Will Changing The Commitment Standard Decrease The Rates Of Mass Shootings?

A colleague sent me an e-mail this morning about a story that focuses on changing the commitment standard to a need for treatment rather than dangerousness.  She asked me if I thought it would be an effective measure so that more people with psychosis are treated decreasing the risk of mass violence perpetrated by psychotic persons.  As a background, most states have civil commitment statutes that involve imminent dangerousness.  That literally means that the person in question has already done something dangerous or they appear to be at high risk for doing something dangerous in the near future.  My first reaction is that it would not do a thing and here is why - states routinely ignore lesser standards and default to dangerousness because it limits court and treatment costs.  At least until there is a "bad outcome" and then for a while the standard is broadened again.

Let me illustrate what I mean by using the statutes that pertain to civil commitment in the state of Minnesota.  The following are the statutory definitions of a mentally ill or chemically dependent person who could be considered for civil commitment in the state:

Subd. 13.Person who is mentally ill.

(a) A "person who is mentally ill" means any person who has an organic disorder of the brain or a substantial psychiatric disorder of thought, mood, perception, orientation, or memory which grossly impairs judgment, behavior, capacity to recognize reality, or to reason or understand, which is manifested by instances of grossly disturbed behavior or faulty perceptions and poses a substantial likelihood of physical harm to self or others as demonstrated by:

(1) a failure to obtain necessary food, clothing, shelter, or medical care as a result of the impairment;

(2) an inability for reasons other than indigence to obtain necessary food, clothing, shelter, or medical care as a result of the impairment and it is more probable than not that the person will suffer substantial harm, significant psychiatric deterioration or debilitation, or serious illness, unless appropriate treatment and services are provided;

(3) a recent attempt or threat to physically harm self or others; or

(4) recent and volitional conduct involving significant damage to substantial property.

(b) A person is not mentally ill under this section if the impairment is solely due to:

(1) epilepsy;

(2) developmental disability;

(3) brief periods of intoxication caused by alcohol, drugs, or other mind-altering substances; or

(4) dependence upon or addiction to any alcohol, drugs, or other mind-altering substances.

Subd. 2.Chemically dependent person.

"Chemically dependent person" means any person (a) determined as being incapable of self-management or management of personal affairs by reason of the habitual and excessive use of alcohol, drugs, or other mind-altering substances; and (b) whose recent conduct as a result of habitual and excessive use of alcohol, drugs, or other mind-altering substances poses a substantial likelihood of physical harm to self or others as demonstrated by (i) a recent attempt or threat to physically harm self or others, (ii) evidence of recent serious physical problems, or (iii) a failure to obtain necessary food, clothing, shelter, or medical care. "Chemically dependent person" also means a pregnant woman who has engaged during the pregnancy in habitual or excessive use, for a nonmedical purpose, of any of the following substances or their derivatives: opium, cocaine, heroin, phencyclidine, methamphetamine, amphetamine, tetrahydrocannabinol, or alcohol.

The first thing that should jump out at any reader is the fact that "dangerousness" most commonly defined as a "danger to self or others" is only one of several relevant criteria (see bolded sections).  A significant part of the statutory definitions for both mentally ill persons and chemically dependent persons has to do with self care.  Can they provide food, clothing, shelter, or medical care for themselves?  Can they manage their personal affairs?  I would suggest that the majority of people in this country with psychotic disorders and both substance use and psychotic disorders who are acutely disabled by those disorders meet this standard rather than threatening or aggressive behavior.  Suicidal ideation and behavior is also less common than deficits in functional capacity or self care.  There are also a number of important legal interventions that are as important as civil commitment to address these issues among them conservatorship or guardianship that provides substituted decision making for the person with impaired cognition due to mental illness.  I worked with an even better option in the State of Wisconsin and that was a parallel system of protective services and protective placement that could be used in place of civil commitment to assure that the person had adequate resources for their day to day needs and medical care.

The article I received today talks about mental health being the default position for legislators who do not want to take on the firearms issue.  The politics of this situation and the deadlock  are quite obvious so I won't belabor the point.  The legislator in this reference wants better training for the police and a commitment standard based on treatment considerations rather than "imminent dangerousness."  I have already demonstrated how imminent dangerousness is a de facto standard that the courts and managed care systems collude with, but it really has nothing to do with existing statutes on the books.  I will take a page from the gun advocates who claim we have enough gun legislation on the books it is just never enforced.  We have enough commitment standards on the books - they are never recognized or followed.  To say that the commitment standard is "imminent dangerousness" is simply false.    

The politics of civil commitment is always an interesting process and it does shed some light on why the standards are ignored.  It actually happens at all levels.  In Minnesota, if a person is on a 72 hold in a hospital they need to be seen during that time frame by a pre-petition screener from their county of residence. Pre-petition screeners come from many counties and they vary considerably in their clinical acumen and political orientation.  It becomes fairly easy to predict which counties will proceed with commitment and which will not.  Some counties have pre-petition screeners who actually consider themselves to be civil rights advocates and they will fight any suggestion of commitment.  That fight should occur at the next level and that is the county attorneys who represent the county in the commitments and the defense attorneys.  Outcomes vary with the personality of those attorneys and some of those outcomes are not good.  The final step is the probate court judge, commissioner, or referee responsible for making the determination of commitment.  The quality and experience at this level varies considerably ranging from judges who are consistent and handle cases very well to those who clearly make wrong decisions to judges who overstep their authority and start to make medical decisions such as ordering a specific medication or quantity of mediation per court order.  As far as I can tell there is no uniform training or standards for any member of the commitment process so variable outcomes should not come as a surprise.    

