A North American Cruise

Not going on a cruise was a always a high priority on my bucket list.  I am reporting that (for many reasons) I have failed in that pursuit.  My wife and I just got back from an 10 day excursion into Alaska by sea and out by land.  The first leg was a 6 day cruise from Vancouver, British Columbia to Juneau, Alaska and overland from there to Denali (Mt. McKinley) and back to Anchorage with a direct flight back to Minneapolis.  I started typing this as we left Ketchikan, Alaska headed for Icy Straight Point, Alaska. There is a mountain range silhouetted by the sunset outside my window.  The shore line seems to pass by at a rate much faster than the reported 16 knots, but that is not bad for a vessel weighing 93,000 tons.

Cruise ships these days are engineering marvels.  The one that I was on was 11 stories high.  It had a walking/running track on the top deck (200 meters/lap) with extensive spa and gym facilities.  The technical details of this ship are hard to find, but a little research showed that it was powered by 2 x 19 MW azimuth thrusters rather than propellers.  That explained the easy maneuverability of this nearly 1,000 ft long ship.  In front of the Hubbard Glacier, the captain was able to spin the boat in a circle for a couple of revolutions.  Sitting on the aft deck, the propulsion units have enough thrust to create prop wash that extends to the horizon.  A tour of these capabilities and the engineering involved would have been fascinating (for a few of us) but I understand the security constraints.

In the 5 months leading up to September each year about a million cruise ship passengers make this journey. As a psychiatrist who likes to keep track of cultural phenomena, this was one that I had missed.  The ship lines involved have created ports along the way with excursions to highlight the area resources and make the natural attractions readily available to a number of interests. A few examples include excursions into the world’s largest temperate rain forest capped off by a meal of fresh Alaskan crab. On that excursion today I learned some interesting facts. Ketchikan and the surrounding area on the island have a total population of about 10,000 people during tourist season, but when that is over the whole lower town built around the cruise industry shuts down and many people leave until next year. It rains almost 7 days a week in Ketchikan and the total annual rainfall is about 13 feet. One of the natives told me that people need to take Vitamin D and volunteered the typical dosing ranges of 2,000-5,000 IU per day. Some of the outliers were taking 10,000 IU. She said nothing about levels being drawn or cases of toxicity. The weather for this cruise was outstanding - generally sunny with temps in the 70s except for the period next to the glacier.   The town itself seemed to be organized like many small American towns.  The government buildings and fire department were most prominent.  I wondered what it might be like to be a psychiatrist in Ketchikan.  But I did not have too long to think about it, because in 4 hours we were back on the boat headed for Icy Straight Point.

In the meantime, I am nearly at the 50 day point of walking about 12,000 steps per day.  I decided to head up to the running track on the 11th floor of the ship and cover some ground.  This is the third day I am doing it.  There are a lot of people huddled in deck chairs in the bright sunlight. Even though the air temp is in the high 50s to low 60s, there is a stiff breeze blowing directly over the bow.  The only reasonable wear is heavy fleece or a windbreaker and a sweater.  I decided to sample my fellow passengers as I walked using an old survey method from wildlife biology.  From a demographic standpoint about 25% of the population was less than 40 years of age and half of that sample was less than 18.  At one point the cruise line had a special activity for the younger adults. Despite the age structure of the crowd, in the warmer climate pulling out of Vancouver, there was a steady loud beat of dance music on this deck, all compiled by a young disk jockey.  With this mix of ages there are always a number of clashes between the generations.  The energetic 10-15 year olds running randomly around the deck among the older folks.  A few grumbling old folks commenting negatively on the number of tattoos, especially on younger women.  Tall, thin, spectacled and silent post-adolescent girls are walking around in Converse high top basketball shoes.  Boys in that same age group are swaggering, swearing, and discussing Ivy League fashion.  The majority of the crowd was older and very well mannered.  There were a couple of groups celebrating anniversaries and weddings.  I had learned from another physician from a similar cruise that there were several people who required dialysis and there was a nephrologist on board to monitor that treatment.  The place was crawling with extraverts.  At times it was difficult to avoid conversations.  I saw a fellow introvert bundled up on a deck chair, facing away from the crowd and reading a book in the bright sunlight.  I could feel his pain.

Like most inescapable public gatherings the cruise creates quite a bit of tension within me.  At one point in my life I was a very active outdoorsman.  I was a tree hugger of the highest degree.  I was a white water kayaker and canoeist.  I nearly drowned three times in one day on the Montreal River in Upper Michigan and went back for more white water kayaking after that.  But at some point, all of that changed.  The landscapes seemed to be the same.  Hawaii was like Wisconsin with volcanoes. Colorado was like Wisconsin with mountains.  The terrain always looked better on television.  Alaska present thousands of miles of coastal mountains, some of which have the highest number of peaks greater than 10,000 feet of any mountain range in North America.  The glaciers were also unique, especially glaciers coming right out to the edge of the ocean, breaking off and creating waves, ice floes, and icebergs.  The ship navigated right into this area among the chunks of ice and spun around a few times before heading to Seward.

Polychrome Pass - Denali National Park

In everyday life I am still out there and very active, but the conditions have to be right and I have to be able to measure everything – miles, heart rate, cadence, speed, and all of the derivatives.  I avoid the hours from 10 AM to 3 PM or whenever my shadow on the ground is shorter than my actual height – a standard Dermatology tip on avoiding skin cancer.  I am no longer cycling in the rain.  The goals were more complicated.  I can no longer go out in the woods and plant trees with a grub hoe ignoring the biting flies and mosquitoes.  The parallel dimension was the demands of inpatient psychiatry.  There were decades of complicated problems, no solutions and confronting aggression and hostility at all levels on an almost daily basis.  I lived to go home, shut the door and enjoy the solitude.  Being stuck on a cruise ship where nearly everyone is an extrovert and trying to engage me in conversation is the antithesis of the last 25 years of my existence.  I am quite happy to be ignored but on a cruise ship it is common to encounter at least 10 crew members all of whom meet you very cheerily and begin with some variation: “Good morning sir. How are you today? Can I help you with anything?” I am sure that is standard cruise training is designed and implemented by extroverts.  Extroverts seem to dominate the customer relations fields and that’s why there is all of this unnecessary talk.  If I was consulting I might suggest an I (Introvert) Badge that translates to “You don’t have to ask me – if I have a problem I will ask you.” Or in the case of extreme Introverts “You don’t have to greet me – we are cool and I don’t think I am better than you.”

