and the technology was at a primitive state relative to what is currently available.  The computers were slow and getting results took a lot longer.  Medical students, interns and residents had to write the labs down on cards using whatever shorthand they could devise.  In the process some data was memorized but not all or most of it.  But the difference here is that the integrity of the answer was called into question.  The assumption was that you either know the answer for sure  or you say you don't know.  There are no near misses.  The judgment is that you made something up and that is unacceptable.  In the years since, I have seen quite a few colleagues fall by the wayside as a result of similar incidents or what were considered to be errors in judgment by the senior faculty.

In recent times, I think there is a tendency to lump this behavior in the category of senior faculty being abusive toward physicians in training.  That certainly may be true, but it is also true that it draws a very clear line about what you need to be doing as a physician as opposed to what you may have done in your undergraduate major.  You can no longer make things up like you used to do in your philosophy and English literature classes.  You have to be brutally honest about what you know and what you don't know.  I don't think there is a physician alive who will not tell you that knowing this is one of the most critical aspects of training as a physician.  The ultimate test of whether you are patient centered is whether you will not try to protect yourself - but whether you can be brutally honest even in a situation that may put you at risk professionally.  Can you acknowledge mistakes, lapses in judgment and most importantly a lack of knowledge or expertise?  Patient safety depends on it.  That atmosphere also has the effect that you show up for work.  If you know that you are a target for any faculty who want to criticize you, you tend to want to know everything there is to know about the patients on your service.  In contrast to the events where the question does not get answered I have seen residents give tutorials on ventilator settings or pressure recordings by Swan-Ganz catheters.  They were motivated to some degree by knowing that teaching staff would be asking and their assessment depended on their answers.  

The reason for that introduction is that it frames the backdrop for a discussion from a financial thread with a very interesting title: Will Ebola Vanquish the MBAs Who Run Our Hospitals?  It is a title by a blogger and certainly eye-catching.  I have followed this blogger for a number of years and agree with a lot of what she has to say about the way financial services are managed in this country.  I have disagreed with her about some of her medical opinions, but this post is something that I can agree with.  I was recently e-mailed about my tendency to selectively find research that supports my opinions.  I consider this to be more opinion to support my opinion.  Research on how businesses manage medicine is as scant as research on management in general.  Business people tend to produce papers suggesting there are deficiencies and then say how they will correct those deficiencies.  There is really hardly any research to support business opinion.  The opinion in this case looks at a topic I frequently comment on - how can business people with no medical or scientific training manage physicians and medical facilities?  In my opinion they clearly can't but let's look at what is presented in this article.

The basis for the article is essentially opinion in the press and the opinion of a medical blogger.  The conflict-of-interest here that is usually glossed over is that any journalist, newspaper, or blogger wants the public reading their stuff.  It will be provocative or sensational.  A measured analysis is not typically seen.  For example the comparison of staff infection rates between the staff at Dallas Presbyterian Hospital (DPH) and Doctors Without Borders (DWB) in Liberia seems pointed, but the obvious question is whether the infections rates vary with experience.  For example did the DWB staff in the earliest stages of their involvement have infection rates as high as were portrayed in the DPH staff.  Can a direct comparison be done without that information?  The highlighted emergency department (ED) problems are similarly problematic.  If you pull up the Internet sites for the DPH system of care they are affiliated with a number of inpatient psychiatric units.  Is the wait time a reflection of a large pool of chronically mentally ill or poorly stabilised psychiatric patients being stuck in the ED?  If that is true it would still be consistent with some of the authors concern about the lack of public health concern and the fact that lower socioeconomic classes come face to face with the wealthy in such settings.  It is also an aspect of the mismanagement by rationing that is pervasive with systems of care managed by large businesses.

