My First Flu Shot

I got my very first flu shot on 12/3/2013.  Up until now I have depended on my coworkers being vaccinated and protecting me against the virus.  Very recently I have had Tamiflu and at the times I have used it thought that it worked very well.  I have asked repeatedly about getting the shot, including the Infectious Disease consultants who promoted the mass immunization of my fellow employees.  Over the years I have asked about 5 of them this question and they all said the same thing: "You can never take this flu vaccine."  My history was: "In 1975 I received two doses of anti-rabies duck embryo vaccine and had two episodes of anaphylaxis".  I was very interested in the new vaccine (Flucelvax) for people with egg allergies and when I asked about it, my primary care doc was initially enthusiastic, but then told me I had to be evaluated by Allergy and Immunology in order to get it.  That lead to a comprehensive evaluation that was nearly three hours long.

After the check in and doing some asthma tests, I met the Allergist.  He was about my age and the first thing I noticed was that he was gathering a history in nearly the same way I do.  It was detailed and comprehensive.  Not just the buzz words but what actually happened right down to what that duck embryo vaccine looked like in the syringe.  It was oily and it had particles in it.  Even in those days I was skeptical of the idea that all Peace Corps volunteers going into a specific country needed to take it.  There were about 50 of us and in the two years of service, I don't recall hearing that anyone was bitten by an animal.  The first time I got it, I broke out in hives and had a rash.  My friends took me down to a local Kenyan hospital where they gave me Polaramine (dexchlorpheniramine) and epinephrine.  When I got the second injection, I got intense abdominal cramping, hives, swelling of the face and lips, wheezing and lightheadedness.  At that  point they gave me Benadryl (diphenhydramine) and epinephrine.  Even though I can recall the antihistamine they were using in Kenya at the time, I can't recall why they gave me the second shot.   The Allergist wanted all of these details and more, like when was the first time anything like this happened.

That was 50 years ago.  The anchor point was the JFK assassination.  The day before his funeral I shot myself in the left eye with a BB gun and developed a hyphema.  I was hospitalized for a week and the hemorrhaging resolved completely.  In the follow up, I was in the ophthalmologist's office next to a fish tank.  My face started to swell of to the point that my eyes were swollen shut and my lips were extended.  I developed hives over much of my body.  I started to wheeze.  They moved me into a different room and talked with my mother who told me later that the diagnosis was "psychosomatic reaction".   Apparently the stress of not losing an eye or my vision was felt to be a more likely etiology than a moldy fish tank.  For the next 10 years or so, I start to wheeze when mowing the lawn.  I would get up in the middle of the night with hives or wheezing and drank Diet Pepsi until it went away and I could go back to sleep.  At some point one of the primary care docs in town gave me an epinephrine based inhaler.   I didn't see my first real allergist until I was about 25, after the Peace Corps and working at my first job cloning evergreen trees.

The skin testing began at that point.  96 patch tests up and down my back, all of them very positive.  I was given a long list of what to avoid and it was basically unavoidable.  I began a long series of immunotherapy injections, but gave up when they did not seem to do anything.  I remembered taking TheoDur the entire time I was in medical school and doing a rotation in Allergy and Immunology.  I gave a presentation about what was known about anaphylaxis at the time and at the end, one of the allergists seriously questioned me about why I was going into psychiatry rather than internal medicine.  During residency, I took my first course of prednisone for a flare up of asthma after a viral infection.  Since then, it has been random episodes of spontaneous anaphylaxis, corticosteroid inhalers and trying to minimize my exposure to them when possible, and using antihistamines and an Epi-Pen when the episodes of anaphylaxis seem particularly bad (that is infrequent).  The Allergist recorded this 50 year history of mostly inadequate treatment.

At the same time, I was marking where I would be in an interview with a person who had lifelong depression and anxiety.  Attempting to reconstruct the episodes of mood disorder and what the symptoms were.  Attempting to correlate it with major life events.  Attempting to determine in retrospect the exact nature of the symptoms and likely etiologies at the time.  Asking myself if the treatments received were appropriate or what it suggested.  Thinking about the resilience or vulnerabilities of the person I was talking with.  It is the same process I use in making diagnoses and treatment plans.  Were there differences?  Of course and the most noticeable were the objective measures for assessing asthma.  I did the usual assessments of FEV1.0 before and after bronchodilators.  There was also a new assessment of alveolar nitric oxide (NO) as a measure of asthma  control.  It would be extremely useful to have tests like that to objectively measure the distress, anxiety, or depression levels of the person sitting in front of me, especially if it involved something as simple as blowing into a tube.

But the most interesting part was that in the end, the Allergist addressed the question about whether I could take an egg cultured influenza vaccine by carefully synthesizing the data and correctly answering the question.  He did not need a test of any sort to answer the question.  He took a meticulous 50 year history of a guy with life-long allergies including asthma and anaphylaxis and correctly concluded that I could be given the shot, even though all of the experts with the same level of training had come to the opposite conclusion.  I got the shot, sat in the clinic for 30 minutes.  The information sheet said that delayed reactions for "up to several hours" could occur.  He told me that would not happen and I went home.  That was almost exactly 24 hours ago.

