Treatment of chronic pain with opioids - back to the future

I thought I would wade in on this issue largely because I am not hearing a lot of rational discussion about the problem.  You might ask: "What does a psychiatrist know about this issue?" and the answer like most questions about psychiatry is "plenty".  I worked on a busy inpatient unit for 22 years and saw plenty of people with with severe chronic pain and episodic pain crises.  In that same facility, I also covered consults on medical and surgical patients many having problems with chronic pain and addiction.  As an addiction psychiatrist, I have talked with countless people who ran into problems with pain medications or relapsed to using another drug after being exposed to opiates for treatment of acute or chronic pain.  There seems to be very little reality based information out there to inform people about the risks and benefits of pain treatment with opiate medication.  The argument like most in our society is politically polarized to those who believe it is unconscionable to not treat pain even if it means a long course of opioids to those who believe that opioids are dangerous medications that should be conservatively prescribed.  So where does the truth lie?

I can tell you how it was in Minnesota in the 1990's.  There were very few pain specialists.  The wide spread prescription of opiate medications for chronic noncancer pain by generalists was uncommon.  In many cases if it seemed indicated, the generalist would refer their patient to a pain specialist who would provide them with a letter of agreement on the use of chronic opioids.  That all changed with a Joint Commission initiative on pain in 2000.  At least some authors see it that way and that was my experience.  Since then opioid prescriptions have been taking off with an associated increase in the production of these compounds.  This graphic from the CDC is instructive (click to enlarge).  The rates of increase of sales, deaths, and treatment admissions are all increasing at an astronomical rate relative to population growth.

The issue that is debated in the media and some government web sites is why is this happening and what is the best way to deal with it.  The FDA has recently incentivized drug manufacturers to come up with better tamper proof opioids.  The enforcement arm of the government is rigorously prosecuting some doctors.  The FDA has also initiated a course for doctors who prescribe opioids.  None of these measures addresses the core problems that were successfully addressed in Minnesota in the 1990s.  I will take a look at the specific issues involved:

1.  The genetics of opioid preference:   People at risk for abuse and addiction to opioids have intensely positive subjective experiences from taking opioids.  People not at risk have intensely negative experiences or the opioids make them physically ill.  We currently know nothing about the genetics of this response, but it makes sense to let patients know that if they do have an intensely positive response in terms of feeling euphoric or energetic that is not a good sign in terms of addiction potential.  It might even be reasonable to come up with a plan about what to do if that happens.  Seeing people back in a month who have no knowledge of this risk is probably not the best plan.  It is critical that there is a good therapeutic alliance between the patient and physician and that they are both focused on the full spectrum of problems.  

2.  The genetics of opioid response:  Individuals studies and reviews of studies generally show that a subset of patients respond to opioids.  There may be additional factors that should factor into patient selection such as the specific type of neuropathic pain.  The current concern and reaction to the opioid epidemic is based on the concept that opioid prescribing is a potentially high risk intervention.  If that is the case we need a better options for patient selection than a subjective report of pain.

3.  The public perception that opioids are the silver bullet of pain relief must be dispelled: This is the driving force behind escalating doses of opioids and the addition of benzodiazepines (an equally bad idea).  Excellent double blind placebo controlled studies of self titrated opioids in chronic neuropathic pain have showed moderate pain relief that is on par with non-opioid medication.

4.  Tolerance to analgesia and opioid induced hyperalgesia:  Education about these phenomena is needed because both lead to escalating doses of opioids.  The dose escalation may be appropriate, but in many cases the dose is increased with the goal of eradicating pain and that is an unrealistic goal.  In people who have analgesic induced hyperalgesia, they are often shocked that their pain improves with discontinuation of the opioids.

5.  Assessment of functional capacity is critical:  Functional capacity is the ability to function in daily life.  It must be carefully assessed in anyone who is on chronic opioid therapy.  At moderate doses and in combination with other pain medications opioids can impair coordination, cause excessive sedation, and lead to significant impairment in daily functioning.  This is a sign that the dose of the opioid may be too high and reducing the dose is indicated.

6.  A hierarchical approach to pain treatment is still necessary and is the most rational approach to reducing the current epidemic of excessive opioid prescriptions:  If the degree of pain relief across a population is the same, why not use the drug with the lowest abuse and overdose potential?  That was the default model in the 1990s in Minnesota.  The National Health Service in the United Kingdom has operationalized that as their current pathway for treating neuropathic pain in the algorithm below (click to enlarge).  Note that the medications with no abuse potential are at the entry levels in this diagram and that pain specialists are the gatekeepers for opioids.

  
Like most political debates the current debate about how to stop the epidemic of opioid overdoses ignores that fact that the problem may have originated with a political initiative in the first place.  Using the NICE algorithm to get us back to the Minnesota practice model of the 1990s is a logical solution.

George Dawson, MD, DFAPA


Rowbotham MC, Twilling L, Davies PS, Reisner L, Taylor K, Mohr D. Oral opioid therapy for chronic peripheral and central neuropathic pain. N Engl J Med. 2003 Mar 27;348(13):1223-32. PubMed PMID: 12660386.