I have first hand experience with infection prevention in hospitals and attempt to stop widespread outbreaks from respiratory viruses.  Keep in mind that the Ebola virus is not an airborne virus.  All of the remarks in this paragraph are about airborne viruses especially Influenza virus.    For a number of years I was extremely disatissfied with the epidemics of respiratory viruses that swept through the staff where I was working.  Employer rules about paid time off only worsen the situation because the incentive is to work when you are sick to prevent loss of vacation days.  But the most frustrating part of the problem (apart from being sick 3-5 times a year) was that the employer had no real interest in doing anything that might reduce the risk of infections.  The intervention I suggested was just improving air flow in certain buildings.  The standard reply that you get is "wash your hands and cough into your sleeve."  Those are certainly common sense measures but as far as I could tell had no impact on the rate or severity of infections each year.  Hospital administrators everywhere seem to be in denial of the fact that airborne pathogens exist and washing your hands and coughing into your sleeve will not protect you against airborne pathogens.  I was also a member of two different Avian Influenza task forces.  At the time there was much uncertainty about a widespread epidemic that could not be contained.  We were setting up for the worst case scenario of thousands of people (both infected and not infected) coming into EDs and how to triage and treat people.  After years on these task forces it became apparent to me that nobody was really interested in planning for the prevention of mass casualties from an airborne virus.  There was no planning for any additional negative pressure airborne isolation rooms and no planning for any additional bed capacity in the event of a widespread epidemic.  There was planning for what to do with the expected bodies.  In the end it seemed that all of our hopes were pinned on a rapidly disseminated vaccine or antiviral medication.  The specifics of the antiviral medication were murky.  We were shown a picture of a large pallet of oseltamivir sitting in a warehouse somewhere.  From a business administrator's standpoint, planning to use imaginary resources from the government is always preferable to more functional planning because it is free.  My personal experience in this area from volunteer work on respiratory viruses is entirely consistent with the notion that health care businesses are not administered in a way that is consistent with public health needs in the case of infectious epidemics.

The Naked Capitalism article contains analysis from Roy Poses, MD of the Health Care Renewal Blog.  He looks at inconsistencies in the media and concludes that this is another case of health care leaders being untrustworthy.  That appears to be a central theme of his blog and he goes on to criticize them for being inconsistent, suppressing information from employees that may be critical to public health, and having an inflated sense of self importance.  These patterns are easily observed by physician employees of health care organizations.  For at least a decade after passage of The Health Insurance Portability and Accountability Act of 1996 (HIPAA) it was impossible to get necessary information from health care organizations, even in the case of needing to provide emergency care.  I would routinely request information and even send a HIPAA compliant release signed by the patient and I would get a blank form the other hospital saying that my patient had to sign their form and fax it back.  Hospital administrators were a big part of that process.  It is common for the clinical staff to be buffeted by the next big idea from their administrator.  That can range everywhere from high school style pep rallies that are supposed to improve employee morale to a new productivity system that is guaranteed to get even more work from physicians.  In every case, the administrator in charge could be making 2-5 times what the average physician makes for considerable less accountability, practically no "evidence based" methodologies, and no measurable productivity.  As pointed out in the article, public relations is much more of a factor in the CEO's reputation.  From the article:

" On Health Care Renewal we have been connecting the dots among severe problems with cost, quality and access on one hand, and huge problems with concentration and abuse of power, enabled by leadership of health care organizations that is ill-informed, incompetent, unsympathetic or hostile to health care professionals’ values, self-interested, conflicted, dishonest, or even corrupt and governance that fails to foster transparency, accountability, ethics and honesty." 

There are additional lessons from the decimation of mental health care in the United States, especially care delivered at tertiary care and community hospitals.  There is perhaps no better example of low to no value service that is the direct result of non-medical management.  There is no coordinated public health effort either improve the care of psychiatric disorders or specific high risk behaviors like suicide or homicide.  The standard approach is rationing of both care that would result in stabilization but also bed capacity that would alleviate congestion in emergency departments.  There should be no debate on cost, inpatient psychiatric care is without a doubt the low cost leader and is set to match reimbursement from a high turnover low quality model.  Psychiatric services in clinics and hospitals have a lot in common with what Dr. Poses observes on the administrative side of many health care organizations.

Responding to the question of  "Will Ebola Vanquish the MBAs Who Run Our Hospitals?" - my answer would be no.  It is always amazing to consider how so many people in business with so little talent can end up running things and making all of the money essentially through public relations, advertising and lobbying politicians.  There is no shortage of self proclaimed administrator-visionaries.  The author here should know that their power is consolidated around the same strategies that have worked for the financial services industry.  Managed care business strategies based on no science or input from physicians are now in the statutes of many states and in federal law.  They have successfully institutionalized business strategies designed to return profits to corporations as the rules that govern healthcare.  The pro-health care business lobby essentially gets what they want and the professional organizations are weak and ineffective, but continue to browbeat their members for contributions.  Administrators have a lock on running health care and demanding whatever accountability they demand from health care professionals while having no similar standards for themselves.

