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.


  1. Towbin is right on.

    People like Angst use circular arguments in order to expand the diagnosis of bipolar disorder: Several of us had a letter published in the Archives of General Psychiatry calling them out on this, which is described in the post.

    They're also good at saying that a chaotic home environment of kids is not a factor in their distractability on the basis of maybe one question to the parents. In this case WNL does not stand for "within normal limits," but for "we never looked."

  2. The Angst reference was to his long term studies on duration of manic episodes and which duration is predictive of actual bipolar disorder. The idea of overdiagnosis of bipolar disorder has always puzzled me because it seems so straightforward. But then I have always seen it as an episodic disorder that required a manic episode. For adult psychiatrists an equally significant problem is when a person with true bipolar disorder suddenly ends up with a diagnosis of schizoaffective disorder because they were never adequately stabilized. They are easy to find if you actually read and study old records because they have early clear descriptions of bipolar disorder.

    1. Absolutely! True mania is not subtle at all.

  3. Excellent article Drs. Dawson and Allen. Bipolar, like autism once was, used to be very UNSUBTLE and reliably diagnosed. But there's no money in that.