The entire cruise atmosphere was a study in contrasts for me.  On the one hand we were cruising through some of the most desolate places on the planet, ideal turf for introverts wanting solitude.  On the other we brought a party with us and even a party director who seemed bent on providing the maximum number of activities and entertainment per day.  That led me to think about people who might be stressed by the cruise.  Did anyone have anxiety or panic attacks?  I never made it down to talk with the ship's doctor about those problems, but it was easy to see how they might occur.  I also had the thought about people getting on the boat who were already depressed.  Would it lead to any adverse outcomes.  According to Wikipedia, there was at least one reported incident of a person who had gone missing on a cruise and who was seen jumping overboard when the security camera footage was reviewed.  I could find only one article on this phenomenon in Medline.  There is an associated literature that suggests that the mental health of seafarers in general, but primarily on merchant ships, may be poor as evidenced by suicides as a percentage of total deaths or deaths due to illness.  That author also suggests the numbers may be significantly higher if disappearances at sea are counted.  Suicide was also a topic during the tour.  Our tour guide said that Alaska had the highest suicide rate among the 50 states.  According to the CDC that is not strictly true but they do have the second highest rate at 23/100,000 or roughly double the age-adjusted suicide rate for the entire country.  They also have ready access to firearms.  Any Alaskan can carry a firearm concealed or unconcealed without a special permit.  One of our guides took a temporary break from the work to do a stint transporting mentally ill Alaskans to hospitals for treatment.  At this point, I can look back and see the opportunity to do a lot of good in Alaska if you are a psychiatrist who likes winter weather and are motivated to the point where you don't need a lot of collegial support.  But it is definitely a job for a younger person than I am.

Food is always a big point of discussion on cruises.  I can understand the advantages of not having to purchase or prepare it.  But the usual commentary is on how abundant it is and how good it is.  I am a very finicky eater and give it mixed reviews.  It was clearly abundant with large cafeteria style dining available all day long.  There were typically many entrees available followed by many deserts and pastries.  There was an ice cream bar and other specialty (pasta, eggs Benedict, pizza) stations on the side.  Food consumption there was unlimited and there were no additional charges.  You just walk into the cafeteria as many times a day as you like and you don’t have to pay anything for food.  In addition, there were two formal dining areas that needed reservations with more limited but high end entrees and appetizers.  Food consumption in those venues was limited to the standard restaurant style meal at no additional charge.  Finally there were four more restaurants that required additional payment for additional high end cuisine with consumption limited to that meal.  Beverage packages required the use of a pass card and prepayment of various beverage packages.  It should come as no surprise that cruises are risky for people trying to control their weight.  Before getting on this cruise a coworker told me that when her mother came back from a cruise she was almost “unrecognizable” due to weight gain.  Unless there is a conscious plan to limit consumption and exercise weight gain must be the rule on most cruises.

As far as the quality of the food, I give mixed reviews.  I am not much of a carnivore, but I do consider myself to be an expert in breakfast type foods, pizza, pasta, chicken, fish, and desserts.  If I compare the meals from the specialty sit down restaurants with restaurants within a 10 mile radius of my home it is clearly inferior.  That is not to say it was not good, just not excellent.  Almost everybody on a cruise raves about the food.  Their opinions may be biased by the overall cost of the cruise, the emphasis on food onboard (galley tours, discussions with the chef, wine tastings, etc), availability to well past the satiation point, and the ease of availability by no acquisition or preparation time by the onboard guest.  In addition, one of the few consistent television programs available onboard was Top Chef and it was on 24/7.  It has been trendy in the press to slam Americans for gluttony and obesity, but I won’t go there.  About 90% of the guests were Americans and Europeans from various ethnic origins, followed by Asians from various countries and then guests from Spanish speaking countries.   The cuisine was a mixture of American, Thai, Indian, and Japanese foods and it got good reviews from people originating from those countries.   I don’t think anyone was in an eating frenzy, just consistent consumption.  The majority of the food selections were very healthy and the main problem for consumers was portion control and limiting carbohydrates.

Alcohol consumption also seemed well controlled.  There were hierarchies in the beverage packages, most cost for the high end package containing alcoholic beverages.  There was a shopping area that sold expensive alcoholic beverages in large bottles with a duty free advantage, but I never saw anyone in that shop. Most of the drinking occurred in the deck and spa areas and with meals.  There was a meeting listed for anyone who was a friend to Bill W.  That may not be the rule on all cruises.  I listen to a morning talk show on the way to work and heard that the people on that show were aware of some "rock and roll" cruises that needed to make extra stops to pick up more alcoholic beverages.  This was a cruise that seemed to target families and multiple generations.

There is a curious tradition of formal dining that persists to this day.  I have been told that early cruises had assigned seating in the dining areas and at times that involved eating with the captain.  In those days everyone had to be dressed formally for it – for men that meant a sport coat and tie.  That tradition persists today but only on 2 days of the cruise.  It seems an unnecessary artifact to me.  The captain doesn’t eat with the guests.  I was told by one of the crew that they believe it encourages more socially appropriate behavior and a classier atmosphere.  My guess it that it probably has no more impact than the “no shirt, no shoes, no service” rules posted in various part of their literature. The extra attire takes up valuable room in the suitcase of nothing is really added.  My guess would be that all of this window dressing is the work of Extroverts (“Isn’t dressing up in formal attire fun?”).

After looking at a number of other comparisons like entertainment, electronic devices and Internet access, total cost of the cruise and associated excursions – I realized that an obsessive approach could be taken in the analysis. There are several web sites that take this approach.  The overriding question for me was what are the real differences between people who like cruises and people who don’t.  Whenever I give my opinion there is a general outcry that I am unreasonable and that my wife is a saint for putting up with me.  How could I not like a cruise?  And like most things it is a question of preferences.  My preference for eating carbohydrates dates back to an early age and I know the correlates and I think I know how all of that works at some level.  I also realize that those same mechanisms can produce preferences in billions of my fellow humans that are not my preferences and in this case it means that (at least on the surface) many more people seem to prefer cruises more than I do.



George Dawson, MD, DFAPA


Supplementary 1:  This post was originally completed aboard a cruise ship sailing for Glacier Bay, Alaska - just off the coast from Gustavus, Alaska about 48 miles west of Juneau.

That is me holding up the sign to Yukon (formerly known as the Yukon Territories) just north of Juneau and 600 miles south of the city of Dawson (formerly known as Dawson City).  My ancestors were given the name Dawson on Ellis Island, because their name was not pronounceable, so the founder of Dawson City is not a relative.

Supplementary 2:  Sometime after posting this, I discovered that the late David Foster Wallace had been interviewed by Terry Gross on her public radio program Fresh Air.  In that interview he talks about an article he wrote on going on a cruise and discusses that about 1/4 of the way down in the transcript.  He also wrote a piece called Shipping Out: On the (nearly lethal) comforts of a luxury cruise.  All of that writing can be found by search engines.  David Foster Wallace is an acclaimed writer and his writing about cruises is both accurate and entertaining.  It has an added dimension (especially in the Fresh Air transcript) of considering whether fun and enjoyment can be managed.