I can't think of a worse scenario for addressing potential public health problems whether that is an infectious epidemic or the continued mental health debacle.

George Dawson, MD, DFAPA

Supplementary 1:  Kaiser Family Foundation brief PowerPoint and Infographic on the current Ebola out break.

Supplementary 2:  I decided to add the above table comparing the accountability of physicians with business administrators.  Certainly there may be some things I have missed on the business administrator accountability so if I missed anything please let me know and I will include it.  From what I have observed, health organization and hospital CEOs are typically accountable to a Board of Directors that has very little physician or medical representation.  Often the Board is stacked with people who rubber stamp what the CEO wants to do.  Like the web site referred to in the above post there is often an aura that the CEO and the Board have visionary-like qualities that are based on public relations and advertising rather than any academic work or actual results.  I have never really seen an administrator who was a visionary or knew much about medicine - but  you can certainly read their proclamations about how medicine should be reformed on a daily basis in many places on the Internet.  The usual argument for all of the physician accountability is that it is a privilege to practice medicine and therefore regulation of physicians needs to reduce the privacy rights of physicians and subject them to much closer regulation than other professionals.  Why wouldn't that approach apply to the people who actually determine whether a patient gets health care, medications or a specific benefit?  Why wouldn't that same logic apply to the people who really run the health care system?

Wednesday, October 15, 2014

University of Wisconsin 2nd Annual Update - Day 2

The second day of the conference was actually a half day that was as interesting as day 1.  The first speaker was Kenneth E. Towbin on Chronic Irritability and Pediatric Bipolar Disorder.  Dr. Towbin pointed out that all of the research discussed by him at the meeting was funded by the NIMH Intramural Research Program or the American taxpayers.  He briefly mentioned the advantages and disadvantages of working under those conditions including no usual conflicts of interest and working in an ivory tower with possible ascertainment bias.  The main focus of his discussion was to make a few points about the concept of bipolar disorder and how the overdiagnosis of this disorder came about.  The first point was that bipolar disorder is an episodic illness.  The word I like to use is phasic.  The second point sounds obvious to psychiatrists and that is that in order to make a diagnosis of bipolar disorder the patient has to have had an episode of mania or hypomania.

I am going to digress here a bit on my own before continuing the review of Dr. Towbin's work.  Much of what I do these days is correcting incorrect diagnoses of bipolar disorder.  When I try to reconstruct what happened patients will invariably tell me that they were given an "assessment" and told that they tested positive for bipolar disorder.  The assessment typically consists of a brief interview and then a battery of checklists and psychological tests.  Many are surprised when I tell them that the diagnosis really doesn't depend on any of those things.  It depends on whether or not they have had an episode of mania or hypomania and then I define those syndromes for them.  We try to reconstruct their history of mood disorders and whether or not they have ever had such an episode.   I also emphasize that these episodes have to occur when they are not using excessive amounts of alcohol or other intoxicants.  I ask them about the time before they developed a substance use problem and during their longest periods of sobriety.  In this day of overdiagnosis of Attention Deficit-Hyperactivity Disorder (ADHD) it is not uncommon to hear that a person who has developed a substance use problem using all of their Adderall in the first week or two.   When that is gone  they switch to alcohol for the second half of the month.  That combination can result in what appears to be a manic episode during the first week or two of the month followed by a 2-3 week depression.  That sequence of stimulant intoxication followed by stimulant withdrawal/alcohol intoxication followed by sustained alcohol intoxication is not bipolar disorder.