With the issue of civil commitment laws that use a treatment standard, they are already on the books but  they are rarely followed.  That has to do with the culture of rationing mental health services as much as anything.  How do I know this?  I have been part of conversations where staff involved in a commitment were told by a county bureaucrat that they were doing "too many commitments" and it was "costing the county too much money".  I never really understood that argument because all of the people involved are there, on salary, and show up every day whether there is anyone in commitment court or not.  The cost should be the same if one person shows up for a hearing or 20 people show up.  At 5 o'clock everybody goes home, so there is no overtime.  I have never seen the court so saturated that they could not move through the necessary hearings and decisions.  The only thing that this false economic pressure creates is a change in the way the commitment statute is interpreted.  Suddenly the ONLY rule is "dangerousness to self or others".  That also translates to "imminently dangerous to self or others".  Notice that the statute says nothing about "imminently" and any form of the word danger is limited to a special section at the bottom about "Mentally Ill and Dangerous".    

I conclude the changing the commitment standard and expecting that to have an impact on mass violence will not work, basically because that treatment standard is already on the books and it is routinely ignored.  In Minnesota, the entire chemically dependent person statute is frequently ignored and I often hear "we don't commit anybody for chemical dependency."  There are a number of financial, avoidance of work incentives, and lack of quality standards that have facilitated that process.  It is readily observable by any psychiatrist who sees their patient back, realizes that they did not receive any care in a hospital, and notes the patient was discharged at his or her request because "they were not imminently dangerous".  The financial interests of managed care systems and the counties involved overlap perfectly at that point.

Once again I keep coming back to the old term "quality".  Quality care never involves discharging a disabled person because it is convenient to do so and it can be rationalized by a "community standard" that is determined by everybody except the experts involved and in this case the state statutes..

The focus of psychiatric professional organizations should be on defining what that standard of care should be and how to optimize treatment instead of throwing in with a managed care model for rationing care.  Rationed care has resulted in a non-existent system of care for the patients with psychosis.  And as long as that system remains non-functional, the small percentage of people who are violent and psychotic will also not get the care they need.

The prevention of violence by individuals with psychosis starts with improving the standard of care for everybody rather then trying to pick the violent individuals out of the crowd. 

George Dawson, MD, DFAPA 

Rampage Killing - The Public Health Approach Is Still Ignored

I was watching the news this morning on the latest rampage killing.  This news coverage features numerous replays of a YouTube video posted by the killer about twenty minutes before he started shooting.  I listened to an expert, (at least as much of an expert as you can be) talk about his approach to the problem.  He talked about the limitations of the post event "psychoanalysis" of the  killer and how a more functional approach would be to harden targets and warn the victims.  He talked about the false positive rate of how most people who threaten or post videos like this do not carry out the threatened violence making it impossible to detain all the people making the threats.  He said that it may be useful to talk to people with these problems but the psychology of this individual not only made that impossible, but even talking with mental health professionals was not likely to help him.

I had just finished reading the latest Psychiatric Annals.  This month's topic was Psychotic Rampage Killers.  Three of the four articles were written by C. Ray Lake, MD,  and the fourth by James l. Knoll, MD and J. Reid Meloy, PhD.  Dr. Lake also had an opinion piece on why mass murder diagnoses were justification for breaking the Goldwater Rule specifically the part ".... it is unethical for a psychiatrist to offer a professional opinion unless he or she has conducted an examination and has been granted proper authorization for such a statement."  He points out that this rule is currently routinely broken with speculative diagnoses about psychotic mass killers.  He also suggests that the correct diagnosis is still an open question.  He also points out that the inadequate care of individuals with psychosis is an issue and that has been one of the themes of this blog.

Lake's main contention is that Psychotic Rampage Killers are really bipolar and manic and do not have schizophrenia.  He briefly reviews some of the facts including that even though a small percentage of killers (<10%) are psychotic, there are a distinct number of correlates that cause them to differ from non-psychotic killers most notably a motivation that is delusional in nature, the fact that they are always caught (as opposed to 33% of non-psychotic killers never being caught), warnings  and plans prior to the act are common, and half attempt or commit suicide.  The psychotic killer basically focuses on the event as a final stage and does not plan to escape or benefit from the event.  He makes the point that all of the psychotic killers realize that what they are doing is illegal and that can exclude an insanity defense if they survive.  I think this is also a common misconception on the part of the public.  People who are psychotic can carry out detailed plans that are consistent with the logic of their psychosis.  It certainly does not mean that they are rational.  He briefly reviews the issue of violence and psychosis and takes on the political issue that "violence perpetrated by mentally ill is no greater than violence carried out by the non-mentally ill population."  This has always been a statistical fallacy balancing the violence by a subgroup of the mentally ill against the violence of high risk members in the general population.  By now there should be no doubt that some people with severe mental illness have a much higher rate of violence than the general population.   Further there are known diagnostic features within that subgroup that are associated with the increased risk of violence including alcohol and drug addiction, paranoia, command hallucinations, and a lack of treatment.

Lake's initial discussion of prevention points out that gun legislation is not likely to be a solution because of existing biases by legislators in this area to do nothing despite the fact that most rampage killer use firearms and 75% of them were legally acquired.  Civil commitment laws were described as "limited by our sensitivity to personal freedoms."  In my experience, it comes down to the courts involved and the administrative element through the involved counties.  I have been personally involved in thousands of civil commitments and decisions by the courts often depend on the most recent "mistake" defined as an adverse outcome that occurred when a potentially violent person was released.  Certainly any case involving firearms and hundreds of rounds of ammunition or an actual shoot out with the police needs very close scrutiny.  Any "welfare check" by the police of a potentially dangerous person should involve a search for weapons and actual threats especially if they were posted on social media.  Mental health professional contact was described as being potentially useful but also limited by the nature of the follow up of patients with psychosis.  In fact, violence needs to be incorporated into the treatment  plan for patients with psychosis and violence and addressed in a comprehensive manner.  An appointment for a ten minute discussion of medications is not acceptable and it really is not an acceptable level of care for anyone with psychosis whether they are potentially violent or not.  Lake points out that there is also a call to avoid using the names and other materials posted by rampage killers.  I think that is a good idea and therefore do not refer to any of these materials here.