Admission, Discharge and Readmission Policies - No Better Example Of Business Driven Pseudoscience

One of the recurrent themes of this blog is that the application of science to medicine, especially at the public policy level has plummeted over the past three decades.  That has been directly attributable to the influence of business on all levels of government.  One of the more pervasive themes is that the behavior of health professionals is best accomplished by incentivization.  In other words financially punish physicians to get them to change their behaviors that you don't want or financially reward the behaviors that you want them to produce.  I haven't looked at the scorecard lately, but my guess is that the punishments greatly outweigh the rewards.  Maybe my perspective has been skewed by working for an HMO for many years that considered it a reward if they "held back" part of your salary and then gave it to you if all of the physicians in your group met the desired productivity targets.  I am sure it took the MBAs a while to dream that one up.  The equation seems to be as simple as -  "OK here is what we want the goal to be.  We don't want to pay out any rewards anymore.  Let's just penalize people for not meeting the goal until eventually everyone is compliant with the goal."  There is probably no better example than the Medicare Hospital Readmissions Program.

A recent editorial in JAMA notes that the 2013 readmission rates for Medicare patients is about 18% within 30 days (1).  That is associated with a potential cost of $26 billion.  Since 2010 Congress has levied a 3% of Medicare reimbursement penalty on hospitals who have readmission rates that are considered too high.  The problem is that 80% of hospitals are being penalized are safety-net hospitals or those that have a disproportionate share of low income patients.  Those hospitals are more likely to be penalized all three years since the penalty started  and they are more likely to be the hospitals with the lowest operating margins.  The likelihood of penalty also correlates with the percentage of patients treated who are elderly and live with poverty or disability.  

The authors opine that hospitals should not be penalized "because of the demographic characteristics of their patients."  They point out that the evidence suggests that is exactly what is happening and they conclude:  “Targeting hospitals for penalties, even if indirectly, simply because those hospitals care for more poor people is not good policy”.  They use this as a foundation to build their argument for a proposed policy initiative – The Hospital Readmissions Program Accuracy and Accountability Act of 2014.  It builds in safeguards for hospitals treating patients from a disadvantaged socioeconomic status.   

The obvious problem with the authors’ logic here is that they seem to not realize that discrimination against patients of the lowest socioeconomic status has been institutionalized and occurring for decades.  The people I am referring to are those people with addictions and severe psychiatric problems.  The facts are clear.  For the past 30 years, even though psychiatric disabilities rank as some of the top 10 disabilities by any measure, they get a much smaller fraction of the health care dollar for care.  I have used the example of a middle-aged man or woman being hospitalized through the emergency department for acute chest pain.  I don’t know the fraction of those people who are discharged the next day.  But consider that basic scenario if the evaluation of chest pain turns out to be non-cardiogenic.  In the hospital where I have worked that generally means an evening on telemetry and serial troponins and either a stress echocardiogram the next day or an echocardiogram and a stress test.  Price tag about $25-30,000 for less than 48 hours in the hospital.  On the other hand,  let’s say a person has an exacerbation of an affective psychosis and is not able to function at home or has put themselves at risk.  The will be hospitalized in a very low tech psychiatric unit, the goal of which is to discharge them when they are no longer “dangerous” or to discharge them upon request if they cannot be held involuntarily.  Irrespective of the price tag for this care the best available data I have on the DRG reimbursement for this care is about $4,800 irrespective of length of stay.  The economic incentives all line up to rarely provide them with the discharge resources they require to maintain even a subsistence life style and remain stable enough to stay out of emergency departments or jails.  Furthermore in many cases, states previously charged patients a for a portion of their medication costs per month out of their disability income.  The direct and indirect costs incurred by patients and families with severe mental illness and addictions are a travesty of the highest magnitude.  The rationing mechanisms that have been in place for the past three decades have results in care that is subpar relative to any other medical specialty.  It has created an entire population to patients with chronic illnesses that are discriminated against.  The financing of care for them has set a number of perverse incentives that would seem to be more destabilizing such as an incentive for hospital discharge in order to beat the designated days in the diagnosis related group (DRG) and readmit them if necessary.  If the entire DRG incentivization for admissions and discharges is pseudoscientific sleight-of-hand based on very crude demographic variables - why would we expect readmissions policies to be any different?

The second dimension of this care is just how unscientific care based on demographic factors is in the first place.  I was previously in a practice where “consultants” who had never practiced medicine came in and commented on the “complexity” of our patients.  At the time I was caring for many patients who I knew would never be admitted to other general psychiatric units in any other hospital in the state due to their medical complexity.  The consultants concluded that my patients were no more complex than any other patients in the state even though they could not define the measures they used to make that determination.  Nobody mentioned the inherent conflict of interest when a pro-discharge administration hires consultants that agree with their world view - discharge patients as soon as possible.

In another scenario and on a committee, I asked if the demographic determined characteristics and time lines for treating community acquired pneumonia led to any differences in mortality or complications – and nobody knew.  The original Big Data approach in medicine looked at HEDIS variables.  Any practicing physician knows this is an incredibly crude approach that in many cases is meaningless.  There is no better example than saying that treating acute and chronic psychosis in a few days makes no difference in outcomes, when nobody knows the best treatment approach and practically no hospital screens for functional or cognitive capacity - two well known areas of psychiatric disability.  In the outpatient sphere, it is the equivalent of saying that 10 or 20 minutes three or four times a year with an emphasis on medications that are not likely being taken by the patient can possibly affect their real life outcome.

In the case of patients with addictions the treatment is more dire.  When a person using heroin, alcohol, and excessive amounts of benzodiazepines cannot get admitted for detoxification or they cannot get admitted for residential treatment, society and its representative governments at all levels are saying that this is a situation where we can ignore conditions that are clearly life-threatening and in many cases fatal.  We can ignore them because businesses and governments say that this is a collection of disabling and life-threatening diseases that we can ignore so that they can either make money or divert money to treat more socially acceptable life-threatening and disabling diseases.  

This is all a clear pattern of discrimination that not only affects the elderly but anyone with a psychiatric disability or addiction.  If the authors want to do something about that – I say let’s start by reversing over 30 years of discrimination against those with psychiatric and substance use problems that is clearly based on socioeconomics especially the lack of a vocal political constituency, very poor research based on demographic variables rather than complexity, and a lack of innovative research based on poor resource allocation.