Dr. Towbin went on to give his very interesting take on how some mistakes can be made from reading diagnostic criteria.  He focused initially on how there could be ambiguity in the DSM-IV-TR.  For example under the "A-Criteria" - how is the requirement of a one week episode of elevated mood determined?  Does it have to be every day or every hour?  Could it last for a short a period of time as an hour?  Under the "B-Criteria" - could some symptoms antedate mood symptoms and what does "present to a significant degree" mean?  I was familiar with Angst's work on following patients with various durations of mania and what the outcomes could be and had since incorporated a shorter period of time into my evaluations of mania.  The DSM-5 criteria sought to clear up these areas by stating that the mood symptoms had to be present most of the day and nearly every day and the symptoms had to represent a noticeable change from usual behavior.   After these discussions of the nature and importance of manic episodes he went on to look at some epidemiological data on the increasing rates of bipolar disorder in children (1, 2).  In the study by Moreno, et al the authors demonstrated a significant increase in office visits by adults and children.  Between the years of 1994 and 2002 the rates of visits increased 60% for adults and 4,000% for children, but the rates from that graphic increased from 0.01-0.4% in children and 0.3 to 0.5% in adults.  Between 1996 and 2004, the number of inpatient discharges with a principle diagnosis of bipolar disorder increased 296.4% in adolescents and 438.6% in children.

Towbin's explanation for the increase in bipolar disorder diagnoses in children was that a cultural change was advanced by two research groups.  That cultural change was operationalized by saying that episodes of illness were not required and the diagnosis could be applied to children with chronic illness.   That led to the idea that bipolar disorder in children is not the same as bipolar disorder in adults and that chronic irritability was synonymous with bipolar disorder.  Or as he put it another way: "If you were really angry you must have bipolar disorder."  The importance of bipolar disorder as an episodic illness was also emphasized in the area of "double counting symptoms."  As an example, could the psychomotor agitation and flight of ideas of bipolar disorder be the same thing as severe hyperactivity or distractibility of ADHD?  Only if bipolar disorder was not an episodic illness.
Dr. Towbin proceeded to discuss how the concept of Severe Mood Dysregualtion (SMD) was developed at the NIMH as an additional clinical phenotype that could be compared to bipolar disorder.  SMD was defined as chronic irritability, ADHD-like symptoms and significant impairment.  At about the same time he went on the one of my favorite topics - irritability.  I like it because it is used as a descriptor in many DSM diagnoses but never well defined.  Many people are surprised that it is listed as a symptoms in Generalized Anxiety Disorder (and in the criteria for 6 other DSM diagnoses and in the text for an additional 3 DSM disorders.)  He defined a two component model for irritability including a background of a grumpy, annoyed and irritable mood and a phasic component of briefer flashes of anger or explosive episodes.  That allowed for a clearer definition of SMD and the subsequents development of Disruptive Mood Dysregulation Disorder DMDD) diagnostic criteria.  He reviewed the evidence from longitudinal studies, family history studies and pathophysiology that SMD/DMDD is not the same as bipolar disorder.  Followed for a long enough period of time this population tends to develop depressions rather than bipolar disorder and have families with histories of bipolar disorder.  From a recent study by Sparks that he referenced: "Parental bipolar disorder increase the risk for multiple categories of childhood psychopathology and DMDD is no more on the bipolar spectrum than anxiety disorders, MDD, or ADHD." He went on to discuss treatment approaches to this population emphasizing the significant degree of disability the is usually not discussed in non-technical publications about this problem.

The final speaker of the day was Zachary N. Stowe, MD.  His presentation was: Treatment of Mood Disorders in Pregnancy and Lactation: Where Are We Now?  He made two observations at the outset that probably captured the imagination of at least some of the crowd.  The first was that any psychiatrist who specialized in the neuropsychiatric disorders of pregnancy would be unchallenged in any community they decided to practice. The second was that every psychiatrist treating women should treat all women of child-bearing age as though were pregnant and therefore needed clear conversations about whether they are using contraception and what the permutations might be with respect to prescribed psychiatric medications.  The method of birth control should be documented.  In terms of safe use of medications in pregnancy he made the point that is is all based on post marketing surveillance and there is no safety data for using 2 medications at a time.

He reviewed the frequent scenario that clinicians face when a patient who is being treated becomes pregnant.  He used an excellent graphic showing how pharmacokinetics and the timing of human development combine to virtually assure that the fetus will probably be exposed at some critical stage of organogenesis and how that factors into the decision to continue, discontinue, or change pharmacotherapy.  He showed survival curve data from both treated and untreated major depression and bipolar disorder on the proportion of women remaining euthymic at and several weeks following delivery.  As expected the rates of recurrence of the mood disorders was high and significantly higher for bipolar disorder.