The lesson here is one that I have seen time and time again in the field of medicine.  The information content in the field is vast.  There may be only a certain physician or specialty capable of answering that question.  There is no better example than me getting a flu shot, but it also happens daily in the people I see who have had psychiatric disorders for the same length of time or less than I have been dealing with allergies and asthma.  No two people with asthma or depression are alike.  Meticulous history taking and pattern matching can get to the correct answer.  Suggestions that we can treat a population of people all in the same way will not.

People are biologically complex and as physicians we should celebrate that.  That also involves getting them to the person who can correctly answer their questions.

George Dawson, MD, DFAPA

The Selling of Medical Marijuana

I have been thinking about how to approach this topic for a while.  My experience is not the experience of most people because as a psychiatrist I am seeing some of the worst possible outcomes.  That usually involves psychotic symptoms, depression, severe anxiety and panic, paranoia or some combination of all of these symptoms.  I have seen a much larger group of people who stopped on their own, usually after getting paranoid or experiencing a panic attack.  A lot of people cannot stop smoking even when they have a clear medical problem.  In some cases they are using marijuana or some cannabinoid product for a specific medical problem despite the fact that they are not getting relief and I would not expect them to.  These folks are typically heavy smokers (blunts, spliffs, vaporizers) but like all pharmacologically active compounds the dose response curve is highly variable.  

The  epidemiology of major symptoms caused by cannabis use has become a lot clearer in the past 10 years.  Thirty years ago there was an isolated study showing that army conscripts who were marijuana smokers were more likely to develop schizophrenia.  There was also a prominent researcher at the time suggesting that populations where there were high levels of cannabis use did not have higher rates of psychosis.  But those populations did not have high quality epidemiological data.  The latest studies show significant increases in the likelihood of schizophrenia and mood disorders.  I think that this probably happens in a minority of people and probably those consuming the most THC.  There is a lot of discussion about the differences in THC content of marijuana in the 1970s relative to what it is now, but not much reliable data to back that up.  Since THC is a pharmacologically active molecule with known pharmacokinetic properties it is always a question of dose as well as potency.  Multiple doses will eventually get you to the same levels of fewer doses of a more potent product.  he need to avoid positive urine toxicologies for THC also drives the market in synthetic cannabinoids, since the word on the street is that taking these drugs does not result in a positive toxicology screen and jeopardize employment.

A recent public opinion poll shows (click  to enlarge).  The recent trend to legalize comes in the context of an increasing trend about using marijuana and other controlled substances for legitimate medical purposes and media portrayals of marijuana as a source of employment, entertainment, and alternative medicine.

There is not the same level of skepticism about marijuana as there is about psychiatric medications.  In that case, the drugs are approved as safe and efficacious by regulatory bodies.  There is no evidence that they cause problems at anywhere near the level of marijuana and yet the latter is generally given a bye in the media.  Incredibly, many states get around the legalization of a scheduled drug by making it a "medically necessary" substance.  In spite of the fact that cannabis has been around for over 850 years and tens of thousands newer medications were invented and used successfully, the myth that cannabinoids are necessary as a medication has been promulgated in an apparent effort to increase the legalization of this substance.  The Obama administration has taken a public stand on the medical marijuana issue saying that the state statutes stand, but that they will engage in a selective prosecution that targets organized and violent crime, especially if that crime involves children or increased access to firearms.

I think that medical marijuana is generally a concept that has little to do with medicine and more to do with the legalization of marijuana.  It would become much more obvious if there were exposes in the press about how prescriptions for medical marijuana actually work.  What has to be said in the interview to get the prescriptions and what are the incentives of these prescribers?  We have had a fairly constant barrage of criticism of psychiatrists prescribing non-addicting drugs to patients for legitimate FDA approved indications that are in aggregate safer than cannabinoids.  Where are the questions about an industry that is selling a potentially addictive drug that has no clear medical indication and the potential conflict of interest of the prescribers?  I certainly have no problem continuing to advise all my patients with, anxiety, mood, addictive, and psychotic disorders that they need to not use marijuana at all, despite the fact that they are getting advice that marijuana is good for anxiety, depression, and insomnia.  I also have no problem telling anyone who might want a medical marijuana prescription that medical marijuana is a political term that has nothing to do with the practice of medicine and as such - I am not a "prescriber".

The other physician dimension to this issue is overprescribing.  The current epidemic of prescription opioid use and resulting accidental overdose deaths is a good example.  Unlike marijuana, the opioids have clear indications for use and contraindications.  In aggregate, marijuana probably has a wider safety margin, but the prescribing dynamic is similar to opioids and antibiotics.  The physician is confronted with a highly motivated patient who wants to leave the office with a prescription and physicians have have varying levels of motivation and skill to deny a wanted but unnecessary prescription.