George Dawson, MD, DFAPA

References:

1: Boozary AS, Manchin J 3rd, Wicker RF. The Medicare Hospital Readmissions Reduction Program: Time for Reform. JAMA. 2015 Jul 28;314(4):347-8. doi: 10.1001/jama.2015.6507. PubMed PMID: 26219049.

Attribution:

Photo by Mark Buckawicki (Own work) [CC0], via Wikimedia Commons.

Silence on Pro Publica's Recent Big Pharma Payment Disclosures

OK silence as far as psychiatry goes.

For the past ten years we have heard both individual psychiatrists and monolithic psychiatry maligned for accepting Big Pharma cash for presentations, expert consultations, or whatever.  The implications being twofold - that there were no legitimate reasons why a physician seeing patients should be in the employ of a pharmaceutical company and (courtesy of the Institute of Medicine) that since you can't really tell what is a real conflict of interest versus the appearance conflict of interest without some additional leg work that we should just consider any potential conflict of interest an actual conflict of interest.  At that point, the body in the US with the most real conflicts of interest that I can think of (Congress) decided that all payments from pharmaceutical companies and device makers should be catalogued in a data base for everyone to see.  When I accessed the database, it was a clear example of government information technology (IT) at its worst.  There are numerous examples of government IT projects being abandoned as unusable after an investment of hundreds of millions of dollars.  The recent hacks exposing the private information of millions of government employees and millions of classified documents are good examples of the lack of quality in government IT.  Why expect any higher bar with payment disclosures to physicians?

Rather than navigate the unnavigable, a better approach is to look at secondary data sources who have the time and staff required to translate the data like Pro Publica.  On their opening web page there is a small window half way down that asks:  "Has Your Health Professional Received Drug Company Money?"  I plugged in my name as a double check on the system and it returned 27 results with either a first or last name George or a last name Dawson.  None of them was me (which is accurate).  Only one of them was a psychiatrist and that physician had received a total of $88.  The remaining physicians had received anywhere from 0 to $18,450.  I would certainly not be very happy if I was included in this database for receiving zero dollars and wonder how often that mistake is made?

The bar graph of what types of fees were paid by the industry is instructive.  The largest single group of payments were for "Royalty or License" and number of current brand name chemotherapy and antiviral drugs were mentioned.  The next category was "Promotional Speaking".  I can't imagine that rheumatologists, endocrinologists, and cardiologists are not in demand to speak to primary care physicians about the latest developments in their fields.  I have spoken at Primary Care Updates in psychiatry for primary care physicians.  Are those presentations classified as "Promotional Speaking" if a pharmaceutical company sponsors it and the speaker does not mention one of their products by name?  I have similar questions about "Consulting Fee".  If a physician has a specific expertise and is paid by the private company for that expertise, in my opinion they are no different than any other University faculty in similar positions.  The idea that a physician's entire life is encompassed in relationship with patients and that this is somehow a sacred trust is a myth that is perpetrated by concerns who are quite willing to exploit all physicians on that basis.  They are all listed in various places on this blog.

One of their lead stories is A Pharma Payment A Day Keeps Docs’ Finances Okay.  In that article they focus on a neurologist who received $594,363 from 29 different pharmaceutical companies.  They looked at the top rated physician and concluded that she received payments from pharmaceutical companies on 286 days out of the year.  14,600 doctors received payments on at least 100 days per year.  A total of 606,000 doctors received payments, but then again there are people listed in my first search who apparently did not receive any money.  And then there was this excerpt:

"The nation's 3,900 rheumatologists in the data averaged 40 days of interactions with drug and device companies, more than doctors in any other large specialty. They were followed closely by endocrinologists, electrophysiologists and interventional cardiologists...."  In my home state of Minnesota they list the top 20 physicians receiving money from pharmaceutical and device companies and 19/20 are surgeons (orthopedic, spine, eye) and one is a cardiologist.

No psychiatrists?

That is a curious phenomenon considering how frequently psychiatrists are maligned for financial conflicts of interest in the popular media and blogosphere.  No Senate investigations of rheumatologists, endocrinologists, neurologists, or cardiologists?  No attacks on their professional organizations?  No suggestions that their diagnoses, interventions, prescriptions, publications or professional behavior are questionable based on their reimbursement from private industry?  Why is that exactly?  I certainly have plenty of good ideas.

In order to clarify the real picture here, I sent an e-mail to Charles Ornstein, the lead author of the  "A Pharma Payment A Day..." article.  I asked him to post the statistics by specialty including the percentages of physicians getting some payment, per capita payments or by whatever metric they chose.  Considering the scope of payments suggested by these tables, my speculation is that there will be several physicians in the tens of millions of dollars category and that none of them will be psychiatrists.   But I am content to wait to see if he posts those results.   

Until then, don't ever believe that what you read about psychiatrists is a random event free from the usual antipsychiatry biases.

No matter what happens with the Pro Publica data - don't believe that anyway.

George Dawson, MD, DFAPA  

1.  Charles Ornstein and Ryan Grochowski Jones.  A Pharma Payment A Day Keeps Docs’ Finances Okay.  ProPublica Web Site.

Depression and the Genetics Of Large Combinations

from:  CONVERGE consortium.  Nature. 2015 Jul 15. doi: 10.1038/nature14659. [Epub ahead of print] - see complete reference 1 below.         

This is an interesting effort from a large number of researchers looking at candidate genes in major depression. The authors studied major depressive disorder (MDD) in 5,303 Han Chinese women selected for recurrent major depression compared with 5,337 Han Chinese women screened to rule out MDD. The depressed subjects were all recruited from provincial mental health centers and psychiatric departments of general hospitals in China. The controls were recruited from patients undergoing minor surgical procedures in general hospitals or from local community centers. All of the subjects were Han Chinese women between the ages of 30 and 60 with four Han Chinese grandparents. The MDD sample had two episodes of MDD by DSM-IV criteria. The diagnoses were established by computerized assessments conducted by postgrad medical students, junior psychiatrists, or senior nurses trained by the CONVERGE team. The interview was translated into Mandarin. Exclusion criteria included other serious medical of psychiatric morbidity (see details in ref 1). 

Whole genome sequences were acquired from the subjects and 32,781, 340 SNPs were identified, 6,242,619 were included in genome-wide association studies (GWAS). Figure 1 above is the quantile-quantile plot for the GWAS analysis resulting from "a linear mixed model with genetic relatedness matrix (GRM) as a random effect and principle components from eigen-decomposition of the GRM as fixed effect covariates." I won't pretend to know what that methodology is, even after reading the Methods, Supplementary Notes section. I expect that it would take a more detailed explanation and in the era of essentially unlimited online storage capacity, I would like to see somebody post it with examples. Without it, unless you are an expert in this type of analysis you are forced to accept it at face value. I am skeptical of manipulations of data points that provide a hoped for result and can cite any number of problems related to this approach. On the other hand information of this magnitude probably requires a specialized approach. 