When discussing the risks of medication he mentioned the current FDA Pregnancy Categories and the fact that there will be a new system that looks at more of the clinical aspects of making these decisions.   The old system will remain in place for existing ratings meaning that for the forseeable future there will be two FDA systems looking at medication safety in pregnancy.  He looked at a number of maternal and neonatal outcome variables for pregnancies associated with maternal depression and maternal antidepressant use.  There was a significant overlap and he suggested that a psychiatric illness diathesis and all that encompasses in terms of cormorbid medical illnesses and activation of the maternal and fetal HPA axis was a possible explanation.  In other words there  would be non-optimal outcomes whether the depression is treated or not.  He went on to discuss detailed basic science research in this area as well as fairly detailed treatment recommendations.  From a clinical standpoint, he pointed out that psychiatrists are more likely to discontinue antidepressants in pregnant women than OB-GYN physicians and attributed that to the American College of Obstetricians and Gynecologists treatment guidelines for depression in pregnancy.

Dr. Stowe's presentation covered all modalities of treatment including electroconvulsive therapy, medications, psychotherapy and exercise.  He was a participant in a workshop I attended on treating depression with exercise.  I think the single most important fact that he discussed in terms of medication was the need to avoid valproate and consider it to be the last drug used in women of child bearing age because of its effects on the fetus and subsequent development of the child.  I recommend that any psychiatrist who has the opportunity to see Dr. Stowe and who treats women of childbearing age take advantage of that opportunity.

That ends my brief review of the UW conference this year in Madison.  I felt fortunate to have been actively involved in all of the clinical work that these clinicians and researchers discussed over a day and a half.  I thought of all of the patients I had seen who could have benefitted from seeing this basic and clinical science applied.  As I listened to the translational aspects of Dr. Stowe's work, I tried to think of all the women I had treated who developed a severe post-partum affective psychosis at some point in their lives and never recovered from that.  I appreciated the quality of a conference that puts all of that information out there and tries to bring everyone up to the same speed as the top researcher-clinicians out there.

If you think this approach might interest you - mark your calendar for next October 23 and 24 and I hope to see you there.  In the two years that I have attended, Art Walaszek, MD and Ned Kalin, MD have an excellent method of picking presenters who can cover both the clinical and basic science of important disorders and treatment modalities that psychiatrists need to be aware of.  That information is presented well and there is ample time for discussion.

George Dawson, MD, DFAPA

1: Moreno C, Laje G, Blanco C, Jiang H, Schmidt AB, Olfson M. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch Gen Psychiatry. 2007 Sep;64(9):1032-9. PubMed PMID: 17768268.

2: Blader JC, Carlson GA. Increased rates of bipolar disorder diagnoses among U.S. child, adolescent, and adult inpatients, 1996-2004. Biol Psychiatry. 2007 Jul 15;62(2):107-14. Epub 2007 Feb 16. PubMed PMID: 17306773.

Monday, October 13, 2014

University of Wisconsin 2nd Annual Update

I was in Madison Wisconsin for the Second Annual University of Wisconsin Clinical Update.  I reviewed the first conference last year.  For anyone unfamiliar with the conference it started last year as a replacement for the long running conference run by John Greist, MD and James “Jeff” Jefferson, MD.  They were acknowledged again this year for their contributions to psychiatric education.   This is a very good conference because it builds on that tradition.  The actual venue is the Monona Terrace Convention Center on the shore of Lake Monona.  It is an excellent modern facility with only one drawback - they charge for high speed wireless access.  I talked with many psychiatrists there who had attended the previous conferences for a long time.  They bring in speakers who are some of the top experts in their fields for in depth presentations and there is also a strong department at Wisconsin headed by Ned Kalin, MD.  The conference wraps up in in a day and a half and that seems like a very good length for working psychiatrists.  Combine that with very accessible speakers and an excellent course syllabus and it has what I consider to be the elements of a good educational experience.  The other bonus is that I have never really seen an unbalanced presentation at this conference.  The overarching message is that there are a number of interventions, that treatment is successful, and that there is a scientific basis for what psychiatrists do.

I thought I would make a few comments on day 1 and then move on to day 2.