National Institute for Health and Clinical Excellence. Neuropathic pain: the pharmacological management of neuropathic pain in adults in non-specialist settings. NHS. March 2010.

Supplementary 1:

The Care Pathway Graphic is copyrighted © National Institute for Health and Care Excellence (2010) and is posted based on their allowance for reproduction for educational and not-for-profit purposes.  See their updated and revised guideline at: http://www.nice.org.uk/nicemedia/live/14301/65782/65782.pdf

"Anything worth winning is worth cheating for."

I used to speedskate in pack style races.  For a while one of my competitors would come to the line and make that statement just before we all took off.  Most of us thought that it was hilarious.  One day I was intentionally sandbagging, and told several people that I was really fatigued and did not anticipate that I would be very competitive.  When the gun went off I broke for the first turn as fast as everyone else.  They gave me a hard time for sandbagging after that race and I reminded them: "Anything worth winning is worth cheating for."

That brings me to the recent Lance Armstrong saga.  The Oprah interview followed by endless opinion pieces and man on the street interviews focused on the emotional response to his doping confessions.  That has continued this week with a skewering by comedians, indignant responses by journalists, endless analyses of his interviews, the looming threat of ongoing legal action, and the expected outrage from the process of being lied to.  But I wonder if there is not a lot more going on that just cheating and lying. 

A little context is important.  Bicycle racing has been associated with cheating for decades.  Most people don't realize it but one of the most widely used antipsychotics,  haloperidol was invented as an antidote to amphetamines by Paul Janssen in response to the following observation he made in the 1950s:

“Even when he was pulled off his bike and congratulated by a reporter, he tried to continue cycling” Janssen said. It was obvious, he added, that “finding a treatment for amphetamine intoxication would provide a cure for paranoid schizophrenia”.  Ivan Oransky.  The Lancet - 17 January 2004 ( Vol. 363, Issue 9404, Page 251 )

Haloperidol was invented in 1959.  A British cyclist allegedly under the influence of amphetamines died in 1967 during the Tour de France while ascending Mt. Ventoux.

Over the intervening decades doping has become more sophisticated and the anti-doping authorities have become more sophisticated.  Epo was probably introduced to cycling as early as the 1980s.  There were 18 deaths of young professional cyclists in the late 1980s and 8 additional deaths since 1993.  The commonest compounds in the news that are thought to give a competitive advantage include testosterone and testosterone derivatives and the cytokine - erythropoietin or Epo for short.  Erythropoietin the primary regulator of human red blood cell production, survival, and differentiation of bone marrow derived blood cells.  It has been known for some time that is also has potential performance enhancing characteristics in elite athletes:

“Administration of Epo, by increasing haemoglobin and haematocrit, increases the oxygen carrying capacity of the blood, thereby improving the athlete’s endurance.  The use of Epo in this manner can be dangerous, increasing the risk of heart failure, strokes and thrombosis.  A number of high profile cases have been reported in the press, including in 1998, the arrest on drugs charges of the doctors of the Tour de France cycling Team, Festina.   One of the Festina riders ……has only recently returned to competition after a ban after admitting to regularly taking Epo.”  The Cytokine Handbook. Volume 2, p 1267.

Testosterone and its derivatives referred to as anabolic steroids first appeared in 1954. The use of anabolic steroids or anabolic androgenic steroids (AAS) has increased significantly across the population over the past 20 years.  In the 1990s about 1% of high school students used these compounds.  This increased to 3% recently with as many as 10% of 15-19 year old boys (4).  Pope, et al (5) reviewed the evidence that AAS use resulted in addiction and came up with a figure of 30% across seven studies with the qualifier that selection bias may be a factor.  The most recent review of the evidence (6,7) indicates that AAS are widely abused and that most AAS users are engaged in polypharmacy.

The actual effects of performance enhancing drugs are very difficult to evaluate largely because of the secrecy surrounding their use and the inability to investigate them on an systematic basis.  As I hear stories about what has been used a lot of it does not seem to make any sense.  For example, there was the famous incident where a Tour de France cyclist tested positive for testosterone after gaining 4 minutes on the field.  In the subsequent discussion he said initially that alcohol may have been the reason but eventually acknowledged using a testosterone patch.  The stage occurred well into the race and it made no sense to me why he thought that testosterone would be effective overnight.  An alternative explanation is that he was using more testosterone and the testing done was not accurate .  I have also heard recent comments on taking “hydrocortisone pills.”  I don’t understand how anyone would expect a glucocorticoid to lead to performance enhancing effects when it has a catabolic effect on muscle tissue.  There is some more clear cut documentation showing potential performance advantages from anabolic steroids, but much of it is anecdotal with little attention paid to minimum doses.  In fact some of the literature describes a natural tendency for escalation and uncontrolled use – a hallmark of addiction.  The literature on AAS use and whether or not they do enhance performance is varied.  The original literature originated in secret classified documents from the German Democratic Republic (GDR) and their Olympic efforts from 1966 through the late 1980s.  In over 150 documents, specific programs and dosing regimens were noted on thousands of athletes and hundreds of physicians and scientists.  An observation of the performance enhancing effects from this paper: 

“Performances could be improved with the support of these drugs within 4 years as follows: Shot-put (men) 2.5-4 m,  Shot-put (women) 4.5-5 m, Discuss throw (men) 10-12 m. Discuss throw (women)11-20m, Hammer throw 6-10 m, Javelin throw(women) 8-15 m, 400 m (women) 7-10 sec, 800 m (women) 5-10 sec, 1500 m (women) 7-10 sec….”