I have no problem with any state declaring marijuana or any cannabinoids legal for its residents to line up and purchase.  Although marijuana promoters always give the message that it is safer than alcohol, it has the same general parameters  of use and no real medical indication.  I do have a problem with involving medicine in an experiment to legitimize it for just about anything.  I also think that physicians should know better.  We ran similar experiments for drugs with clear medical indications like opioids in the past century and they did not turn out well.

George Dawson, MD, DFAPA

American Society of Addiction Medicine (ASAM):  ASAM Medical Marijuana Task Force White Paper.

Joseph Lee, MD on Marijuana Legalization and the Impact on Children and Adolescents.

Dr. Oz addendum:

An example about the type of information the public gets from the media can't get any better than this Dr. Oz episode "Is Weed Addictive?" on December 4, 2913.  The full details are not really provided at this time.  I saw a debate and one of the participants was Pamela Riggs, MD who provided standard information on the addictive properties of marijuana.

Dr. Oz posts additional comments on his blog and seems to confuse the issues of addiction, legalization, and medical use.  After talking how it is going to be widely available he concludes:

"As the trend towards legalizing this drug continues, we need to be aware of its risks and teach our children its proper place, which is in the pharmacy, not in the kitchen cabinet and certainly not in the school locker."

So it will be more widely legalized as a pharmaceutical that people will use that way?

I will post additional details of this broadcast as they become available.

Lessons From Google on How To Manage Physicians

This month's Harvard Business Review has an interesting article on managing technical professionals entitled:  "How Google Sold Its Engineers on Management."  One of the secondary goals of this blog is to point out how people who manage physicians are not only technically inept but in many cases openly hostile to the physicians they manage.  That is largely because the entire system is based on artificial productivity measures and practically all of the management is focused on how to get more artificial productivity out of physicians.  A classic example of this kind of management focuses on how many deeply discounted patient visits are seen per day.  Other tasks like chart checks, telephone calls, paperwork of various kinds, and the tremendous burden of managing the electronic health record and all that involves are not counted as productivity of any sort.  Physicians are basically expected to do all of that plus teaching and lecturing on their own time.  In one system where I worked you were given points for being a good citizen and eligible for some trivial reimbursement if it was apparent that you were doing more than cranking out RVUs (the standardized measure of productivity).

This whole system of management is archaic in that it is a system that was set up to manage production workers and not knowledge workers with technical expertise.  Physician managers seem oblivious to the fact that the product of their organization rests solely in the expertise of their doctors.  A healthcare organization will only be that good and it is in the interest of that organization to retain and develop the careers of the best physicians they can find.  That is not the prevailing way that employed physicians are managed.  In fact, physicians are micromanaged and their decisions are routinely second guessed.  In the worst case scenario, if the physician disagrees with the financially based decisions of their managers they can be fired or politically scapegoated for not being a team player.  Some physicians may be subjected to several of these confrontations per day often over trivial cost savings.  In psychiatry for example, the arguments often arise over length of stay considerations where there is a set reimbursement for a hospital stay and the manager wants the person out sooner so the hospital can make more money.  The patient care goals of the physician based on their technical expertise and the financial goals of the case manager are discrepant.  That conflict is compounded by the fact that the managers do not have the professional credentials or the accountability of the physicians they are literally ordering around.
    
How do they do it at Google?  I consider engineers and doctors to be equivalent professions.  They  both require years of study and ongoing study.  They both have professional codes of conduct.  If there is any management on the technical side, engineers and physicians both want those people to have the best technical qualifications.  In that context the HBR article was interesting.  At one point Google wanted to try a completely "flat management system" with no managers.  Many of the engineers thought that it might recreate an academic environment similar to graduate school and produce a similar level of excitement and creativity.  That model resulted in upper management being flooded with human resources issues.  They eventually developed a system of managers with few layers designed to reduce micromanagement.  The example given was that some of the managers have up to 30 engineers reporting to them.  According to the engineer interviewed for the article: "There is only so much you can meddle with when you have 30 people on your team, so you have to focus on creating the best environment for engineers to make things happen."  This is a foreign concept in managed care.  Not only are physicians micromanaged but their work environment if frequently manipulated by various managers to decrease both their productivity and work-life balance.  It is a set up for burnout and suboptimal intellectual performance.

The following table is a good example of the differences between how Google manages their engineers to remain a state of the art engineering company with an emphasis on technical expertise.  There are very few medical organizations that have a similar focus.  The ones that do are usually criticized by managed care companies and dropped from their networks for being "too expensive."  As a physician ask yourself which environment you would prefer to work in.  Imagine working on the most exciting and intellectually stimulating team you have ever worked on in your training compared with where you currently work.  As a patient, the question is no less significant.  Do you want a physician who is excited about practicing medicine, who is intellectually stimulated, and not burned out or do you want a physician as they are currently managed?