In this case the authors found two loci on chromosome 10 that contributed to the risk of MDD. They replicated the findings in an independent sample. 

One of the features that I liked about this paper was the focus on patients with severe depression. I have lost count of the number of papers I have read where the depression rating scores were what I consider to be low to trivial. Many rating systems used in clinics seem to use these same systems for determining who gets an antidepressant and who does not.  Whenever I see that, I am always reminded of the "biological psychiatry versus psychotherapy" debates that existed when I was in training in the 1980s.  Once of my favorite authors at the time was Julien Mendlewicz and anything he would publish in the Journal of Clinical Endocrinology and Metabolism (4-6).  There is a table in one of his studies with the HAM-D scores of the patients with unipolar depression he was seeing that ranged from 30-57 with a mean of 41+/- 10.  For bipolar patients in the same study the range was 30-43 with a mean of 36 +/- 5.  One of those patients could not be rated initially because of severe psychomotor retardation.  These are levels of depression that are not typically seen in depression research from either the standpoint of basic science and probably never for psychopharmacological research.  Much of the research that I am aware of allows for the recruitment of patients with HAM-D scores in the high teens and low 20s.  I don't think that is the best way to run experiments on biologically based depressions or antidepressant medications, but there is rarely any commentary on it.  The CONSORT group in this paper finally comments on this factor as being a useful experimental approach even though Mendlewicz was using it in the 1980s.

The second issue that crops up in the paper is replication.  The authors validate their original work by running a second sample for validation.  That is the approach we would use in analytic chemistry.  If we were using a new technique we would run samples in triplicate or in extreme cases in sets of 5 to make sure we could replicate the analysis.  It reminded of one of the first great genetic marker papers in the field that was published in the New England Journal of Medicine by Elliot Gershon's lab in 1984 (2).  It was an exciting proposition to consider that fibroblasts could be grown from a skin biopsy and the muscarinic cholinergic receptor in those fibroblasts would be a marker for familial affective disorder.   The general observation in this pilot study of 18 patients was that they had an increased muscarinic receptor density in fibroblasts compared to controls and that the relatives with histories of minor depression had receptor densities that were more similar to the subjects with mood disorders than normal controls.  The subjects with familial affective disorder were defined as subjects with bipolar I, bipolar II, or major depression according to Research Diagnostic Criteria (RDC).  No rating of depression severity was made acutely or on a historical basis.  These findings could not be replicated, in the end even by the original lab.  That process played out in the pages of the New England Journal of Medicine (3) and the original findings were withdrawn.  It would be interesting to look at how often a similar debate occurs in a prestigious journal these days.  Estimates of non-replicable findings by the pharmaceutical industry suggests that it should happen a lot more often.   

In terms of the original paper, the sheer amount of information involved in the genetic code is staggering.  Just looking at the 130 millions base pairs on Chromosome 10 and thinking about combinations of 2, 3, 4, 5, or 6 base pairs yields the numbers in the table below entitled "Combinations of 130 million base pairs."  The exponential notation ranges from 10¹⁵ to 10⁴⁵ or a quadrillion  to a quattuordecillion combinations.  Figuring out the best way to determine which combinations are relevant in illnesses with polygenic inheritance will be an interesting process.

  

George Dawson, MD, DFAPA

References:

1:  CONVERGE consortium. Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature. 2015 Jul 15. doi: 10.1038/nature14659. [Epub ahead of print] PubMed PMID: 26176920.

2:  Nadi NS, Nurnberger JI Jr, Gershon ES. Muscarinic cholinergic receptors on skin fibroblasts in familial affective disorder. N Engl J Med. 1984 Jul 26;311(4):225-30. PubMed PMID: 6738616.

3:  Failure to Confirm Muscarinic Receptors on Skin Fibroblasts.  N Engl J Med 1985 Mar 28; 312: 861-862  PubMed PMID: 3974670.

4:  Linkowski P, Mendlewicz J, Kerkhofs M, Leclercq R, Golstein J, Brasseur M,Copinschi G, Van Cauter E. 24-hour profiles of adrenocorticotropin, cortisol, and growth hormone in major depressive illness: effect of antidepressant treatment. J Clin Endocrinol Metab. 1987 Jul;65(1):141-52. PubMed PMID: 3034952.

5:  Linkowski P, Mendlewicz J, Leclercq R, Brasseur M, Hubain P, Golstein J, Copinschi G, Van Cauter E. The 24-hour profile of adrenocorticotropin and cortisol in major depressive illness. J Clin Endocrinol Metab. 1985 Sep;61(3):429-38. PubMed PMID: 2991318.

6:  Mendlewicz J, Linkowski P, Kerkhofs M, Desmedt D, Golstein J, Copinschi G, Van Cauter E. Diurnal hypersecretion of growth hormone in depression. J Clin Endocrinol Metab. 1985 Mar;60(3):505-12. PubMed PMID: 4038712.


Attribution:

Extended Data Figure 1 is from: CONVERGE consortium. Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature. 2015 Jul 15.  With Permission from Nature Publishing Group  © 2015.  License number 3672900044284.

Supplementary 1:

Addiction and ADHD - The Bullet Points

Figure 1.  from Shaw M, Hodgkins P, Caci H, et al. A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and non-treatment.  BMC Med. 2012 Sep 4 10:99 (see ref 6 below).

One of the main concerns in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) is whether treatment improves outcomes.  The outcomes measure of interest may depend on the clinical population that you are focused on treating.   In primary care settings, my impression is that a lot of the adults treated by internists are relatively stable and that they do not have a lot of problems with other mental illnesses or addictions.  That is my speculation based on some of the numbers of adults I have heard are seeing primary care physicians and the fact that seeing those numbers with even a fraction of patients who have additional psychiatric problems or addictions would be unsustainable.  I have also directly observed the pattern that many patients who are discharged from primary care for stimulant overuse or psychiatric complications like mania end up seeing psychiatrists.  As a psychiatrist working in a residential setting that treats substance use problems - trends in overprescribing, misdiagnosis and confusion about the concept of addiction and ADHD treatment are readily observed.  It is very clear that people with clear ADHD can misuse stimulants and continue to insist on using stimulants.  It is clear than many of these people develop insight into this and can say at one point that they can no longer take stimulants even though they have a bona fide ADHD diagnosis.  It is also clear that there is a lot of confusion among treating professionals about the issue of whether or not a stimulant should be prescribed to a person with an addiction.  