Without access to the original documents it is difficult to say exactly how carefully this was studied but I doubt that it was an A-B-A design with comparisons to placebo.  Nonetheless, if all of the performance enhancement was due to AAS, it would provide a clear advantage in events decided by meters or seconds and could potentially move an athlete from very good to world class.  Subsequent controlled studies like the first study (8) of the anabolic effects of supraphysiological doses of testosterone documented increases in both muscle diameter and strength during the administration of 10 weeks of testosterone injections.  They also commented that the widespread use of AAS at the time (1996) was unsubstantiated.  The authors documented strength increases of 22 – 38% during that experiment.

Another interesting document (3) of the widespread use of AAS by athletes and people interested in the body building aspects of these drugs was based on a hearing on the matter where doctors prescribing steroids were questioned.  The initial focus of this article was the 1988 disqualification of Ben Johnson after he won the 100 m event in the Olympics in Seoul, South Korea.  The physician in that case described a 5 year program of AAS use.  An estimated 20% of AAS were prescribed by physicians and one of the physicians in the report estimated that the size of his practice was 2000 patients and he thought there were 70 other physicians in the Los Angeles area prescribing these drugs.  At the time AAS use in international track and field competition and a “drug free athlete was considered a losing athlete.”

The politics and limited memory of the scope of this problem is also interesting.  Armstrong responded to the rhetoric of the officials who went after him and described his doping operation as the largest and most sophisticated.  A cycling team would not seem large compared with estimates of one million AAS users in the 1990s, 300 thousand of them active in any given year.  From previous estimates that number may be three times as large right now and chances are that many of these people are also using growth hormone and other polypharmaceutical approaches that they believe will enhance their performance.

The bottom line for me is that Lance Armstrong used performance enhancing drugs by his own admission.  Like practically all users of these drugs he lied about using them.  He used the legal system and his resources to his advantage to defend his positions.  None of this is very surprising given a culture that has used performance enhancing drugs for decades and one that is expanding to the use of cognitive enhancers (9).  So be irate with him if you want, but there is clearly a large segment of the population that practices performance enhancement and the population is also expanding into enhancers for intellectual performance as well as athletic performance.  It is not likely that either of these practices will be going away any time soon.

 

George Dawson, MD, DFAPA

1.  Lewis JL, Lotze GM (2003) Haemopoietic cytokines. In: The Cytokine Handbook, vol. 2 (Thompson AW, L. M., ed), p 1267 London: Academic Press.

2.  Franke WW, Berendonk B. Hormonal doping and androgenization of athletes: a secret program of the German Democratic Republic government. Clin Chem 1997;43:1262-1279.

3.  Breo DL.  Of MDs and muscles--lessons from two 'retired steroid doctors'. JAMA. 1990 Mar 23-30;263(12):1697, 1699, 1703-5. PubMed PMID: 2407878.

4.  Lukas SE. (2009) The pharmacology of anabolic steroids.  In:  Principles of Addiction Medicine, Fourth Edition, p 252, Philadelphia: Lippincott, Williams, and Wilkins.

5.  Kanayama G, Brower KJ, Wood RI, Hudson JI, Pope HG Jr. Treatment of anabolic-androgenic steroid dependence: Emerging evidence and its implications.  Drug Alcohol Depend. 2010 Jun 1;109(1-3).

6.  Kersey RD, Elliot DL, Goldberg L, Kanayama G, Leone JE, Pavlovich M, Pope HG Jr. National Athletic Trainers' Association position statement: anabolic-androgenic steroids. J Athl Train. 2012 Sep-Oct;47(5):567-88.

7.  Kanayama G, Pope HG Jr. Illicit use of androgens and other hormones: recent advances. Curr Opin Endocrinol Diabetes Obes. 2012 Jun;19(3):211-9.

8.  Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996 Jul 4;335(1):1-7.

9.  Greely H, Sahakian B, Harris J, Kessler RC, Gazzaniga M, Campbell P, Farah MJ. Towards responsible use of cognitive-enhancing drugs by the healthy. Nature. 2008 Dec 11;456(7223):702-5.

No applause from me

The APA came out with a press release today in response to President Obama's initiative to reduce gun violence and prevent future mass shootings.  Although the release "applauds" these proposals they seem to be short on the mental health side. From the APA release:

“ We are heartened that the Administration plans to finalize rules governing mental health parity under the 2008 Mental Health Parity and Addiction Equity Act, the Affordable Care Act, and Medicaid. We strongly urge the Administration to close loopholes involving so-called ‘non-quantitative treatment limits’ and to ensure that health plans deliver a full scope of mental health services in order to comply with the law. Such action will best ensure that Americans get the full range of mental health services we believe they are intended to receive under federal law.”