Google Managers	Physician Managers
Micromanagement is prevented	Micromanagement is the rule of the day
Work environment is optimized for engineering work	Work environment is optimized for managers
Respect for technical expertise and problem solving rather than title and formal authority.	Strictly chain of command often flows from people with no technical expertise.
Good manager empowers the team.	Good manager empowers themselves and their boss.
Helps with career development.	At the minimum does not care about career development and at the worst may try to actively interfere with professional career.
Has technical skills to help and advise the team.	Has no technical skills and often has no medical degree or license.
Productive and results oriented.	Productivity is measured in adjusting physician productivity units

I used to work in a clinic that was analogous to Google in that we were: "A clinic built by physicians for physicians."  Our mission was to provide care to all people irrespective of their ability to pay.  We did not have a lot of resources, but we were good at our mission.  The collegial atmosphere was excellent and we did not make a lot of money.  It was an incredible learning environment where psychiatrists routinely interacted with colleagues from all specialties.  It was acquired by a managed care company and was managed less and less like Google.  Today all of its management parameters rest fully on the right side of the table.

The best management for knowledge workers is known.  Why don't we see it applied to physicians?

And yes, that is a rhetorical question.

George Dawson, MD, DFAPA

Fantasy Foundation For The Preservation of Psychiatry

Psychiatry is on the ropes.  The content of this blog illustrates the prevalent biases against the field that all eventually trickle down to less resources to work with and managed care companies rationing those meager resources in order to make money.  One of my favorite fantasies lately is to think about what I would do to save psychiatry if I ran a foundation with significant resources.  I have thought about it long enough and hard enough to come up with a number of guideposts:

1.  Save the teachers - probably the most beleaguered people in the field these days are the teachers of psychiatrists.  There are a lot of bloggers out there complaining about the "ivory tower" academics who just don't know how life is on the front lines.  The usual gripe is that they make too much money or are in some kind of shady consulting deal.  How dare they dictate to the rest of us how to practice?  That has not been my experience, and I have probably taught as much to medical students and residents as the next guy.  I see people trying to make a living and teach at the same time.  I see people needing to meet absurd "productivity" expectations and teach at the same time.  Teaching in generally is not counted as "productivity" in a managed care environment.  I see people who give up their ability to type up more patient notes at noon so that they can give a lecture to mostly disinterested medical students or fatigued residents.  They end up typing those notes at night on what is supposed to be their own time.

When I ask myself what would help them the most it comes like a flash - free high quality graphics for PowerPoints.  I have a parallel blog with some ideas, but there is nothing like great graphics that are free to use and save your faculty hours of sleep trying to come up with their own and not violate somebody's copyright.  You would think that professional organizations, like the American Psychiatric Association (APA) would support this idea.  Like everybody else, they produce downloadable PowerPoint slides for their major journals.  If you read the small print, you are supposed to go to the CopyRight Clearance Center and pay a fee.  I paid a fee of $45 for a lecture to a class of 12 and $85 to lecture a class of 42.  That was to project the slide and include it in my PowerPoint for the day.  I currently give about 32 lectures a year.  Considering the reimbursement I get for the lecture, it is not a commercial presentation, and I have been paying lots of money to the APA for about 30 years - you would think I could get a break.  As the head a a great foundation, I would purchase the rights to several good resources like Blumenthal's Neuroanatomy Through Clinical Cases or Atlas' MRI of the Brain and Spine and make them freely available to any instructors of psychiatrists.

2.  Free neuroscience conferences - there need to be much better basic science courses to bring clinical psychiatrists up to speed on the latest neuroscience and how it applies to the field.  Typical conferences are centered around some clinical activity that most of us are doing anyway.  Do we really need to hear more about something that we are doing everyday?  Something that we know everything about including the usual limitations?  Why not expand back into a consciousness based discipline looking at innovative ways to conceptualize problems and solutions.  Neuroscience is critical to that and there are several very articulate voices in the area.  I would plan a conference every years that was free to psychiatrists for 2 - 4 days of neuroscience.  There is a lot of neuroscience out there and I would ask some of the top journals like Nature, Science, Neuron, Biological Psychiatry, and Molecular Psychiatry to submit a program of Neuroscience for psychiatrists.  I would award the grant competitively to the best submitted program.

3.  Free computerized psychotherapy and an affiliated institute of psychotherapy using computers - I previously posted about John Griest's work in computerized psychotherapy and its effectiveness.  The whole point of the post was to emphasize a significant source of non-medication based treatment that is essentially not limited by manpower requirements.  There are several groups who have implemented this already, but to my knowledge none of them are major U.S. health care organizations or managed acre companies.  The commonest managed care approach is to give everyone a non specific depression rating scale, call that a quality marker, and then put as many people on antidepressants as soon as possible.  There is enough IT available that a foundation could take the lead in this area, develop the programs, and accept referrals from psychiatrists across the country for specific types of computerized psychotherapy.   

4.  Free clinical workgroups -  I have posted on the University of Wisconsin Memory Clinics collaborative clinical network across the state that focuses on maintaining a high level of expertise in all of the cooperating clinics for the diagnosis and treatment of Alzheimer's Disease and other dementias.  There is no reason that model cannot be extended to Depression, Bipolar Disorder, Post Traumatic Stress Disorder, or Attention Deficit Hyperactivity Disorder.  When people talk about collaborative care, they are usually talking about a managed care model that marginalizes psychiatrists.  A recent post suggested that some of the promoters of the managed care model have challenged naysayers to come up with an alternative.  I am a naysayer to anything that resembles managed care and the UW model is definitely a competing model that emphasizes psychiatrists at the top of their game in diagnosing and treating mental disorders.  That would be my priority over a managed care model that is so watered down, you don't even need a psychiatrist on the premises.