There is a lot of overlap between the diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder and addiction or substance use disorders.  Discovering this overlap depends on clinical experience, training and exposure to patients with addictions.  It is fairly common to read studies about ADHD outcomes that may not look at addictions as outcomes.  Like many areas in medicine, some of the early studies in this area have not been borne out by subsequent studies.  The study of this problem has only been a relatively recent endeavor.   The original AHRQ report in 1999 (1) looked at 77 randomized controlled clinical trials included in the time period from 1971 to 1999.  Half of the studies were published since 1990.  At that time there were only 13 adult studies.  The outcome variables were generally improvement on symptomatic rating scales, neuropsychological tests or educational achievement tests.    

Connor's review (2) looks at the studies prior to 2006.  At the time he states that there were a total of 14 studies that looked at potential abuse issues.  One of the studies supported the idea of behavioral sensitization or stimulant administration leading to craving and eventual self administration.   That study did not control for Conduct Disorder, a comorbid condition  that increase the risk of substance use disorders.  The other studies found no increased risk, and in some cases a decreased risk of substance use disorders.  There were no review elements that looked at addictions or substance use disorders.  A meta-analysis of 6 studies by Wilens, et al showed a 1.9 fold reduction in risk in the stimulant treated patients.  Connor's conclusion is that "...in uncontrolled environments, active substance abuse is a relative contraindication to prescribing stimulant medications."  the use of atomoxetine or antidepressants with a known efficacy for ADHD was encouraged (p. 626).

A more recent review by Shaw, et al from 2012 takes a different approach.  The authors looked at studies between 1980 and 2010 with a minimum follow-up period of two years or more (prospective or retrospective) or cross sectional studies that compared two ages differing by two years of more.  Nine separate outcome measures were examined as indicated in Figure 1 at the top of this page.  Since some studies reported more than one outcome measure, a total of 636 outcomes were examined from the 351 studies reviewed for this paper.  Drug use or addictive behavior was one of the most frequently examined outcomes with a total of 160 results.  The next most frequent result was academic functioning with 119 results.  The data is represented as percentage comparisons as improved, similar, or poorer than the comparators.  As an example in Figure 1, the last 4 categories show that treatment was beneficial in 67% of the drug/addictive, 50% of the antisocial, 50% of the service use outcomes, and 33% of the occupational outcomes.  The authors conclude that in these four treatment groups there was no benefit conferred by treatment.  They looked at the issue of treatment of these four groups in the rest of the world and found that there was substantially better outcomes for this subgroup.  There were significant methodological problems noted in the studies including the need to control for Conduct Disorder, Oppositional Defiant Disorder, and a number of other comorbid psychiatric disorders.  Other potential comparison issues between the American and non-American studies included the fact that the American studies were largely prospective, the non-American studies used more stringent ICD-10 codes.  One of the main variables that addiction psychiatrists are focused on clinically is when the addiction is established.  Did it occur before, during, of after the ADHD diagnosis in childhood?  What does that spectrum suggest for the impact of stimulant treatment on an addiction outcome?

Where does all of this leave clinicians today?  It is possible to find clinicians who believe that they are treating addiction with stimulants because they are reducing impulsivity associated with ADHD.  There are also clinicians who believe that stimulants must be avoided at all costs, even in people with a diagnosis of ADHD.  Is there a rational approach to discuss what is known about the diagnosis and treatment with the patient as part of their overall treatment program that might optimize treatment outcomes?  I think that there is and have written it down in this worksheet entitled 28 Discussion Points for Stimulant Treatment of ADHD.  The worksheet is intended to address problematic diagnosis as the first point of variance.  It discusses the relevant addiction and safety considerations.  There is also a framework for exploring the decision to use a stimulant in the broader context of a treatment plan that may include non-medical therapists and treatment programs and housing programs that may limit or prohibit the patient from using stimulants.  It does not incorporate the therapeutic alliance and overprescribing considerations.  One of the most difficult tasks for physicians is not prescribing a medication with addictive potential when a person believes it is necessary for their life or they are demanding it.

Remembering that people with addictions are compelled to take stimulants whether they improve outcomes or not is an important part of providing quality care to this population.
 

George Dawson, MD, DFAPA



References:

1:  Jadad AR, Boyle M, Cunningham C, et al.  Treatment of Attention-Deficit/Hyperactivity Disorder.  Evidence Report/Technology Assessment No. 11 (Prepared by McMaster University under Contract No. 290-97-0017).  AHRQ Publication No. 00-E005.  Rockville, MD:  Agency for Healthcare Research and Quality.  November 1999.

2:  Connor DF.  Stimulants.  In: Barkley DF.  Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment.  3rd ed.  New York, NY.  The Guilford Press, 2006: 608-647.

3:  Barkley RA, Fischer M, Smallish L, Fletcher K. Does the treatment of attention deficit/hyperactivity disorder with stimulants contribute to drug use/abuse? A 13-year prospective study. Pediatrics. 2003 Jan;111(1):97-109. PubMed PMID: 12509561.

4:  Wilens TE, Faraone SV, Biederman J, Gunawardene S.  Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics. 2003 Jan;111(1):179-85. PubMed PMID: 12509574.

5: Biederman J, Monuteaux MC, Spencer T, Wilens TE, Macpherson HA, Faraone SV. Stimulant therapy and risk for subsequent substance use disorders in male adults with ADHD: a naturalistic controlled 10-year follow-up study. Am J Psychiatry. 2008 May;165(5):597-603. doi: 10.1176/appi.ajp.2007.07091486. Epub 2008 Mar 3. PubMed PMID: 18316421.

6:  Shaw M, Hodgkins P, Caci H, Young S, Kahle J, Woods AG, Arnold LE. A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and non-treatment. BMC Med. 2012 Sep 4;10:99. doi: 10.1186/1741-7015-10-99. Review. PubMed PMID: 22947230.  online at: http://www.biomedcentral.com/1741-7015/10/99


Attribution:

The graphic at the top of this post is from reference 6 above and is posted per the open access license at that site.

Placebo - Nocebo Implications For Psychiatric Research and Clinical Care

The words popped up this week in two separate journals that I read regularly.  In the New England Journal of Medicine, there was an opinion piece on Placebo Effects in Medicine.   In the Journal of Clinical Psychiatry there was an article on Nocebo Effects in the Treatment of Major Depression.  Most people are familiar with the definition of placebo, or an apparent therapeutic effect from an otherwise inert medication or therapeutic intervention.  Even though the nocebo effect has been known for some time, it is less familiar.  A nocebo effect is an apparent adverse reaction to an inert substance.  I first became aware of it about 30 years ago as a clinical investigator working on a double blind placebo controlled study of an experimental anxiolytic medication.  In that study, the blind could be broken and the research subject informed of whether they were receiving active drug or placebo.  I had to inform several distressed subjects that they were receiving placebo after they insisted on stopping the study due to medication side effects.  In clinical practice, nocebo effects are also apparent typically as adverse reactions to low doses of medication or very atypical responses to medication.  In clinical practice, the determination is always probabilistic because placebos can't be given.