So I guess the APA is applauding the initiative but encouraging the closing of loopholes. Call me a skeptic but 20 years of rationing mental health services and cutting them to the bone through managed care intermediaries and aggregating those managed care intermediaries into accountable care organizations does not bode well for the "full range of mental health services". The APA seems to have the naïve position that you can support managed care tactics and provide increased access to quality mental health services.

The next point in the APA release supports school screening and enhanced mental health services in schools for both violence prevention and to identify children at risk or in need of current mental health services. Those are certainly laudable goals but there is minimal evidence that screening is effective. There is also the problem of a lack of infrastructure.  Twenty years of rationing and restricting access to psychiatric services has resulted in long waiting lists or completely unavailable services. If you talk with a child psychiatrist, they will tell you that the current system is set up to offer medications in place of a more comprehensive approach to psychiatric treatment. At the social services level, residential treatment for children with severe problems is practically nonexistent. As a recent example, I was informed last week of a school social worker who could not get a child assessed for admission to an adolescent psychiatric unit and when that was not possible could not get an appointment to see a psychiatrist in a major metropolitan area. Screening for problems does not make any sense unless there is an infrastructure available to address those problems when they are found.

The final point in the APA release addresses the issue of physicians being able to discuss firearms at home with their patients. This has been a standard intervention for physicians ever since I have been practicing and it is always part of an assessment for suicide and homicide risk. There was a state initiative last year making it illegal for physicians to discuss firearms in the home with their patients. Part of the rationale for that law was that it could result in firearm owners being identified and placed them at theoretical risk for their firearms to be confiscated by the state.  I can say from experience that my discussions with patients about firearm safety and the discussions of other physicians that I have been aware of have been highly productive and have probably saved countless lives. The best example I can think of is talking with a primary care physician who asked me to take a look at a closet full of firearms that he convinced patients to turn into him over the years before he turned them into the police. Those patients were all depressed and suicidal and at high risk for impulsive acts. He would not have been able to make that intervention with a gag law in place preventing those discussions.

What about the President's original release?  It had 84 instances of the word "mental" usually as "mental illness" or "mental health".  As noted above it has received some accolades from the APA and other members of the mental health community. It elicited a strong and poorly thought out response from the NRA  who produced a YouTube video accusing the President of being elitist and a “hypocrite” because his daughters had armed security but he expected that everyone else’s kids would be protected by gun free zones.  The White House responded quickly:

“Most Americans agree that a president’s children should not be used as pawns in a political fight,” said Jay Carney, the White House press secretary. “But to go so far as to make the safety of the president’s children the subject of an attack ad is repugnant and cowardly.”

The full text of the White House 22 page document is located at this link.  It is ambitious and covers a lot of ground in terms of the specific regulation of firearms, school safety, and increasing mental health services. The firearm regulation is most specific in that it closes background check loopholes, bans assault weapons, outlaws armor piercing bullets, and sets the maximum magazine size at 10 cartridges.  Part of this document is a "call to Congress" so it is not clear to me how much can be accomplished by the President's executive orders as opposed to Congressional action.  I am reminded of the NRA President last weekend stating that Congress would never pass a ban on assault weapons.  The Executive Order section of that part of the document lists the following activities:

1.  Addressing unnecessary legal barriers in health laws that prevent some states from making information available about those prohibited from having guns.

2.  Improving incentives for states to share information with the system.

3.  Ensuring federal agencies share relevant information with the system.

4.  Directing the Attorney General to work with other agencies to review our

laws to make sure they are effective at identifying the dangerous or untrustworthy individuals that should not have access to guns.

The school safety initiative seems more nebulous. There is funding for 1000 "school resource officers and school based mental health professionals" and the recommendation to train 5000 additional “social workers, counselors, and psychologists.”   Considering the fact that there are probably close to 100,000 schools, this seems like a drop in the bucket.   Ensuring that each school has an emergency plan for contingencies like mass shootings does not seem to be a novel idea.  Creating safer school climates and reducing bullying has already been initiated in many school districts. There seems to be a clear lack of public health measures in the school that would reduce the likelihood of violent events.

The mental health initiative is equally lacking. In addition to the deficiencies I pointed out initially in this document, there is discussion of providing mental health training to teachers and school staff. There is probably evidence that teachers and school staff may over identify mental illness rather than under identify it.  Is this really a problem and will this level of screening be effective?   The document describes the initiative here as "increasing access" to mental health services. Screening larger numbers of students and identifying them as having potential problems actually creates a bottleneck in the system rather than increasing access.  The suggested mental health interventions in this document fall short in terms of both primary and secondary prevention of mental illness and associated aggressive behavior. Depending on a managed care model that has an established track record of dismantling the mental health infrastructure and providing limited access to poor quality care will do nothing to accommodate increasing referrals other than assure that referred students will be rapidly medicated.