The discussion of what is the proper diagnosis of these murderers is the next article. Lake reviews the evidence (largely from media reports) and concludes that psychotic mania is the most likely diagnosis.  He has an interesting diagram in the article that shows both psychotic depression and psychotic mania converging on the diagnosis of "paranoid psychosis from mood disorders".  He also has interesting graphic using Venn diagram approaches that range from Kraepelin's initial clear distinction between bipolar disorder and schizophrenia to the more spectrum based approach beginning with Timothy Crow's continuum with schizophrenia and bipolar disorder being at opposite ends of the spectrum.  He expressed some surprise that schizoaffective disorder was still in the DSM-5, but it also considers Schizophrenia Spectrum and Other Psychotic Disorders separate from Bipolar and Related Disorders.  In reviewing the details from the media of five Rampage Killers, he concludes that in all cases psychotic mania was a diagnostic consideration based on hyperactivity, insomnia, and delusional thinking.  In one case there was a family history of bipolar disorder.

Lake goes on to point out that without an accurate diagnosis of bipolar disorder, patients do not receive standard of care which he defines as mood-stabilizing drugs.  He digresses to talk about the legal profession changing the diagnostic habits of professional and uses false memory syndrome as a case in point.  He goes on to suggest that "Successful legal action in the form of a class action lawsuit filed on behalf of unrecognized bipolar disorder misdiagnosed with and mistreated for schizophrenia could quickly change psychiatric diagnostic practices.  Another potential class action lawsuit is possible from some of the mass murder victims families in cases where before the rampage, the psychotic murderer had been treated for schizophrenia and not bipolar disorder."  Dr. Lake considers the problem basically to be one of "obsolete diagnostic concepts that promote substandard medical care for psychotic patients."

In 30 years of practice, I have not made the same observations that Dr. Lake has made.  In the example of false memory syndrome, that diagnosis and the associated multiple personality disorder phenomena was really practiced by a small minority of psychiatrists.  It was actively criticized at the time by prominent psychiatrists in prominent journals.  I  doubt that lawsuits against anyone had any impact on the diagnostic concepts of the vast majority of psychiatrists.  On the issue of diagnosing bipolar disorder based on a spectrum concept and the features of hyperactivity and insomnia. I would suggest that is fraught with problems.  Having seen patients over time patients with schizophrenia can also have these features. The same problems occur when considering standard of care arguments for mood stabilizers.  All of them (lithium, divalproex, lamotrigine) have significant problems with both efficacy and side effects profiles.  Antipsychotic medication is probably necessary in at least 50% of bipolar patients (in addition to the mood stabilizer), and many antipsychotics are FDA approved for acute bipolar disorder and bipolar depression.  But the larger problem is that there needs to be a standard of care than encompasses much more than medication.  That is good for all patients with psychosis and potentially very good for those at risk for violence.

The recommendations I have discussed before on this blog that I think will have the most impact would be:

1.  Establish centers of excellence for treating psychotic disorders.  We know the outcome of rationing mental health services.  We end up with inadequate inpatient and outpatient care for patients with psychosis and bipolar disorder.  The focus of all for profit systems is to transfer the cost of care for these individuals to public systems including correctional facilities.  If they end up being cared for in a for profit system, the care is concentrated on their ability to see a physician or more appropriately a "prescriber" for about 10-20 minutes and accurately describe their problems.  It is well known that psychotic rampage killers do not consider their homicidal ideation to be a problem and may actively try to hide those thoughts from any interviewer.

2.  A standardized approach to law enforcement intervention.  Law enforcement has a number of possible interventions available to them that are not available to mental health professionals.  The duty to warn legislation has blurred these distinctions and essentially removed a lot of responsibility from law enforcement.  There is really no reason why a person posting obvious threats on the Internet should not be treated with the same degree of caution as perpetrators of domestic violence.  That would include proscriptions against owning and acquiring firearms, police surveillance and where necessary orders for protection.  Threats to kill should trigger a response that involves a search for firearms and materials showing a plan to perpetrate violence.

3.  A public health approach focused on the issue of homicidal ideation as a potential symptom of mental illness.  The public and the patients themselves need to be able to conceptualize this problem as an illness and a symptom that does not need to be acted upon.  The article reference here refer to outdated diagnostic concepts and I would include the idea that patients with psychosis especially delusions cannot modify their thinking by means other than medication.  It certainly happens in response to events but also as a result of psychotherapy.

4.  Comprehensive outpatient care.  Brief checks focused on medications are doomed to fail.  These patients and all patients with psychoses need comprehensive outpatient care that includes home visits when necessary, psychotherapy, comprehensive cognitive assessments, and vocational rehabilitation.  When I first started working these were all available in my clinic.  Today it is unheard of.

Psychosis and psychotic people who kill are the psychiatric equivalent of a heart attack.  Any middle aged person in the country with chest pain gets admitted and goes through about 24 hours of comprehensive testing and imaging.  I don't know the actual statistics but I would guess that most of these people are not having heart attacks and their hospital and Cardiology bill is about $30,000 - $50,000.  Our system of care expects a person with psychosis who is totally unaware of the fact that they have a significant disturbance in their thinking to want to actively manage that illness on resources that are trivial in comparison.  In the case of an identified heart attack, that person will receive hundreds of thousands of dollars of additional care.  By comparison a person receiving the most comprehensive level of community care - Assertive Community Treatment or ACT receives those services for about $10,000 per year.  That service is typically limited to a few hundred people in each state and not covered by medical insurance.

The best approach to rampage killers is to offer a much better standard of care to all people with psychosis.  If it the right thing to do from the perspective of psychiatry, public health, and humanism.

George Dawson, MD, DFAPA

Lake CR.  Rampage murders, Part I: Psychotic versus non-psychotic and a role for psychiatry in prevention.  Psychiatric Annals 2104 (44) 5: 216-225.