The first lecture was given by Maria A. Oquendo, MD on the Neurobiology, Assessment, and Treatment of Suicidal Behavior.  Aleman and Denys have called for the investigation of suicide as a special problem apart from any particular diagnosis.  She began with a review of the epidemiology of suicide, including the fact that 90-95% of suicides have an psychiatric disorder.  She also discussed the converse of that statement - the vast majority of patients with psychiatric disorders never attempt suicide.  That statement is usually not discussed.  It is a parallel argument to violence and aggression in psychiatric disorders.  It has implications for any care based on dangerousness (threat of aggression or suicide).  She presented an interesting stress diathesis model of suicidal behavior that takes into account clinical features (impulsivity, cognitive inflexibility,  substance use,  family history, poor social support) and neurobiological features (low serotonin, decreased noradrenergic (NA) neurotransmission, inflammatory markers).  Her model links norepinephrine neurotransmission with pessimism.   She cited evidence that included a slide of CRH innervation of NA neurons and behavioral models that lead to NA depletion in animals.   She reviewed some of the evidence of inflammatory signaling related to childhood adversity, the mechanism of interferon-alpha induced depression and markers of inflammation in suicide attempters versus controls (increased interleukin- 6 (IL-6), tumor necrosis factor - alpha (TNF-alpha), elevated microglial cells, increased IL-4 in women, and increased IL-13 in men.  The tentative conclusion is that suicide occurs in the context of a stress response or at least it appears to have the same neurobiology of a stress response.   She concluded with a discussion of public health approaches to preventing suicide.  She had no specific recommendations for how psychiatry fits into that response apart from presenting data that increased antidepressant prescriptions led to decreased suicide rates in Sweden, Hungary, Japan, and Slovenia.   She also discussed specific psychotherapeutic interventions for suicide by name and presented a study of cognitive behavioral therapy that led to a 50% reduction in suicide attempts.   Dr. Oquendo also provided an excellent contrast in how the results of observational studies, meta-analyses, and double blind placebo controlled studies can differ and what biases may be in effect.  In the case of lithium preventing suicidal behavior, most clinicians are aware of the fact that only lithium and clozapine are consider medications that prevent suicide.  In the case of lithium, it turns out that data is from observational studies and meta-analyses but not double blind placebo controlled trials.  The two double blind studies do not suggest that lithium is more effective in preventing suicides than other agents.  She suggested one bias may be a tendency of clinicians to use lithium in people who can use it more safely and that led to fewer suicide attempts.          

I found the presentation on suicide and suicide assessment very interesting.  It is such a broad topic that a single lecture has to pick a focus.  The presentations on suicide that I have seen tend to focus on trying to figure out which people attempt suicide and interventions in those populations.    People with psychosis and suicidal ideation – a common clinical scenario for psychiatrists are generally left out.  It would definitely complicate the presentation at a couple of levels.  There is the issue of what happens to the usual risk factor analysis, especially in the case of subtle forms of psychosis.  Factors that are typically seen as reliable (deterrents to suicide, prevention plans) can be thrown out in that situation since the patient has had a marked change in their conscious state.  That is true whether or not the patient is clinically interviewed or given a structured interview like the CCRS.   In the case of psychotic individuals paranoia is also a risk factor for suicidal behavior.  The paranoia is focused on a particular situation where the individual believes that he or she will be tortured or killed by someone.  They develop a plan to kill themselves rapidly using a highly lethal method before that can happen.   A common scenario is to have a knife or handgun on the nightstand just in case it becomes necessary.  In both of these treatment situations, the preferred course of treatment is to address both the depression and psychosis at the same time.   Past studies of these populations also suggest very high levels of hypothlamic-pituitary-adrenal (HPA) axis activation, consistent with Dr. Quendo's model.

Roger McIntyre, MD followed with Practical Considerations in the Successful Treatment of Bipolar Depression.  There seems to be fairly widespread confusion about the diagnosis of bipolar disorder.  I think it is common for consulting and subspecialty psychiatrists to reverse the diagnosis of bipolar disorder more often than they make new diagnosis.  Dr. McIntyre made that point but said that misdiagnosis is still a problem even in an era of overdiagnosis.   He took the assessment up a notch to discuss the utility and limitations of the diagnostic issues of bipolar qualifiers in DSM-5 ( mixed features, anxious distress) and what they imply for diagnosis and treatment.  He also emphasized the need for time to do an assessment.  He appreciates the fact that primary care physicians may have as little as 6 minutes to make a mood disorder diagnosis but said that even in his specialty clinic he may not know the diagnosis of 25% of the patient after doing a lengthy assessment.  He made this point to illustrate that in many patients a single cross sectional view of symptoms in a clinic appointment is insufficient to make the correct diagnosis.