My final analysis of the President’s initiative today is that it may be a starting point.  He is certainly taking the issue seriously and deserves plenty of credit for that.  His support for reopening firearm safety research that was closed by the gun lobby is important. What will become of the firearm regulation is anyone's guess at this point. The school and mental health initiatives are largely symbolic and I would not expect them to have any impact. What is sorely needed is the American Psychiatric Association coming out with standards, quality guidelines, and medical education initiatives to improve the care of people with severe mental illnesses who also happen to be aggressive.  An important piece of those guidelines should include the public health measures that were previously mentioned on this blog and those measures should also play a much larger role in any Executive initiative.

George Dawson, MD, DFAPA

Assault rifles, high capacity magazines, background checks and reverting to form

That is what it is coming down to according to the talking heads on the Sunday morning TV circuit this week.  Both the NRA and several politicians agree that there are not enough votes for an assault weapons ban.  There may be enough votes for a high capacity magazine ban but both sides acknowledge that these clips are inexpensive and there are already a lot of them out there.  The background checks issue is also debatable.  The NRA and the pro-gun factions are talking a lot about mental illness and needing to have a mechanism to prevent people with mental illnesses from getting guns.  There is minimal discussion of improved mental health services.  On CNN Sunday  morning there was acknowledgement that during tough budgetary times the line items supporting mental health treatment are the first to go.

So basically despite all of the hype about how the Sandy Hook incident was going to energize politicians to actually solve a problem – they appear to be rapidly reverting to form and not solving anything.  The NRA President seemed confident that nothing would happen (the NRA opposes any assault weapons ban or high capacity magazine ban), but cautioned that the President has a lot of political capital and might be able to influence the high capacity magazines.

I wanted to file this post tonight before the final recommendations of the Vice President because I think that there have been two recent articles in the medical literature that are very relevant. At the legislative level Jerome Kassirer, MD has a recent article in Archives of Internal Medicine. Dr. Kassirer is a former editor of the New England Journal of Medicine and I corresponded with him on this issue nearly 30 years ago.  He clearly has not lost interest over the years and brings several concepts into focus in his editorial. The first concerns the fundamentals of screening and how any effort to identify potential shooters would result in the false positives greatly outnumbering the true positives and how that renders screening impractical.  His primary focus has to do with countering political initiatives.  As an example the National Center for Injury Prevention and Control at the CDC is currently prevented from studying gun related injuries.  He advocates for countering that.  He advocates for a comprehensive analysis of gun ownership.  He also advocates for resistance to any laws that restrict physicians being able to talk about firearms with their patients. He wants to see universal background checks from gun purchases, gun safety devices including coded weapons, and restrictions on large capacity magazines and sales of large amounts of ammunition. His article refers to firearms as "Weapons of Mass Destruction".  Small arms and light weapons are in fact a major global problem.  This Federation of American Scientists primer highlights the issue and the fact that there have been over 1 million deaths due to small arms in the past decade. Some advocacy organizations estimate that as many as 250,000 people per year are killed by small arms fire worldwide.

The second very important article comes from the Journal of the American Medical Association. The authors of this article emphasize the public health approach to curbing gun violence. This is a very important concept that people have a difficult time grasping. Whenever I bring up the issue of psychiatrists being involved at the level of primary and secondary prevention most people distill that down to whether or not psychiatrists can predict violence.  A public health approach to violence prevention is much more comprehensive and multidimensional.  The authors give several good examples in this paper including modifying sociocultural norms.  They use the example of tobacco being media symbol of “modernity, autonomy, power, and sexuality" and how that was changed.  They suggest an analogous campaign to equate gun violence with weakness, irrationality, and cowardice. The article has a table that has 18 evidence-based public health interventions that have been successful in other areas that could be applied to gun violence.  This is actually the preferred strategy that I have been advocating for the past decade and the authors of this article state it very eloquently.

At this point in time it will be interesting to see if the Vice President's recommendations include any of the interventions suggested by these two articles or the recommendations from the APA.

George Dawson, MD, DFAPA

1: Kassirer JP. Weapons of Mass Destruction. Arch Intern Med. 2012 Dec 21:1-2.  doi: 10.1001/jamainternmed.2013.4026. [Epub ahead of print] PubMed PMID: 23262523.

2.  APA Recommendations to the Biden Task Force

3.  Mozaffarian D, Hemenway D, Ludwig DS. Curbing Gun Violence: Lessons From Public Health Successes. JAMA. 2013 Jan 7:1-2. doi: 10.1001/jama.2013.38. [Epub ahead of print] PubMed PMID: 23295618.

"Is once a week regular?"

"I never knew what depression was.  I knew that 'I'm kind of sad today...I'm kind of blue today,... the Reds lost.'  I knew that.  This I'm telling you you get on an elevator and the bottom drops out.  You can't stand looking at the sunlight.  You can't wait to get back in bed at night. You're shaking.  You're shivering.  I went through this for about 6 months..."  David Letterman as interviewed by Oprah Winfrey on 1/3/2013


I was out of the country for a couple of years back in the 1970s.  When I got back my younger brothers were watching David Letterman's day time TV show.  Since then I have watched him on a fairly regular basis.  Late night TV watchers often have their favorites and I there are clearly preferences based on personality differences and interview style among the various late night talk show hosts.  Letterman's reputation includes a the fact that he has a fairly quiet life style and few people seem to know the details of his private life.  This year he became a Kennedy Center honoree for his lifetime of achievement in the entertainment industry.