In the nocebo paper (1),  the authors analyze treatment-emergent adverse events (TEAEs) in 1,565 or 2,457 placebo treated participants in 20 industry sponsored, randomized, placebo controlled trials of duloxetine.  There were 16 different study designs typically in terms of length.  The Hamilton Depression Rating Scale (HDRS) was the primary outcome measure in 17 of the trials.  The authors looked at worsening ratings of depression score,  TEAEs, and discontinuation rates.  The authors hypothesized that prior conditioning by previous treatments (especially within the same class of drug) and negative expectations regarding treatment might predict nocebo responses.  They could find no  results to support either of these theories.  

The nocebo response has clear implications for interpreting the results of clinical trials in psychiatry and clinical practice.  Nocebo has really not been a term in the discussion, even by some authors who have basically declared that there is no antidepressant response (3).  Practically all of the naysayers doing meta-analyses to prove that antidepressants don't work don't include any discussion of it in their work.  All that you hear is that there is really no difference or not much difference between active drug and placebo.  What if 10% of the worsening depressive symptoms and 5% of the dropouts were due to a nocebo response?  That is a significant proportion of the trial subjects carried forward in an intent-to-treat design.

Should nocebo response rates be calculated for all clinical trials?  I think that they should and that data should be collected in a standardized manner as a part of clinical trials redesign in psychiatry.

What happens in clinical practice?  If a patient tells me that he or she is cutting up the lowest dose of a medication into sixteenths and can only tolerate 1/16 at a time due to side effects, I am not going to tell them to gradually titrate the dose up by sixteenths.  I know that this is probably a nocebo response, and it will likely occur with other medications.  I tell them to stop whatever they are doing immediately and we will try something else.  That could be a treatment focus on insomnia, supportive psychotherapy, exercise, meditation, relaxation techniques, mindfulness approaches -  anything but that medication.  If a patient tells me that they are basically "allergic to everything" my approach is the same.  I have no interest in prescribing a medication that makes a patient feel worse, irrespective of the purported clinical phenomenon.  Often, the patient's response is surprise.  Many people with these reactions are accustomed to physicians anguishing with them over the fact that they "cannot take any medication" and going through all of the excruciating misadventures associated with that nocebo response.  I certainly don't.  There are many other approaches and many other doctors who they can see.  One of the behaviors that I have observed in this population is a tendency to seek out complementary medicine providers where there is a risk that nocebo responders will find other treatments that may be more expensive with no proven efficacy in the context of improved tolerability.  There is also a tendency for non-psychiatrists to "kick the can down the road" and tell the patient experiencing a nocebo response that they have a psychiatric problem and need to see a psychiatrist.  I think it is useful to discuss the placebo and nocebo effects with patients and provide them with as much detail as possible.  I tend to focus on what is known rather than speculative neurobiology, especially in any conversation about endorphins.  Endorphins have already been excessively hyped as being associated with the "high" associated with exercise but the evidence is weak (4).

The opinion piece on placebo effects (2) is an interesting contrast.  One of the authors of this piece is associated with the Program in Placebo Studies & Therapeutic Encounter (PiPS).  A white paper on their web site describes their observations about the placebo effect and an action plan to conduct further research and a possible introduction of it as an action plan in medicine.  In the opening paragraphs they allude to the theoretical neurobiology of placebo effects including the early genetics of placebo responders.  They summarize three major findings of current research on placebo effects.  The first is that they are not curative.  The best example of this was the placebo effects with asthmatics.  Their subjective symptoms are relieved but their forced expiratory volume in one second (FEV_1.0) - stays the same.  The same is true of placebo in cancer treatment where the side effects of treatment improve but there are no changes in tumor size.  The second is the expectation effect, best illustrated by an example the authors give having to do with rizatriptan - a standard migraine medication.  If the active drug is labeled "placebo" the results are no better than placebo.  If the active drug is correctly labeled the antimigraine effect increases by 50%.  They list a number of medications with similar expectation effects.  Lastly, they touch on the nocebo effect as "the psychosocial factors that promote therapeutic placebo effects also have the potential to cause adverse consequences."  In a clinical trial of finasteride for benign prostatic hypertrophy, patients informed of sexual side effects report them at three times the rate of men who have not been informed.  They quote the statistic that 4-26% of placebo treated patients in clinical trials discontinue the study due to perceived side effects.  The philosophical aspects of this commentary are probably the most interesting.  The authors correctly point out that the placebo effect has pejorative connotations.  There is perhaps no better example than in psychiatry.  They suggest a further understanding and application of the various facets of this response to create a better therapeutic alliance with patients and alleviate their suffering.

This is a fascinating area of psychiatry.   I am generally compulsive about informed consent in general and more so in high risk situations.  For the highest risk warnings that I give patients - serotonin syndrome, tardive dyskinesia, agranulocytosis, cardiovascular complications, seizures, renal failure, and liver failure - I have never seen a nocebo effect.  That may have to do with the clear objective markers of these problems or the fact that I describe them as rare complications.  On the issue of sexual side effects, I clearly explain what they are and give people the exact numbers from clinical trials.  When it comes to explanations about medication side effects, the one that leads to the most problems is increased appetite and weight gain.  Even though that side effect is common with medications that psychiatrists prescribe, people tend to flee from it independent of the statistics and how much weight they have recently lost or gained due to either the primary psychiatric diagnosis or substance use.  It seems that most people who are likely to be nocebo responders, are well known before it gets to the informed consent stage.  In the initial evaluation stages they have clear histories of not be able to tolerate much of anything and the side effects described are very atypical.  

Another area where placebo-nocebo comes into play is when the primary disorder has been treated and a patient presents with the idea that the "medication has lost its effect".  There are papers written on this effect and some give statistics about how often it occurs.  In my experience, these outcomes are most often not due to a medication, but prevailing psychosocial factors and/or substance use.  Clarifying and addressing those issues frequently leads to better outcomes than changing medications or adding another one.  In many way it seems that some elements of a placebo response are an antidote to psychosocial stressors that affect medication responses.

Translating life into a medication mediated process needs to be averted at all costs.  