Lake CR.  Psychotic rampage murders, Part II: Psychotic mania, not schizophrenia.  Psychiatric Annals 2104 (44) 5: 216-225.

Supplementary 1:

"Charges for chest pain, for instance, rose 10 percent to an average of $18,505 in 2012, from $16,815 in 2011. Average hospital charges for digestive disorders climbed 8.5 percent to nearly $22,000, from $20,278 in 2011."

J Creswell, S Fink, S Cohen.  Hospital Charges Surge for Common Ailments, Data Shows.  New York Times; June 2, 2014.

Vortioxetine

I have been hearing about the new antidepressant vortioxetine (marketed under the brand name Brintellix).  I decided to post something about it because there have been numerous searches that resulted in hits on this blog looking for information on this medication.  As a consultant, I am probably not in the best position to start prescribing this medication.  The majority of the people I see are already on at least one antidepressant and they have typically tried many.  The  common mistakes of ten years ago like inadequate dosing are not as prevalent.  Augmentation strategies like the addition of bupropion, aripiprazole, and buspirone are common. In primary care settings nobody uses lithium or T3 anymore.  Apart from mood disorder specialists, nobody uses monoamine oxidase inhibitors.  I am just getting to the point where I am seeing people who have responded to vilazodone when nothing else seemed to work.  Even then the numbers are very low.  

What if anything is unique about vortioxetine?

Looking at the package insert, it is approved for the treatment of major depressive disorder and nothing else.  The date of approval was 9/30/2013.  It has the standard contraindications, black box warning and warnings of most antidepressants.  It is a substrate of CYP2D6 and therefore the dose needs to be decreased with inhibitors and increased with inducers of this enzyme.  Other cytochromes CYP3A4/5, CYP2C19, CYP2C9, CYP2A6, CYP2C8, and CYP2B6 also play minor roles in the metabolism.  The metabolite is inactive.   Discontinuation symptoms are also mentioned in the package insert citing headaches and muscle tension following abrupt discontinuation.  The manufacturer states that in anyone taking 15 or 20 mg/day that the dose should be decreased to 10 mg/day for a week before discontinuation is done.  Vortioxetine has a 66 hour half-life.

There is generally more detailed pharmaceutical and pharmacodynamic information in recent FDA approved package inserts and vortioxetine is no exception.  As noted in the graphic below it is a potent inhibitor of serotonin reuptake by 5-HTT (SERT) on the same order of magnitude as escitalopram.  The pharmacology of serotonin receptors (right column) is complex.  I have highlighted the serotonin receptors that vortioxetine binds to with Kis of < 100 nM.  The drug is also an antagonist at 5-HT3, 5-HT1D, 5-HT7, a 5-HT1B partial agonist, and a 5-HT1A receptor agonist. (all values in package insert).

Serotonin pharmacology is complex.  One review (2) written by PharmDs with no financial conflicts of interest described the vortioxetine as a "novel multimodal antidepressant agent with a complex mechanism of action".  They suggest that the pharmacodynamic profile "results in increased levels of serotonin, norepinephrine, dopamine, acetylcholine, and histamine."  Interestingly, there has been no comment that it has a greater binding affinity (113) for the norepinephrine transporter (NET) than SNRI venlaxine (385) but not the SNRI duloxetine (70). (see table below).

Also contained in this package insert is information about serotonin receptor occupancy based on imaging studies.  Two clinical Positron Emission Tomography (PET) studies using 5-HTT ligands showed 50%, 65%, and 80% occupancy at doses of 5, 10, and 20 mg/day respectively.

 

Clinical trials results were also described in the package insert.  There w ere 6-8 week double blind placebo controlled studies using the HAM-D and MADRS as outcome measures.  Six studies are plotted on a mean change from baseline plot and all were better than placebo at week 6 or 8 but in 2/11 measurement the error bar touched or went past the no difference from placebo line.   The results of a maintenance study were also described that looked at the results of  randomizing 396 patients in remission to continuation treatment of vortioxetine 10 mg/day or placebo.  The survival analysis showed significantly longer remission of depression in the vortioxetine group.  Using an effect estimation approach the Number Needed To Treat/Harm (NNT/NNH) was 7 (NNT) for response, 11 (NNT) for remission, and 36 (NNH).  In the review article the authors describe a total of 10 short term clinical trials and 6 with an active comparator.  In 5/6 the active comparator ws duloxetine 60 mg/day and in the other it was venlafaxine extended release 225 mg/day.  All 6 of the comparator trials were run against placebo.

Like other serotonergic agents nausea and diarrhea were the most common reasons for discontinuation and the likelihood was dose dependent at significant rates (21-36% vs 9% on placebo).  Sexual dysfunction was measured in 7 of the clinical trials using the Arizona Sexual experiences Scale (ASEX) after baseline rates were established by other clinical means.  The initial rates were 3-5% for men and 1-2% in women.  Using the ASEX, the rates ranged from 22-34% in women versus 20% placebo and 16-29% in men versus 14% placebo.  The most interesting side effect for me was headaches.  There are seven references to head in the package insert and all of them are in discussions of discontinuation symptoms or as a sign of hyponatremia.  I could not find it listed as a side effect.  In looking at the review (2) this may be an artifact of the high rate of headache (7.6-24.8%) in the placebo group.  Overall rates of discontinuation from the clinical trials compared to placebo were low.

At this point vortioxetine is described as a moderately effective antidepressant with a purported novel mechanism of action.  There has been relatively limited exposure of 2616 people in clinical trials.  I expect the pricing to reflect the usual high price of a novel antidepressant medication and in most managed care and pharmacy systems it will require prior authorization and documentation that other medication trials have failed.  From the clinicians perspective, I will be cautious when using it with other medications that have potential pharmacodynamic and pharmacokinetic effects.  The disclaimer that vortioxetine had an effect of cardiac repolarization that was "below 10 ms the threshold for regulatory concern" will not deter me from doing the necessary evaluation in patients who are taking combinations of medications that affect cardiac conduction or present with new cardiac symptoms.  I will also try to provide some discussion of the unknowns to people who are looking for the next medication that might be effective for chronic depression.  In doing that I am going to renew my membership in the ACS for access to a more detailed discussion of the medicinal chemistry involved (reference 3).