He was interviewed recently, first by Alec Baldwin for his public radio show Here's the Thing and earlier this evening by Oprah Winfrey for her interview series Next Chapter.  In both cases, he discusses his depression, how it affected him and even describes his understanding of why the neurotransmitters dopamine and serotonin  may be important:

" I was amazed by it. I was amazed by the chemical mechanism in your brain that can just drop you like that. And then somebody told me that, "You know what, we’re given these chemicals, these serotonins and dopamine and so forth, because if we didn’t have them, the world would scare the crap out of us." I don’t know if that’s true or not, but when I was depressed it made sense."

In the interview with Baldwin he acknowledges taking an antidepressant ("small dose of an SSRI").  In the interview with Oprah, she asks if he is seeing a psychiatrist "regularly".  He replies" "Is once a week regular?" and after that initial joke goes on to describe weekly sessions that have as the goal personal self improvement or bringing his behavior in line with the person he always thought that he was.

I liked these interviews for several reasons.  Dave's matter of fact presentation of depression, how severe it was and the way it impacted his life was striking.  In a few sentences he was able to contrast it with sadness related to disappointments in life and explain how it allowed him to empathize with people.  Prior to experiencing depression himself he was likely to consider depression something that you should just get over on your own: "Go do some push-ups and you’ll feel better." .  He describes both medical treatment of depression and psychotherapeutic treatment.  His primary care physician was instrumental in referring him for treatment.  He also discussed the overall goal of his current psychological therapy.

I am sure that in the days that follow, the networks will have their medical consultants out there with some talking points on depression.  A discussion of depression as a risk factor for coronary artery disease might be one example.  For the sake of this post, he communicated the problems at several levels very well in just a few sentences and I hope that people get to see and listen to these interviews.

George Dawson, MD, DFAPA

Alec Baldwin.  Here's the Thing Transcript of David Letterman Interview June 18,2012.  (depression segment starts 2/3 of the page down).

Oprah Winfrey.  Next Chapter Transcript of David Letterman Interview January 6, 2013. (depression segment starts 2/3 of the second page down).

A Psychiatrist Reads the Washington Post

There are an endless number of ways that the appearance of conflict of interest can be spun to make any organization look bad.  The obvious question is why that always seems to occur with psychiatry?  The arguments all follow the general form that a financial benefit resulting from work related to the pharmaceutical industry disqualifies those experts from writing objective research about medication or rendering opinions about the treatment of psychiatric disorders in general. That is the theme of the latest article from The Washington Post entitled “Antidepressants treat grief? Psychiatry panelists with ties to drug industry say yes."  It is an old story with little variation and I add some commentary based on the organization of the article.

"In what some prominent critics have called a bonanza for drug companies, the American Psychiatric Association this month voted to drop the old wording against diagnosing depression in the bereaved, opening the way for more of them to be diagnosed with major depression and thus, treated with antidepressants.”

This statement assumes that this practice is not occurring right now. In fact, it is widely known that the diagnosis of depression is not rigorously made in primary care settings. It is highly likely right now that patients suffering from grief as well as psychological adaptations to acute stress are being treated with antidepressants. There is no reason to believe that the patients being treated in primary care resemble the patients with a diagnosis of major depression in clinical trials of antidepressants.

"The change in the handbook, which could have significant financial implications for the $10 billion  US antidepressant market, was developed in large part by people affiliated with the pharmaceutical industry, an examination of financial disclosures shows.”

The previous statement talks about a "bonanza for drug companies" and builds on this image in the second statement. It ignores the fact that most commonly prescribed antidepressants are currently generics and available for as little as four dollars per month. The only two major antidepressants at this time that are not generics are Cymbalta (duloxetine) and Vibryd (vilazodone).  Where does the "10 billion dollar" figure come from?  If you read the entire article on page 5, that figure was from IMS America a company that tracks total prescriptions from American retail pharmacies.  Anyone knowing the applications for antidepressants would know that they are prescribed for many conditions other than depression including headaches, hot flashes, and chronic pain. The total retail sales figure is unlikely to reflect either drug company profits or the amount of depression being treated.

A little arithmetic is always instructive. If we assume that a physician prescribes a generic antidepressant for a patient that costs four dollars per month that translates to a total cost of $48 per year. The $10 billion/year figure quoted here would represent 208 million prescriptions or 66% of the entire population of  the U.S. taking antidepressants 12 months out of the year.  Even if we take $2 billion out of the $10 billion figure for Cymbalta and Vibryd, that results in 53% of the population taking antidepressants 12 months out of the year. Those figures are 5-8 times higher than any actual estimation of antidepressant use.  The $10 billion dollar figure is certainly eye-opening but there is plenty of evidence that it is not remotely accurate and will not have the purported impact on the pharmaceutical industry.