George Dawson, MD, DFAPA


References:

1:  Dodd S, Schacht A, Kelin K, Dueñas H, Reed VA, Williams LJ, Quirk FH, MalhiGS, Berk M. Nocebo effects in the treatment of major depression: results from an individual study participant-level meta-analysis of the placebo arm of duloxetine clinical trials. J Clin Psychiatry. 2015 Jun;76(6):702-11. doi: 10.4088/JCP.13r08858. PubMed PMID: 26132671.

2:  Kaptchuk TJ, Miller FG. Placebo Effects in Medicine. N Engl J Med. 2015 Jul 2;373(1):8-9. doi: 10.1056/NEJMp1504023. PubMed PMID: 26132938.

3:  Ioannidis JP. Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials?  Philos Ethics Humanit Med. 2008 May 27;3:14. doi: 10.1186/1747-5341-3-14. PubMed PMID: 18505564.

4: Harbach H, Hell K, Gramsch C, Katz N, Hempelmann G, Teschemacher H.Beta-endorphin (1-31) in the plasma of male volunteers undergoing physical exercise. Psychoneuroendocrinology. 2000 Aug;25(6):551-62. PubMed PMID: 10840168.


Attribution:

The graphic in this case is from 2,000 Plus Royalty Free Images from the Apple App store.

Lancet Psychiatry's Inconsistent Look At Conflict Of Interest

The opening paragraphs of this editorial piece seemed promising, especially these lines:

It's not just about the money. In mental health, reputational interests exist alongside potential financial conflicts. There might also be deep-rooted interests based on professional identity. Our specialty sometimes resembles a field of conflict, or maybe some particularly ill-tempered football league—psychiatrists versus psychiatrists, psychiatrists versus psychologists, behavioural psychologists versus psychoanalysts, pill pushers versus therapists, and, as a forthcoming attraction, ICD versus DSM—a world of factionalism, rifts, ideology, personal philosophy, and ego (or should that be id?). (ref 1)

Unfortunately things rapidly fell apart after that point.  The above statements capture much of the position I have advocated on this blog from day one.  Anyone who is not aware of the purely political factors affecting some of the conflicts outlined in these sentences is extremely naive.  If anyone needs a more extensive scorecard, please refer to the graphic at this link.  On the other hand, the problem may be that I have a restrictive view of what the authors here refer to as "our specialty".  They seem to include a lot of other people than just psychiatrists.  Midwestern psychiatry may be a different culture than the rest of psychiatry.  I think we tend to view ourselves as physicians first and then psychiatrists.  We may be more comfortable talking with medical and surgical colleagues and medical knowledge is valued rather than denigrated.  We don't claim medical knowledge for the political advantage of seeming to be like other doctors.  We know a lot of medicine because we treat a lot of people with psychiatric and medical problems and consult in acute care settings.  Some of the conferences I see advertised and a few I have attended suggest to me that there are psychiatrists out there who do not have that interest in all things medical and neurological and may be more comfortable talking with non-physicians.   When I think about "our specialty",  I am thinking about those hundreds of medically oriented psychiatrists who I know who want to talk about taking care of people with severe illnesses.  People who are comfortable in hospitals and medical clinics.  People who know about the brain, labs, brain imaging, EEGs, and all things medical.

You might think that this is just another "faction" of a fractionated specialty, but it has been surprisingly seamless to me.  I trained in three major University settings in their core hospitals and affiliated Veteran's Hospitals.   When I got out, I practiced in community hospitals and clinics before coming back to a University affiliated tertiary care center.  The knowledge base of what needed to be diagnosed and treated was uniform across all of those settings.  I could expect highly competent psychiatrists available in those settings to consult with and for cross coverage.  The focus was always excellent clinical care and avoiding mistakes.  It did not resemble the confederacy of dunces described in this editorial and frequently in the popular press.  The practical issue is that practicing in acute care settings focuses the type of care that needs to be delivered.  People need to get better, and they need to get better in a hurry.   All of the debates wash out in the bright light of pragmatism.  If your plan cannot be enacted and result in clear improvements, you don't last long in that environment.  The potential complications alone will make you look bad.  The results of a clinical trial of a medication in completely healthy adults is irrelevant.

Turning the management of the world's most expensive health care system over to a for-profit industry capable of skimming hundreds of billions of dollars off the top for what amounts to a rationing scheme is a uniquely American solution, so I would not expect a lot of recognition in a British journal.  Medical journals make it seem like we are all practicing the same brand of medicine independent of cultural and political constraints.  I doubt that the editors in these situations will prove any more savvy than American editors who seem to ignore the fact that, managed care and everything that involves dwarfs the pharmaceutical industry in terms of conflicts of interest affecting the care of patients at least in the United States and that pro-managed care articles deserve at least as much scrutiny as papers written about pharmaceuticals.

The authors use about 1/3 of their space to criticize Rosenbaum's New England Journal of Medicine series on conflict of interest and the term pharmascolds.  They get one point correct, good research should not be ignored irrespective of who is funding it.  Like other critics of Rosenbaum, they wax rhetorical in their criticism and side step the numerous valid points that she makes.  They suggest that they should be focusing on a larger number of conflicts of interests ranging from the potential financial gains from various non-pharmacological innovations to "professional vendettas" but provide very little insight into how that might occur other than continuing to "question, query, probe, and interrogate" beyond the usual financial conflict disclosure.

On that procedure, I will say good luck to them and editors everywhere.  The Institute of Medicine inspired approach (2) of considering the appearance of conflict of interest and conflict of interest to be equivalent and unevenly applying that to one industry while completely ignoring the insidious effects of another has done very little to  "strike the right balance between addressing egregious cases and creating burdens that stifle relationships that advance the goals of professionalism and generate knowledge to benefit society."

There is no better example than a health care system that systematically discriminates against mental illness and addiction and does that on the basis of questionable research based on business rather than scientific principles.  The editors could start to expand their probing to spreadsheet research that looks at the purported "cost effectiveness" of managed care or collaborative care and question any associated reported quality measures.  It is always amazing how new research compares a relatively trivial case management intervention to "care as usual", when that terrible care was the product of early research on how care can be rationed.   A good starting point might be a requirement analogous to "refusing to publish non-research articles on depression from authors who have received unrelated funding from pharmaceutical companies that market antidepressant." by refusing to publish opinion pieces from opinion leaders in the business of rationing mental health services.  Refusing to publish research articles that compare rationed to less slightly rationed care would be another.

If medical research is really supposed to be generating knowledge that benefits society, where are the state-of-the-art models for psychiatric care that can set this standard?  That is what editors everywhere should be looking for.  

George Dawson, MD, DFAPA

Ref:

1:  Conflict Resolution.  The Lancet Psychiatry 2015, Volume 2, No. 7, p571, July 2015

2:  IOM (Institute of Medicine). 2009. Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: The National Academies Press.