George Dawson, MD, DFAPA

1.  Brintellix (vortioxetine) FDA approved package insert.

2. Pearce EF, Murphy JA. Vortioxetine for the treatment of depression. AnnPharmacother. 2014 Jun;48(6):758-65. doi: 10.1177/1060028014528305. Epub 2014 Mar 27. PubMed PMID: 24676550.

3. Bang-Andersen B, Ruhland T, Jørgensen M, Smith G, Frederiksen K, Jensen KG,Zhong H, Nielsen SM, Hogg S, Mørk A, Stensbøl TB. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. PubMed PMID: 21486038.

Minnesota Passes Medical Marijuana "Research" Bill

It's official.  Both houses of the Minnesota legislature passed a medical marijuana bill last Friday night.  The Governor has already said that he would sign it.  Minnesota ended up taking a unique approach largely because the Governor said he would sign no bill that was not accepted by law enforcement.  The process was also affected by the medical society who did not want physicians in the prescribing loop and the psychiatric society who did not want psychiatric disorders used as an indication for marijuana.

That effectively took marijuana smoking off the table.  The turning point was apparently young mothers testifying that cannabis derivatives were critical to the treatment of refractory epilepsy.  At that point there were several new drafts of the bill looking at the indications, the physicians role, and the role of the government.  The agreed upon indications follow:


Subd. 14. Qualifying medical condition. "Qualifying medical condition" means a
3.15diagnosis of any of the following conditions:
3.16(1) cancer, if the underlying condition or treatment produces one or more of the
3.17following:
3.18(i) severe or chronic pain;
3.19(ii) nausea or severe vomiting; or
3.20(iii) cachexia or severe wasting;
3.21(2) glaucoma;
3.22(3) human immunodeficiency virus or acquired immune deficiency syndrome;
3.23(4) Tourette's syndrome;
3.24(5) amyotrophic lateral sclerosis;
3.25(6) seizures, including those characteristic of epilepsy;
3.26(7) severe and persistent muscle spasms, including those characteristic of multiple
3.27sclerosis;
3.28(8) Crohn's disease;
3.29(9) terminal illness, with a probable life expectancy of under one year, if the illness
3.30or its treatment produces one or more of the following:
3.31(i) severe or chronic pain;
3.32(ii) nausea or severe vomiting; or
3.33(iii) cachexia or severe wasting; or
3.34(10) any other medical condition or its treatment approved by the commissioner.

A couple of issues about the statutory conditions.  First of all, a patient wanting to use cannabis for any of these conditions needs to be certified that they have the conditions.  That is not the same as a medical diagnosis.  Each patient will need to apply to the Department of Health for the certification and that will cost $200.  Physicians are not necessary for the patient to be certified.  Anyone certified and any physician who wants to be involved will be monitored in a registry through the Department of Health.  It is also obvious from the list, that for the conditions, there is really no known medical indication for cannabis.  An excellent example is glaucoma and the review of the pathophysiology and treatment for glaucoma for primary care doctors in this week's JAMA.  Finally, the entire system is going to be implemented as a research program with no controls and (so far) no known research methodology.

The newspaper headline touches on one of the main issues and that is the cannabis will not be smoked.  There was an initial consideration that vaporizers could be used in a physicians office under the supervision of a physician.  That restriction was not in the final bill.   The Commissioner of Health is charged with providing people certified for the following conditions with medical cannabis by July 1, 2015.  In the conference I attended today, there will apparently be competition for two suppliers to provide medical cannabis at 4 outlets each in the state.  Medical cannabis is defined as:

 (e) "Medical cannabis" means the flowers of any species of the genus cannabis plant,
1.20 or any mixture or preparation of them, including extracts and resins which contain a
1.21 chemical composition determined to likely be medically beneficial by the commissioner,
1.22 and that is delivered in the form of:
1.23 (1) liquid, including, but not limited to, oil;
1.24 (2) pill;
2.1 (3) vaporized delivery method with use of liquid or oil but which does not require
2.2 the use of dried leaves or plant form; or
2.3 (4) any other method approved by the commissioner but which shall not include
2.4 smoking.

That last two lines were were surprising, but law enforcement in Minnesota was apparently not on board with legalizing marijuana smoking.  Given the momentum of the marijuana movement at the national level, that was surprising to see in what is considered a liberal state.  The psychiatric society also gets credit for removing Post Traumatic Stress Disorder, from the list of qualifying medical conditions and providing the governor with a rationale to continue negotiating.

The Commissioner is also charged with reviewing the literature on medical cannabis, suggesting doses and additional qualifying medical conditions, and maintaining a registry of the effects of medical cannabis on the target condition.  That aspect of the law seems like a black hole to me, because it means that the Health Department will essentially be providing FDA services on an experimental medication.  What state department of health can pull that off?  The trials will all apparently be observational studies since no group of people wanted to be control subjects.  They apparently have no doubt that cannabis is an effective drug for what ails you.  Since cannabis has been used by humans since the Neolithic Era (4,000-2,500 BCE) and medicinally in many contexts since then, it is always interesting to consider why nobody has not found a consistent medical use in the past 5,000 years.

The Minnesota law is an interesting approach and I think it may be an excellent compromise.  It gets cannabis to the severely ill who claim benefits while avoiding the issue of recreational use.  This is also an an analogous approach currently used in the case of terminally ill patients and getting them access to experimental therapeutics.  According to speaker I was listening to yesterday the case presented by mothers of children with intractable seizures provided some of the most  compelling testimony.