"About 80% of the prescriptions for antidepressants are written by primary-care physicians and others, not psychiatrists, a fact that makes the APA handbook particularly important. Faced with a patient complaining of depression-like symptoms, a general practitioner may be likely to rely on the Association's handbook for advice.”

This statement reveals the authors lack of knowledge about the practice of medicine and about the DSM that he is criticizing. The DSM is strictly a diagnostic manual and it contains no treatment recommendations. Primary care physicians are not avid readers of the DSM and that has probably led to the practice of using a DSM-based checklist – the PHQ-9.  This practice has not been promoted by the APA or the pharmaceutical industry (although the PHQ-9 is copyrighted by Pfizer pharmaceuticals).  Using a checklist to make a rapid diagnoses (in minutes) and rapidly treat large numbers of patients is promoted by managed care organizations and HMOs. That is probably the single greatest factor contributing to antidepressant prescriptions but it is ignored by the author - probably because it challenges his contention that this is all driven by conflict of interest in psychiatry rather than the business world.  It is cheaper for HMOs to treat depression with medications rather than detailed psychiatric assessments and psychotherapy.

"The Association itself runs on a budget of about 50 million a year, and for years industry funding has been critical to its operations. Today, about 14% of the Association's budget comes from pharmaceutical companies, mainly in the form of advertising at annual meetings and publications."

The author does a good job of providing no context here. Is the APA any different from other medical specialty organizations? Does advertising create a conflict of interest? Is any other print media outlet held to that standard? There is information available in those areas.   An Institute of Medicine report focused on conflict of interest showed that the APA's revenue from the pharmaceutical industry was in the middle of the pack with regard to medical specialty societies. As an example, the year that report was done the APA reported that medical companies supplied 28% of their annual income.  The American Academy of Family Physicians reported that 42% of their annual income was from pharmaceutical companies (p 220).  That same report (Recommendation 6.1) noted that increasing work for the pharmaceutical industry correlated with a 7% reduction in real physician wages and recommended that there was nothing wrong with “consulting arrangements based on written contracts for expert services to be paid for at fair market value”.   Depending on the expert involved, restricting the amount to $10,000 per year could practically mean anywhere from 2 to 10 presentations per year or about 2 1/2 weeks of contract work. 

“Other members of the committee have numerous ties to drug companies, too, and not simply conducting research, according to disclosures from last year. One was holding stock in Glaxo Smith Kline, one was a consultant to Servier and another consultant to Pfizer;  one had a grant from AstraZeneca and another a grant from Pfizer and AstraZeneca.”

This is a paragraph from a poorly written section illustrating ties between the 11 member Mood Disorders Work Group set up to draft the guidelines on major depression. There is some explanation of the selection criteria and conflict of interest criteria.  It discusses conflictof interest criteria that the APA designed and made explicit in response to this article.  It provides no context other than an off hand remark by the chairman that he probably regrets making. The article provides no reasonable context for expected reimbursement for experts as consultants to industries or the fact that this is a common practice in many academic departments on any major university campus. In some of those industries, the professional organizations actually make an effort to make sure that businesses are well represented in any process that involves making standards.

"The current handbook-the revised version will be published in the Spring-recommended against diagnosing major depression in the bereaved when the symptoms are milder and of less than two months duration. This is known as the "bereavement exclusion".  (If the signs of depression are severe-the patient has thoughts of suicide, for example-major depression is supposed to be diagnosed)….. The new handbook removes the bereavement exclusion."

There is really nothing new and nothing drastic as anticipated with removing the "bereavement exclusion". To provide a clear example I will quote a text copyrighted in 1982:

"There are many publications that deal with treating psychiatric patients who report recent and remote bereavement. It is possible to find a real or imagined loss in every patient's past. However, for the most part, because there is little evidence from reviewing normal bereavement that there is a strong correlation between bereavement and first entry into psychiatric care, those bereaved who are seen by psychiatrists should be treated for their primary symptoms. This is not to say that the death should not be discussed, but because these people represent a very small subset of all recently bereaved, they should be treated like other patients with similar symptoms but no precipitating cause. A physician seeing a recently bereaved with newly discovered hypertension might delay treatment one or two visits to confirm its continued existence, but treat it if it persists. So the psychiatrist should treat the patient with affective symptoms with somatic therapy but only if the symptoms are major and persist unduly. A careful history of past and present drug and alcohol intake is indicated. Then, the safest and most appropriate drugs to use are the antidepressants. Electroconvulsive therapy is indicated in the suicidal depressed." (Paykel p413-414).

Any psychiatrist worth his or her salt knows the difference between grief and depression and they should know the literature on treating grief, the natural history of grief, and the research on proven non-medical treatment of grief including Interpersonal Psychotherapy (IPT) and grief counseling. When you are seeing a psychiatrist, you are seeing an expert who should know the literature on grief, depression, and the differential diagnosis of depression.  Nothing in this article indicates that.  In fact, quotes are provided to suggest that the APA and psychiatry in general has an interest in redefining “the range of acceptable emotion” rather than using clinical research done by psychiatrists to limit suffering and prevent suicide.