He presented an excellent graphic showing the DSM-5 continuum from manic to manic with mixed features to depressed with mixed features to depressed.  He also spent a fair amount of time discussing the treatment of comorbid anxiety as a significant morbidity in bipolar disorder.  He presented interesting data on how comorbid medical and psychiatric conditions in bipolar disorder were the rule rather than the exceptions.   His main focus was on metabolic syndrome, obesity, and migraine headaches.  He presented very good graphics on mechanisms associated with these comorbidities.  He made the point that the metabolic abnormalities (much like studies done in patient with schizophrenia who had never been treated with medications) were associated with a number of social, metabolic, and environmental factors.  He suggested that the obesity/major depression and obesity/bipolar disorder phenotypes carried specific risks including poor cognitive performance, anxiety symptoms, and in the case of depression a possible higher suicide risk.   He cited estimates of metabolic syndrome ranging form 20-66% in populations with bipolar disorder compared to a general population estimate of 23.7% from the NHANES III study.  He presented interesting data on the correlation between cognitive impairment in obese and overweight bipolar patients that can be demonstrated in first episode manic patients (obese versus non-obese).  At the molecular level it has been demonstrated that there is a gradient of inflammatory markers between obese and non obese bipolar patients.   He has a published paper that looks at the relationship between treatment response in depression and body weight.  Although he did not speculate on an exact mechanism he suggested there were altered brain systems involved in cognition in many of these patients.

The section of Dr. MacIntyre's lecture included an interesting graphic that had all FDA and EMA (European Medicines Agency) approved medications for bipolar-manic, bipolar depressed, and maintenance therapy.  Both agencies have approved quetiapine for bipolar and only the FDA has approved lurasidone and olanzapine-fluoxetine combination (OFC).  The number of medications not approved in all columns is about the same (4 for EMA and 3 for FDA).  He presented number needed to treat (NNT) and number needed to harm (NNH) analyses for OFC, quetiapine, and lurasidone and in that analysis lurasidone looked like the superior medication but that analysis is for specific side effects.  The NNT was nearly identical for all medications.  In terms of overall treatment he was in general agreement with the Florida Medicaid Drug Therapy management Algorithm.   One of the very interesting points he made during his presentation was that treating and preventing recurrent manic  episodes may reduce risk for Alzheimer's dementia but that is potentially confounded by the effect of lithium on GSK-3-induced tau phosphorylation.         

Lithium Pearls (From several lectures)
1.  The claim that lithium is one of two medications that can prevent suicide is based on observational studies and meta-analyses.  There have been two double blind studies looking at this issue and they have both been negative.
2.  Experts continue to use lithium and consider it to be one of the major treatments for bipolar disorder.  Lithium may provide more benefit to manic prone patients with long periods of stability and a positive family history.
3.  Once a day dosing was recommended.
4.  Lithium can be used in pregnancy given several specific precautions and informed consent issues; including precautions are the time of delivery to prevent elevated lithium levels in the newborn.
5.  Lithium may decrease the risk of Alzheimer’s Disease and minimal cognitive impairment.
After afternoon breakout sessions on various topics, the final presentation was by Ned Kalin, MD on the Neurobiology of Depression.  As a point of disclosure I know Dr. Kalin and was his first fellow at the University of Wisconsin back in 1984 and I completed my residency there.  He is a model of the clinical researcher who has seen patients his entire career and also been involved in basic science research.  There were several other department members at Wisconsin engaged in the same balance of clinical and scientific activities.   I learned that he was also President Elect of the Society of Biological Psychiatry.  The UW has always been active in primate research and Dr. Kalin discussed some important ethical and scientific issues about basic science research in non-human primates including the reason for primate research and the changes in standards and research settings over the years.  He has broadened his research over the years to include how depression and anxiety start in childhood and adolescence.   He posted an interesting graphic on deaths worldwide due to violence that suggested suicide was the top cause, followed by homicide and then warfare.  It was based on World Health Organization (WHO) data.  He showed experimental data on conscious regulation of the amygdala.  These interesting studies show that activity in the amygdala can be modulated by cognitive activity that either enhances of decreases the response to the feared stimulus.  The ventromedial prefrontal cortex (vmPFC) and orbitofrontal cortex (OFC) are critical associated areas with activity correlating inversely with activity in the amygdala (high vmPFC and OFC activity correlate with low activity in the amygdala).   Preliminary data suggests that depressed patients fail to suppress activity in the amygdala with vmPFC and OFC activity.  A similar change occurs in the ventral striatum when depressed individuals attempt to enhance their positive affect over the course of an imaging session.  Controls show a significant increase in left nucleus accumbens activity (LNAcc).