The passage of this law also dovetails with the editorial in Science this week.  DuPont and Lieberman make the case that adolescent exposure to cannabis should be expected by any legalization and the long term effects on that population are really unknown, but that the preliminary evidence in terms of future risk of addiction or psychiatric disorders does not look good so far.  That same issue of Science has an interesting article on neurogenesis in the dentate gyrus at various points in the life cycle of mice pointing out that learning and retention requires a delicate balance in just the right amount of neurogenesis.  Preliminary research suggests that cannabis affects neurogenesis.

I don't often agree with the politicians of either party, but this may be the best compromise available during a cultural trend of increased permissiveness toward drug use.  The main problem with the bill is putting the Department of Health in a regulatory role that may be difficult for them to realize without a significant increase in budget and manpower.  It also makes cannabis seem to be a legitimate medical treatment - when it is not.


George Dawson, MD


References:

1.  Mike Cronin.  Minnesota Senate passes medical marijuana bill; could become only state that bans smoking.  Minneapolis StarTribune May 17, 2014.

2.  Information for S. F. No. 2470

3.  Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014 May 14;311(18):1901-11. doi: 10.1001/jama.2014.3192. PubMed PMID: 24825645.

4.  Mongiat LA, Schinder AF. Neuroscience. A price to pay for adult neurogenesis.  Science. 2014 May 9;344(6184):594-5. doi: 10.1126/science.1254236. PubMed PMID: 24812393.

5.  Akers KG, Martinez-Canabal A, Restivo L, Yiu AP, De Cristofaro A, Hsiang HL, Wheeler AL, Guskjolen A, Niibori Y, Shoji H, Ohira K, Richards BA, Miyakawa T, Josselyn SA, Frankland PW. Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science. 2014 May 9;344(6184):598-602. doi: 10.1126/science.1248903. PubMed PMID: 24812394.

Era of Blockbusters Is Over? I Hope So.

1BOM posted a link to a Forbes article on the issue of blockbuster drugs.  Journalists are typically slow to pick up on this because it takes the element of scandal out of any relationship between physicians and the pharmaceutical industry.  After all, aren't physicians clueless about pharmaceutical advertising and mindless cogs in Big Pharma's attempts at hegemony?  The tone of the article is that Big Pharma is now increasing the drug prices for therapies targeting fewer conditions.  No thanks to Big Pharma for all of the innovation currently used by the generic pharmaceutical companies.  As an example, I bought a bottle of montelukast (90 tablets) a month ago for $9.  It is the Singulair product list as Merck's 2010 blockbuster drug in the Forbes article.  As far as I can tell, it is the only effective treatment for an asthma attack that has caused me to take oral prednisone, inhaled glucocorticoids of various types, nebulizer treatments, inhaled ipratropium, and various inhaled beta agonists for the past four months.  I didn't see the US government or the academic community inventing montelukast.  In fact, I don't see the US government or the academic community doing much about the fact that the average asthmatic is still wheezing and there is no effective approach to preventing the spread of respiratory viruses that are a major cause of this problem.  I guess their solution is to partner with managed care and suggest that pay-for-performance is going to save us all.  Maximum treatment with everything except montelukast has done nothing for me.  What would pay-for-performance do?

Maybe that is why doctors who I have seen always ask:  "Are you sure you NEVER have smoked?" That seems to happen after the usual: "I like to treat asthmatics because I can do so much for them!"  If that is true why are most asthmatics still wheezing?  I think it is fair to say that the only reason I am wheezing less at this point is due to Merck.  The necessary CME disclosure at this point is that I do not own any pharmaceutical company stock, but I am quite willing to admit it when I see a good product defined as one that works for me.  Since the focus of this blog is on psychiatry - I also get direct feedback from patients that the medication I prescribe has had some of the same effects.  That is even in the case of medications that I never prescribe - paroxetine and fluoxetine, in people I see for consultation.  And for all of the clinical trials obsessed out there - I suppose I could just say or think: "I guess this person is unfamiliar with the meta-analyses critical of antidepressant efficacy." or at least: "I guess this person has never been on the Internet and read about the horrendous side effects of these medications."  But being the foolish psychiatrist I am, I am likely to think that a person with severe depression requiring hospitalization, severe postpartum depressions with psychosis and suicide attempts, or severe disabling depression may have actually found an effective medication that works for them.  I am much less impressed by the work of statisticians than the experience of my patients, especially when their lives are back on track.

In terms of the cost of psychiatric medications, this is really an old issue.  It was years ago when I noticed that people could pick up citalopram for $4 a month at Wal-Mart.  I had to point the wide availability of generic antidepressants in a response to a Washington Post article.  I guess the DSM-5/Big Pharma conspiracy is not looking too good now.   Sure there are new antidepressants, but there is no reason why they should be first line drugs.  Anyone with an first time PHQ-9 elevation is going to get an inexpensive SSRI.

All of the critics of Big Pharma were naturally slow to pick up on it, especially the antipsychiatry crowd because it means that the moral high ground is lost.  They can no longer devalue everything that psychiatrists do based on the alleged Big Pharma connection with a handful of psychiatrists.  Of course they can keep the conspiracy theories going about some missing clinical trial results of a now generic drug that is over thirty years old.  They can conflate that as having something to do with psychiatry despite the fact that the major regulators like the FDA have done nothing about the drug based on post marketing surveillance.  They  can blame psychiatry for the overprescribing of primary care physicians and the institutionalized overprescribing of managed care systems.  The antipsychiatrists will certainly continue to hate psychiatry and the critics will still have an axe to grind with particular psychiatrists. But at least I won't have to tolerate a smug blogger proclaiming that they were "Keeping psychiatry honest since 2007."  I have actually done very well maintaining my honesty without the help of a self promoting blog and the psychiatrists I know have done the same.

And wait a minute - what about the real epidemic that has been actually killing more than 10,000 people per year for over a decade?  Plenty of generics there and plenty of ways to take way too much acetaminophen.