5.  An independent certification process - The American Board of Medical Specialties (ABMS) has a chokehold on all board certification processes with the exception of the American Board of Addiction Medicine (ABAM).  ABAM has their own certification and recertification process.  The current controversy involves the recertification process and whether it should be a standard blind exam with no learning aspects and a review of patients in a physicians practice or not.  I have posted some details about this to show how highly politicized it has become.  There is really no good evidence that recertification beyond the usual CME requirements is needed.  Although the American Board of Psychiatry and Neurology (ABPN) and the APA has gone along with ABMS ideas, most members find the process onerous and not conducive to learning, especially when they are in a labor intensive work environment that allows little time for study.  Any professional organization should be innovative enough to come up with an ideal process that would keep members up to speed professionally while not intruding on their limited time.  My foundation would develop a recertification system based on the APA's Focus journal an develop a process that would allow members to study on their own time and recertify by taking the Focus examinations.  It should eventually be possible to incorporate modules from the ongoing neuroscience seminars and what is learned in the computerized psychotherapy lab as study modules.

Using these innovations and hopefully more, my foundation would seek to improve the technical expertise of all psychiatrists, highlighting what is possible for the future and bring every clinician out of the current misery of political overegulation and managed care overproduction.  The whole idea that we currently have a professional organization and a specialty board that are not protective of psychiatrists is one thing.  The idea that they are actually doing things that are counterproductive to the ongoing professional education of psychiatrists and increasing burnout by creating a more stressfull practice environment is another.

My fantasy foundation would hope to reverse those trends.

George Dawson, MD, DFAPA

"Low T Syndrome" and the Fountain of Youth

Psychiatrists are seeing increasing numbers of male patients who are being treated for low testosterone.  The symptoms of "Low T" are being promoted as a reason to get assessed and treated with testosterone.  Not surprisingly, "Low T" is a highly successful pharmaceutical company promotion.  So successful that testosterone seems to have disappeared from the vernacular, replaced by "T".  I have had the opportunity to follow this controversy for the last 30 years.  Back in the days when there were a subgroup of psychiatrists who considered themselves to be "microendocrinologists" testosterone, LH, FSH, and GnRH were studied along with the components of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes,  particularly in depressives.  Despite a lengthy but low intensity research effort on gonadal steroids in both men and women the data on baseline neuroendocrine correlates and results of supplemental treatments are equivocal.  That said, most psychiatrists have encountered women who have often had a significant response to treatment with gonadal steroids.  Seeing a consistent treatment effect is difficult.

As a clinical psychiatrist, I have found that the clearest information on drugs is available in the FDA approved package insert.  In the case of the product being marketed by the "Low T" ads is a form of testosterone gel that is available in two different strengths.  The only indication for the the product according to that package insert is primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congential or acquired).  Any use for treating depression or augmenting antidepressants is off label use.  If testosterone was effective as an augmenting agent it would join the ranks of most antidepressant augmenting agents as being an off label prescription.  There are three related issues.

The first is the diagnosis of primary or hypogonadotropic hypogonadism.  In most cases, my speculation would be that a middle aged man sees or hears about the "Low T" ad and goes in to see their primary care physician and a testosterone level is ordered.  Most authoritative sources like UpToDate state that testosterone replacement should only occur in men who are hypogonadal.  Making that determination generally requires two low testosterone levels or in the indeterminant cases some expertise in the hypothalamic-pituitary-gonadal axis (HPG), as well as access to a laboratory with some specialized endocrine capabilities.  This is the level where most assessments seem to break down.  The range I am used to seeing is total testosterone levels ranging from about 300-1,000 ng/ml.  Scattergrams of testosterone versus behavioral parameters of interest like libido, aggression, and energy usually show low levels of correlation.  Many men are getting treated for (like the commercial suggests) low testosterone, or a level in the low normal range but not in the deficient range.  That takes treatment into the realm of off label indications because they do not have a diagnosis of hypogonadism.  A definitive algorithm (1) from endocrinologists is available including when to refer to an endocrinologist.

The second issue is whether there is any evidence testosterone either treats depression or is an effective agent to augment the effects of antidepressants.  That would conceivably move testosterone to the level of the augmenting agents used in the STAR*D study of depression.  The best guidance in the literature comes from Pope, et al (2) article on testosterone replacement in men 65 years of age or younger taking serotonergic antidepressants, a total testosterone level of less than or equal to 350 ng/ml, a PSA less than 4.0 ng/ml and an incomplete response to the antidepressant.  The author's conclude that there were no significant differences in response to testosterone or placebo gel.  Their conclusion is that the current practice of testosterone supplementation of antidepressants is not supported, but that there may be identifiable subgroups in larger studies.