Dr. Kalin reviewed the genetics and environmental factors in depression using a graphic that cited 3 of Kendler's papers.  He reviewed the progression of hypotheses ranging from monoamine depletion to altered serotonin neurotransmission to serotonin alteration hypothesis to  stress diathesis to neurotoxins to inflammatory/cytokine theories.  One of the possibilities he discussed was a theory that at least some developmentally based depressions are based on frontal cortical-amygdala substrates that result in increased activity in the amygdala and associated neuroplasticity mechanisms that also lead to increased vulnerability.   Cognitive therapy for depression may strengthen the ability of the frontal cortex to regulate the amygdala.  One of his areas of intensive investigation has bee the HPA axis and its effect in depression.  He reviewed the important roles of CRF both as an endocrine modulator and a neurotransmitter.   He used a Vonnegut quote from Breakfast of Champions as a quick review of HPA axis physiology.  For anyone who had read the book (and forgotten some physiology) it was an interesting reference.   In the last quarter of the lecture he reviewed the issue of stress in separated infants, maternal stress, and adults in human and non-human primates.  The focus was primarily on neuroanatomy, neuropathology, neuroendocrinology and possible treatments that target these systems.  Earlier in his discussion he also posted a graphic on translational neuroscience and how neuroscience findings need to be able to correlate at the clinical level.  A detailed discussion of that approach is available in this article that is available online at no cost.              

The first day in Madison went as well as expected.  Lectures with very high quality content by researcher-clinicians who actually see patients and investigate clinically relevant topics.  Psychiatry taught, researched, thought about, and practiced the way it should be.

George Dawson, MD, DFAPA

1: Oquendo MA, Galfalvy HC, Currier D, Grunebaum MF, Sher L, Sullivan GM, Burke AK, Harkavy-Friedman J, Sublette ME, Parsey RV, Mann JJ. Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior. Am J Psychiatry. 2011 Oct;168(10):1050-6. doi: 10.1176/appi.ajp.2011.11010163. Epub 2011 Jul 18. Erratum in: Am J Psychiatry. 2012 Feb;169(2):223. PubMed PMID: 21768611

2: Lauterbach E, Felber W, Müller-Oerlinghausen B, Ahrens B, Bronisch T, Meyer T, Kilb B, Lewitzka U, Hawellek B, Quante A, Richter K, Broocks A, Hohagen F. Adjunctive lithium treatment in the prevention of suicidal behaviour in depressive disorders: a randomised, placebo-controlled, 1-year trial. Acta Psychiatr Scand. 2008 Dec;118(6):469-79. doi: 10.1111/j.1600-0447.2008.01266.x.

3: Fox AS, Kalin NH. A Translational Neuroscience Approach to Understanding the Development of Social Anxiety Disorder and Its Pathophysiology. Am J Psychiatry. 2014 Aug 26. doi: 10.1176/appi.ajp.2014.14040449. [Epub ahead of print] PubMed PMID: 25157566.

4: McIntyre RS, Rosenbluth M, Ramasubbu R, Bond DJ, Taylor VH, Beaulieu S, Schaffer A; Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force. Managing medical and psychiatric comorbidity in individuals with major depressive disorder and bipolar disorder. Ann Clin Psychiatry. 2012 May;24(2):163-9. Review. PubMed PMID: 22563572.

Supplementary 1: I thought it was very interesting that we are still talking about lithium as a very effective medication for psychiatric disorders int he same city that hosted the Lithium Information Center cofounded by Greist and Jefferson and the same location where the Lithium Encyclopedia for Clinical Practice was published.