The other problem with the Big Pharma conspiracy theories has been a general naivete about capitalism and marketing.  Advertising is good for the New York Times, but not a medical journal or meeting.  Physicians need to be cloistered from market influences.  They could be corrupted in a way that is inimical to the interests of patients.  Direct advertising of toxic medication to consumers is a much preferred route.  As far as the "me too drug" argument goes, let me illustrate the problem with that argument by my trip to the convenience store today.  I ran out of grape juice today.  I only drink Welch's 100% grape juice, diluted at a ratio of about 5:1 with carbonated water.  I drink about 576 fluid ounces of the stuff per month.  Rather than go to a supermarket, I went to a convenience store because it was closer.  On the shelf were a vast array of chemical drinks and sodas of no nutritional value, small bottles priced at what I could buy 64 ounces of pure unsweetened grape juice for.  The comparisons were overwhelming.  Self proclaimed nutritional drinks that had no calories, no protein, and plenty of artificial sweeteners.  Natural juice "beverages" or "cocktails" that had vanishingly low amounts of actual juice.  All of these products basically knock offs of fruit juice, but, heavily marketed, neatly packaged, much more expensive, and having the occasional nutrient value of added vitamins.   Does a "me too" pharmaceutical have less value than a "me too" soft drink?  There is no comparison.

I also had the association to my Peace Corps experience.  In the country where I served in Africa, there was a place called the Northern Frontier Zone.  There was a police outpost there and you had to sign a register acknowledging that the local government was not responsible for your safety once you crossed into that territory.  One of the best ways to get there was to hitchhike on large trucks carrying Coca-Cola.  You just had to get comfortable laying on cases of Coke.  Over the years,  I have drank as much Coke as anybody - but for the purposes of this post and the focus on advertising and marketing consider what I am saying here.  In 1975, Coke was widely available in remote African villages and the Northern Frontier zone.  For most people it was more widely available than clean water.  Since then. they have sold increasing amounts of the product.  The world is dominated by American cola manufacturers.  Are "me too" pharmaceutical products less valuable than Coca-Cola?  I would suggest that they are probably not and they are marketed a lot less vigorously.  Unless I have missed it there has been no complaint about Coke's world domination, although I sincerely hope that a psychiatrist is never photographed drinking a can.

I might be biased by a good four months of decreased wheezing, but I hope the general message on the Forbes article gets out and clears some of the air.  In psychiatry, there are many more important things to focus on than conspiracy theories that really don't apply to the vast majority of psychiatrists.  You can't take physicians out of their historical mandarin role and instead blame them for colluding with Big Pharma.  It may have been a political strategy to get them out of that role and suggest that politicians (of all people) should assume that role.

The work psychiatrists do is tough and demanding.  No psychiatrist who I have ever talked with expects a pat on the back.

Getting out of our face is a pretty modest wish.

George Dawson, MD, DFAPA

Supplementary 1:  I also have no financial interest in any of the other products mentioned here including Welch's grape juice or Coca-Cola.  I used the real names because they are historically accurate.

The Spectrum Of Caring About Medication Information

With over half of Americans on prescription drugs and many on significant polypharmacy, not a lot is known about the decisions to take a medication or the associated informed consent issues.  There is always a question about whether a productivity based, low quality medical environment will result in more prescriptions or less.  There is the ever present marketing issue and regulatory decisions by the FDA that often seem to be market based.  The CDC came out with recent data on this phenomenon today including some excellent information on potential overprescribing - see the antidepressant and antibiotic slides (click to enlarge any graphic).

I thought I would look at how medication information seems to be used by patients.  I  try to condense this issue down to a graphic to capture what I think are the essential elements to consider in terms of the information requirements that people need to make decisions about medications.  There is a full spectrum of considerations from people who don't want to know anything about a medication to those who want as close to a medical level of knowledge as possible.  The one area of this table that I know for certain is that we all start out in a common place and that is not wanting to take a medication at all.   As I have pointed out here several times, searching for a medication that will work for a problem is often fueled by desperation.  Medication side effects and a lack of efficacy of medications is common.   The graphic is based on my direct observations about medications and how people decide that they will use them.  I eliminated the scenarios that involve addiction for the purpose of a more simplified scenario, but could develop that if anyone is interested. (click to enlarge)

In 30 years of practice I have encountered all of the scenarios listed in the above table at one point or another.  As an intern on the Internal Medicine service, I recall a young man who I had just admitted to the ICU for acute asthma.  We gave him the usual glucocorticoids, theophylline, and albuterol nebulizers.  Within and hour he wanted to leave.  His respiratory status was slightly improved at the time but my resident, attending, and I did not think it was a good idea.  He signed out AMA with the complaint that is was just too boring to stay in a hospital despite his flare up of asthma and continuou wheezing.

I have also had plenty of experience at the other end of the spectrum.  They are generally complicated situations involving treating physicians or other professionals or the relatives of professionals, people with severe complicated problems that have not responded to any of the usual therapies, people taking highly interactive or toxic medications, or people with personality structures (innate or acquired) that require a lot of information or the idea that better decisions are predicated on the maximum amount of information.  Many of these folks also have ideas about physicians and expectations of how much time they are able to spend with physicians.  

If I had to guess about the distribution of people I have talked with most of them would probably lie in column 5 (from the left).  The distribution of people on both ends of the table is low.  I think that the most important aspect of this spectrum for a physician is recognizing the approach that the patient is taking and trying to complement that.  That involves being more available to people who don't want a lot of information up front in the event that they have experiences with the medication that they might want to ask about.  Even in the case of refusal of medication, people change their mind especially when dealing with illnesses that are clearly disruptive and potentially life-threatening.  Some people may come back and demand to know why nobody forced them to take a medication in the first place even when they refused it initially.  

Television ads for new medications seem to take a high pressure approach to column 6 with a very rapid speech about severe and potentially life threatening complications.  The ads obviously lack depth for the person described in this column, but they have a degree of transparency about severe effects.  I would wonder if a person speaking more slowly about the side effects would have more impact.