Pope's observations are also critical in that he is an expert in anabolic androgenic steroid (AAS) abuse and has observed a euphorigenic hypomanic response to both AAS and prescription testosterone.  In his article he cites this response occurring in about 4.8% of 105 volunteers taking the equivalent of 500 mg/week of testosterone or an equivalent.  These observations are critical because they factor in addictive behaviors associated with substance use and Pope's group has proposed criteria for anabolic-androgenic steroid dependence.  The criteria highlight that fact that there are a number of associated mood symptoms including depression during the withdrawal phase.  Screening for an AAS use disorder and associated comorbidity like muscle dysmorphia

The third issue is the risk benefit analysis and that makes testosterone as an augmenting agent more unique than the other STAR*D agents.  Testosterone has unique medical risks beyond any risk of an additive effect with an antidepressant.  The main risk with other augmenting agents is usually rare cases of serotonin syndrome or side effects specific to the agent.  They are essentially being prescribed for the same indication.  With testosterone, there is no professional body advocating for supplementation in men with a eugonadal state and the risks may be significant starting with the contraindications (breast cancer, known or suspected prostate cancer) and warnings (benign prostatic hypertrophy, exposure to women and children, edema, sleep apnea, and the need to monitor a number of biochemical parameters).  There have also been recent articles showing a possible correlation with a number concerns about increased myocardial infarction, ischemic stroke, and other mortality (3,4,5).

So for all of you psychiatrists out there who are being referred men who are being treated for "Low T" or being sent to you with a question about testosterone there are a couple of necessary steps at this point.  Make sure that a diagnosis of hypogonadism has been established.  Let your patient know that testosterone supplementation of antidepressants in eugonadal men at this time is experimental and carries risks.  I would also inquire about a past history of anabolic androgenic steroid use, their conscious experience of that use ranging from mood changes to body image concerns and any prior psychiatric history including a history of addictions or using performance enhancing drugs.  For men considering an evaluation and treatment for "Low T" it is much more complex than filling out an online questionnaire on pharmaceutical company website.  Have realistic expectations about what you can expect, especially if someone is suggesting that testosterone supplementation is a treatment for depression.  Take a good look at the risk and consider that there will probably never be a major study that takes a good look at this issue with a large population of men.  The prospective studies will probably be similar to Pope, et al of about 100 men followed for a short period of time and the retrospective studies will have some innovative designs but they will also be limited by selection factors and significant stratification factors.  That generally means that additional information about risk may only be available in the form of FDA warnings from post marketing surveillance or their own analysis of data that may not be publicly available.

George Dawson, MD, DFAPA

References:

1.  Dandona P, Rosenberg MT. A practical guide to male hypogonadism in the primary care setting. Int J Clin Pract. 2010 May;64(6):682-96. doi: 10.1111/j.1742-1241.2010.02355.x. Review. PubMed PMID: 20518947; PubMed Central PMCID: PMC2948422

2.  Pope HG Jr, Amiaz R, Brennan BP, Orr G, Weiser M, Kelly JF, Kanayama G, Siegel A, Hudson JI, Seidman SN. Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment. J Clin Psychopharmacol. 2010 Apr;30(2):126-34. doi: 10.1097/JCP.0b013e3181d207ca. PubMed PMID: 20520285

3.  Vigen R, O’Donnell CI, Barón AE, et al. (2013) Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 310:1829-1836.

4.  Basaria S, Coviello AD, Travison TG, et al.  Adverse events associated with testosterone administration. N Engl J Med. 2010 Jul 8;363(2):109-22. doi: 10.1056/NEJMoa1000485. Epub 2010 Jun 30. PubMed PMID: 20592293; PubMed Central PMCID: PMC3440621.

5. Cappola AR. Testosterone therapy and risk of cardiovascular disease in men.  JAMA. 2013 Nov 6;310(17):1805-6. doi: 10.1001/jama.2013.280387. PubMed PMID: 24193077.

Tip:  Follow the lead authors of these references on Medline and you will have a comprehensive look at the literature in this area.

Evidence based Maintenance of Certification – A Reply to ABMS

The politics of regulating physicians is no different than politics in general and that typically has nothing to do with scientific evidence.  From the outset it was apparent that some people had the idea that general standardized exams with high pass rates and patient report exercises would somehow keep all of the specialists in a particular field up to speed.  That assumes they were not up to speed in the first place.

As a member of a professional organization embroiled in this controversy it has give me a front row seat to the problems with physician regulation and how things are never quite what they seem to be.  From the outset there was scant evidence that recertification exams were necessary and with the exams no evidence that I am aware of that they have accomplished anything.  The American Board of Medical Specialties (ABMS) actually has a page on their web site devoted to what evidence exists and I encourage anyone to go there and find any scientific evidence that supports current MOC much less the approaching freight train of Maintenance of Licensure or linking MOC to annual relicensing by state medical boards.  Feel free to add that evidence to the comments section for this post.