I think the reality here indicates that there is no scandal.  The importance of the DSM-5, the appearance of conflict of interest, and the potential windfall for the pharmaceutical industry appear to be seriously overestimated.  Organized psychiatry is certainly not responsible for what happens  in primary care clinics under the direct guidance of business organizations.  There is a responsibility to establish professional standards for patients referred to psychiatrists for the assessment and treatment of complicated depressions that may occur during bereavement. The suggestion that medications may be useful in some of these situations and the importance of treating depression in bereavement has been around for at least 30 years.

George Dawson, MD, DFAPA

Peter Whoriskey.  Antidepressants to treat grief? Psychiatry panelists with ties to drug industry say yes. The Washington Post, December 26, 2012.

Clayton PJ. Bereavement in Handbook of Affective of Disorders.  Eugene S. Paykel (ed). The Guilford Press. New York. 1982  pages 413-414.

APA Reiterates Stringent Rules on Accepting Pharma Support.  Psychiatric News.  Monday December 31,2012.

Institute of Medicine (US) Committee on Conflict of Interest in Medical Research, Education, and Practice; Lo B, Field MJ, editors. Conflict of Interest in Medical Research, Education, and Practice. Washington (DC): National Academies Press (US); 2009. Available from: http://www.ncbi.nlm.nih.gov/books/NBK22942/  

 

Dr. Dawson's Neighborhood

 “Politicized science is an inevitable part of the human condition, but society must strive to control it. Although history shows that politicized science does much more damage in totalitarian societies than in democracies, even democracies are sometimes stampeded into doing very foolish and damaging things." – William Happer, Harmful Politicization of Science in Politicizing Science: The Alchemy of Policymaking

When I was a kid, I walked five blocks a day back and forth to primary school and kindergarten for the first seven years of my schooling. I got to know the people along that route very well. In those days in a small town people looked out for you when you were a kid. They offered you things to eat and you knew it was safe to eat.  You got to know their problems.  They told me about being gassed in World War I and never getting over it or drinking a pint of gin a day for thirty years and then stopping.  Some were engaged in behaviors that were difficult to explain such as laughing uncontrollably or making statements that seemed to be directed to you but that did not make any sense. Other people told me about their neighbors having alcoholism or having undergone shock treatments. There were adults with developmental disabilities. I visited several families with my parents and I can remember witnessing shocking behavior in those private residences - shocking for a kid but not so much for a psychiatrist.  Plenty of shocking events happened right at my own home.  That was my neighborhood as a kid and I lived there a long time.

Over the next four decades, I have thought a lot about my old neighborhood from time to time. The most frequent thought I get is how common psychiatric disorders are and how they are easily recognized by most people in your neighborhood.  The second most frequent thought I get is how there was nearly a complete lack of professional help for people with those problems. There was an extremely high threshold for assistance and when that threshold was met people were often sent hundreds of miles away to institutions until they recovered or remained in those institutions on an indefinite basis.  Some of these institutions doubled as sanatoriums for the mentally ill and patients with tuberculosis.  My aunt was a nurse in one of those places and was assaulted.  I can remember thinking: “Why would somebody with TB attack her?”

My mother had severe bipolar disorder, and was treated for years with tricyclic antidepressants by her family physicians. She eventually was able to see a psychiatrist and got more appropriate mood stabilization, but only after decades of mood instability.  My father seemed very depressed and lethargic. He probably had obstructive sleep apnea, a condition that psychiatrists routinely screen for these days but back then it was unknown. I found him dead one morning when he was 42 years old.  Medical treatment in general was pretty bad in those days.  Treatment for mental illness and access to psychiatry was practically nonexistent.  

There was no DSM when I was walking back and forth from school.  And yet the people with mental illnesses who were impaired were obvious to most people. That consensus was necessary, because their neighbors knew that they had to be more patient and kind based on those problems.  They knew they had to keep children from teasing or ridiculing these folks and teach them how to treat the disabled.  Some of our neighbors who interacted with my mother were incredibly tolerant at all hours of the day or night.   I don't know where I would have ended up without that level of assistance and recognition that there was a huge problem.  I think that level of common sense prevails today and is the basis of studies that look at whether or not psychiatric disorders are considered to be "diseases" by most people.  Those survey studies generally show that most people view severe mental illnesses and addictions as diseases. The idea that there is no such thing as a psychiatric disorder, forms the basis of anti-psychiatry rhetoric, but it is not rooted in reality or common sense.  The average person on the street does not need a DSM to detect mental illness.

The reality of psychiatric disorders and their treatment is really the focus of this blog.  It is something I have been focused on since before I became a psychiatrist.  Psychiatry is the most politicized and maligned medical specialty. It is rarely covered in an objective manner by the media. It has been manipulated by businesses and the government for their mutual advantage. It is the only specialty where there are significant profits made from continuously criticizing every aspect of the discipline.  It has few rational and fewer effective advocates.     

I continue this blog with those thoughts and the memories of my old neighborhood in mind and wish any readers here a Happy New Year.