The other lesson that is often lost is that there is no correct way to consider information for an informed consent decision about medication.  Physicians consider rational thinkers to look at the probabilities of the risks versus the benefits and make a decisions.  That is what much of the medication information educational material is based on.  In fact, medication decisions are very personalized.  The response of the population in general does not dictate the response of the individual.  The affected person may have no interest at all in a new medication that is offered but they may recall detailed information about their response or the response of their family members to medications.  They may also have had very adverse experiences with medications, physicians, and other medical personnel.  People develop medical comorbidities at different rates and that will also be an important aspect of the decision making process.  The only decision-maker who is really problematic in this table is a person who takes an empirical approach and then does not report any side effects thinking that they will "get used to" the medication.  I think a lot of those ideas may originate with physicians who have inflexible approaches because in my experience people rarely get used to side effects and some side effects are harbingers of potentially severe problems.

There are also important questions about the overprescribing issue.  In at least some of those cases, physicians are often dealing with patients who may be receiving information like: "You don't have signs of a bacterial infection" but processing it as: "I believe in antibiotics and need to take antibiotics to get better".  

I think this is all an important aspect of the informed consent process.  The informational aspects of informed consent need to include how much information a person is willing to consider is the first step.  The analysis of that data follows.

George Dawson, MD, DFAPA 

Near Riot In A 24 Hour Pharmacy

This is a true story.

Not too many years ago, my father-in-law and mother-in-law came to town for Thanksgiving.  They had to drive about 6 hours to get here and in their haste to leave town, they forgot some of their medications.  We were able to get the scripts filled at a 24 hour pharmacy, but the pharmacist said: "You can come down and wait - but it will take a while."  I drove down around midnight and there were about 15 people standing there.  "Not too bad I thought" and took a seat.  Over the next 30 minutes the crowd started to build.  This was the Wednesday night before Thanksgiving, but we were already into Thursday.  I could see the pharmacist and noted he was a PharmD.  He was also working furiously.  He was literally filling prescriptions at the rate of 1 - 2 every 5 minutes while taking telephone calls.  I noticed at the 30 minute mark he was starting to break a sweat.  The next time I looked up there were over a hundred people there, pushing back through the aisles.

The pharmacist's work ethic was not enough to appease the crowd and it was getting ugly.  It started out with the kind of atmosphere you find on an airplane when a passenger does something to delay take-off.  A lot of irritable people grumbling under their breath and rolling their eyes for the most part, but the occasional well enunciated expletive.  "Great" I thought: "Here is a guy who has a PharmD working as fast as anyone can work and it is not fast enough for the growing mob."  To make matters worse, a very crabby middle-aged women sat down right next to me.  As the crowd got angrier, she started to ridicule them.  It was hard to believe at first, but she would lean over to me like we were best friends and make incredibly crude remarks at the people in the front of the crowd.  Even though she leaned toward me, she projected her statements right at the front row.  I thought about whether I should intervene and talk with her but instead, I just dissociated and hoped that my prescription would come up soon and I could get out of there.  Besides, the angry young men in the crowd had already made the decision that there was probably nothing to be gained from arguing with an irritable middle-aged woman much less pummeling her.

I thought back to the pharmacists I knew well.  Working mostly in a hospital setting you get to know a lot of pharmacists.  They are a critical part of just about very level of care that involves medications.  They participate in Pharmacy and Therapeutics (P&T) Committees and provide most of the hard data for discussion.  They sign off on all physician orders and call that physician if there is a problem.  They provide education for physicians, patients, and nursing staff.  These days they monitor and change the orders on warfarin and some antibiotic therapies and do the phrmacokinetics.  In many cases they work with Infectious Disease teams on monitoring antibiotic and fungal resistance as well as antibiotic selection for drug resistant bacterial infections.  They used to work in teams with inpatient units and discuss drug interactions and pharmacokinetics.  For years they would come in person to my unit to trouble shoot all things in person on my unit every day.

At least until managed care decided that pharmacists should just crank out prescriptions.  Clinical pharmacists disappeared from their consulting roles.  Initially just a few units.  We still had a pharmacist to consult with, but eventually that person (who specialized in psychopharmacology) also disappeared.  I would drop by the pharmacy to pick up scripts and see my old colleagues all working furiously - just like the PharmD I was watching through the window in the 24 Hour Pharmacy.  They were so busy filling prescriptions they barely had time to look up.

For anyone who thinks that only physicians have been marginalized by the management that goes along with managed care, it really goes across the board.  Pharmacists, nurses, and clerical workers are all put on the same production plan.  I always wonder how we survived doing things in a collegial manner before all of the management geniuses showed up.  Is it an artifact of managed  care that there now seem to be billions of prescriptions more than before we were in a managed care environment?  Is it the logical outcome of of widget production?  The prescriptions in the 1980s all got filled and I still talked with the clinical pharmacists in person every day.  There were no near riots in the pharmacy.  When physicians and pharmacists are talking and networking - the quality of care is better.  As an interesting sidebar, I consulted my most recent text on management of healthcare systems (copyright 2008) and there was no mention of pharmacy services or pharmacists, but plenty of references to the pharmaceutical industry.

Back to the all night pharmacy.  My name was finally called and it was not a moment too soon.  The woman in the seat next to me had just made a loud and incredibly crude remark to the mob.  Several people had noticed and seemed ready to say something.  I turned to her and said:

 "If I told you that you had to be cool would you know what I meant."
"Yeah - I suppose so"
"Well good because you really need to be cool here.  You are starting to make some of those people angry and they are already angry about waiting at 1AM to pick up prescriptions."

I picked up my prescription and left.  As far as I know there were no further incidents.  At least I did not read about anything in the papers.

I was burned out from my job at the time.  I think I was covering an entire 20 bed inpatient unit.  I had taken a week off to recover.

But I was very glad to not be a pharmacist.

George Dawson, MD, DFAPA