Prior to this idea there were several specialty organizations that had their own programs consisting of educational materials that were self study courses that could be completed on specific topics relevant to the specialist every year.  A formal proctored examination and all of the examination fees that involves was not necessary.  The course topics were developed by consensus of the specialists in the field.  A couple of years ago I watched a CME course presentation by a member of the ABMS who pointed out that three specialty boards (of a total of 24) wanted to continue to use this method for relicensing and recertification.  They were denied that ability to do that because the ABMS has a rule that all of the Boards have to use the same procedure that the majority vote on.  The problem was that very few of the physicians regulated by these Boards were aware of the options or even the fact that there would be a move by the ABMS for a complicated recertification scheme and that they would also eventually push for it to become part of relicensing in many states.

If the ABMS is really interested in evidence based practice, the options to me are very clear.  They currently have no proof that their recertification process is much more than a public relations initiative.  Here is my proposal.  Do an experiment where one half of the specialists to be examined that year complete a self study course in the relevant topics for that year.  That can be designated the experimental group.  The other half of the specialists receive no intervention other than self study on their own for whatever they think might be relevant.  Test them all on the topics selected for the self study group and then compare their test scores.   See who does better on the test.  Secondary endpoints could be developed to review the practices of each group and determine whether there are any substantial differences on secondary measures that are thought to be relevant in the tested areas.

Until this straightforward experiment is done, the current plan and policies of the ABMS are all speculative and appear to be based upon what has been called conventional wisdom.  Conventional wisdom appears to be right because all of the contrary evidence is ignored.  There is no scientific basis for conventional wisdom and it falls apart under scrutiny.  Physicians in America are currently the most overregulated workers in the world.  The rationale for these regulations is frequently based on needing to weed out the few who are incompetent, unethical, or physically or mentally unable to practice medicine.  Many regulatory authorities grapple with that task and maintaining the public safety.  In many cases it is a delicate balance.  But we are far past the point that every physician in the country should be overregulated and overtaxed based on conventional wisdom because regulatory bodies are uncomfortable about their ability to identify or discipline the few.   If the ABMS or any other medical authority wants evidence based safeguards for the public based on examination performance – it is time to run the experiment and stop running a public relations campaign to support the speculative ideas of a few.

George Dawson, MD, DFAPA    

Neuron Perspectives in Neuroscience

Eric Kandel's thought, research, and writing have been a major source of inspiration to me ever since I read his neuroscience text and his classic article Psychotherapy and the Single Synapse in the New England Journal of Medicine nearly 34 years ago.  I was very pleased to see that he wrote the lead article in Neuron's   25th Anniversary edition entitled "The New Science of the Mind and the Future of Knowledge."  I read the article in the same spirit that I read the original NEJM article, guidance from a world class neuroscientist who was also trained as a psychiatrist.  At that level the article is quite exciting because somewhere along the line Dr. Kandel has clearly been following concepts that are far removed from the synapse and does a good job of summarizing the major points and the current deficiencies.  He also comes back to the idea that psychotherapy is a biological treatment as he proposed in the original 1979 article.

One of the most interesting aspects of the article is that Kandel does not apologize for psychoanalysis.  He is also not excessively critical.  I read an article about his residency class at Harvard and psychoanalysis was certainly prominent at the time.  Although it is fashionable these days to throw Freud under the bus, he points out that Freud and subsequent analysts were right about a number of issues that neuroscience has caught up with including:

1.  Unconscious mental processes pervade conscious thought.
2.  The importance of unconscious thought in decision making and adaptability.

The probable link here is that Freud, psychoanalysis, and current neuroscience is focused on the mind rather than descriptive psychiatry.  At some point the majority of the field got sidetracked on the issue of identifying a small number of pathological conditions by objective criteria.  The mind was completely lost in that process and those few psychiatrists who were focused on it were engaged in generating theories.  He criticizes the field for a lack of empiricism but recognizes that has changed with clinical trials of psychodynamic psychotherapy and recent interest in testing psychoanalytical theories with the available neuroscience.  He also points out that Aaron Beck was a psychoanalyst when he developed cognitive behavior therapy focused on conscious thought processes and became a leading proponent for an evidence based therapy.

It was good to see a discussion of the hard problem of consciousness.  I was on the ASSC listserv for many years until it eventually lost a home and was shut down.  Many of the experts in consciousness studies posted on that thread but there was very little neuroscience involved but plenty of discussion of the neural correlates of consciousness.

Information flow through the brain has always been one of my interests.  The idea that information flows through biological systems at both chemical and electrical levels is a relatively recent concept.  At the clinical level behavioral neurologists like Mesulam and Damasio discussed it based on cortical organization and information flow primarily at cortical levels.  I taught a course for many years that talked about the basic information flow through primary sensory cortex, association cortex and then heteromodal cortices.  The model had good explanatory power for any number of syndromes that impacted on this organizational model.  For example, achromatopsia made sense as a lesion in pure sensory cortex and posterior aphasia made sense as a lesion of heteromodal cortex.

Using this model, overall information flow from the sensory to the motor or output side could be conceptualized, but there were plenty of open boxes in the flowchart along the way.  The theory of how consciousness is generated from neural substrates was still a problem.  Social behavior was another.  Despite decades of descriptive psychiatry, the diagnostic criteria for major psychiatric disorders still depended on symptoms.  In many cases aberrant social behavior was a big problem and often a more accurate reflection of why patients were disabled, unable to work and had limited social networks.  Even though there were scales to rate positive and negative symptoms in schizophrenia, aberrant social behavior cut across a number of major psychiatric disorders.  In my first job as a community psychiatrist, we rated social behavior of the people in our community support program and it was a better predictor of disability than diagnosis or ratings of positive symptoms.  The neuroscience of social behavior remained resistant to analysis beyond the work done on cortical lesions and obvious comparisons to those syndromes.  But people with schizophrenia had no obvious frontal lesions.

Dr. Kandel points out the developments in these areas ranging from de novo point mutations affecting circuitry in the frontal cortex to mirror neurons to the neuroendocrinology and genetics of social behavior.  The review of Thomas Insel's work with voles and the extension of that work by Bargmann in C. elegans highlights the importance of specific systems in social behavior and how these systems are preserved across species.

One of the most interesting areas outlined by Dr. Kandel was the issue of art and the neuroscience of its creation and perception.  I have just posted on abstract art and was able to locate a quote from Kandinsky:

"The abstract painter derives his "stimulus" not from some part or other of nature, but from nature as a whole, from its multiplicity of manifestations which accumulate within him and led to the work of art.  This synthetic basis seeks its most appropriate form of expression which is called "nonobjective".  Abstract form is broader, freer, and richer in content than objective [form]." (Kandinsky Complete Writings on Art - p 789)

Kandel develops a narrative based on Viennese art historians and the importance of the aesthetic response to art.  That response is an emotional one based on the life experience of the viewer and the neuroscience of that response can be studied.  He looks at the inverse optics problem, facial recognition, and comes up with a flow diagram of the processes involved in viewing visual art.  I did not realize it until I read this article but he has a new book on the subject and ordered a copy to review at a future date.

Some of the conclusory remarks about neuroscience and what it means to society are the most important.  It is easy to be cynical about any scientific endeavor and it is also very easy to be political.  Neuroscience has to endure (although to a much lesser degree) than what psychiatry endures.   There are people out there commenting on neuroscience who don't seem to know much about it.  In many cases they are not scientists.  Even in the case of scientists, it is often easy to forget that the public will probably not hear the most objective and the most scientific.  They will typically hear from the experts who unambiguously support one side of the scientific argument as opposed to the other.  Kandel is cautious in his suggested applications of neuroscience to society.  He does not view it as a panacea or an explanation for behavior necessarily.  An example:

"Attributing love simply to extra blood flow in a particular part of the brain trivializes both love and the brain.  But if we could understand the various aspects of love more fully by seeing how they are manifested in the brain and how they develop over time, then our scientific insights would enrich our understanding of both the brain and love."    

Hopefully you will have time to read this paper.  I have highlighted a few more based on my reading about neuroscience over the past 20 years or so.  I will end with a paragraph on technical expertise.

When I was interviewing for residency positions 30 years ago, one of my questions that drew the strongest emotional reaction was: "Does your program have a reading list for residents?"  That question on average elicited shock or at least irritation from the average residency director.  The only exception was Johns Hopkins.  They handed me a neatly bound list of several hundred references that they considered key references that every psychiatric trainee should read.  I should have taken it as a sign and applied there, but my trajectory in life has been more random and circuitous than studied.  If I was a current residency director, I would have a list with a neuroscience section and the following articles from this volume of Neuron would be on it.  People often recoil when I talk about the technical expertise needed to be a psychiatrist.  Technical seems like too harsh a word for most psychiatrists.  Most of the media debate after all is essentially rhetorically based political discussions  I would say that if you read these articles, you can consider them to be a starting point for what you might need to know about neuroscience and psychiatry in the 21st century.

George Dawson, MD, DFAPA

A reading list for psychiatrists of the future (all available free online at the above link):

Kandel, Eric (2013) The New Science of Mind and the Future of Knowledge.  Neuron 80: 546 – 560

                             

McCarroll Steven A, Hyman Steven E (2013) Progress in the Genetics of Polygenic Brain Disorders: Significant New Challenges for Neurobiology. Neuron 80:578-587.

Südhof Thomas C (2013) Neurotransmitter Release: The Last Millisecond in the Life of a Synaptic Vesicle. Neuron 80:675-690.

Huganir Richard L, Nicoll Roger A (2013) AMPARs and Synaptic Plasticity: The Last 25 Years. Neuron 80:704-717.

Dudai Y, Morris Richard GM (2013) Memorable Trends. Neuron 80:742-750.

Shadlen Michael N, Kiani R (2013) Decision Making as a Window on Cognition. Neuron 80:791-806

Buckner Randy L (2013) The Cerebellum and Cognitive Function: 25 Years of Insight from Anatomy and Neuroimaging. Neuron 80:807-815.