Addiction and ADHD - The Bullet Points

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

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

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

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

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

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

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

George Dawson, MD, DFAPA



References:

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

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

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

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

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

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


Attribution:

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

Placebo - Nocebo Implications For Psychiatric Research and Clinical Care

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

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

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

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

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

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

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

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

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




George Dawson, MD, DFAPA


References:

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

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

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

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


Attribution:

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

Lancet Psychiatry's Inconsistent Look At Conflict Of Interest

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

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

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

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

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

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

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

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

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

George Dawson, MD, DFAPA

Ref:

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

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

Robust Doses of Extended-Release Mixed Amphetamine Salts To Treat Cocaine Use Disorder

JAMA Psychiatry. 2015 Jun 1;72(6):593-602

This article (2) caught my eye in JAMA Psychiatry.  Stimulant (methamphetamine, cocaine, prescription stimulants, and various synthetics) use disorders (previously called addictions) are difficult problems to treat.  That is especially true because of the epidemic of adult Attention Deficit~Hyperactivity Disorder diagnoses and the cross contamination from the cognitive enhancement movement as well as new indications for stimulant prescriptions.   Stimulant medications are widely available and generally work at some level for most people who take them leading to the common impression that:  "I took my cousin's Adderall and it worked!  Therefore I must have ADHD and need my own Adderall prescription."  By the time that has happened it is usually very difficult for any physician to explain to this patient why a positive response to a stimulant does not equate to an ADHD diagnosis, especially if the prospective patient has been functioning at a high level and is presenting for diagnosis and treatment after doing extremely well in college and their first few years of professional school.

A second problem with the ADHD stimulant use issue is the misconception that people with "true" ADHD are less susceptible to the positive reinforcing effects of stimulants than people without ADHD.  There are certainly subgroups of person with this diagnosis that do not like to take stimulants.  They find that stimulants decrease their appetite, given them increased anxiety and insomnia, and in many cases leave them feeling more restricted, affectively blunted and less spontaneous.  I find that these patients are generally selected out by the time they are adults.  They had true ADHD diagnoses in middle school, did not like the stimulants, or in many cases their parents did not like the effect they were seeing and they were taken off of them.  They may have developed significant coping strategies based on their dislike of stimulant effects.  Like many adult psychiatric disorders there is no one uniform phenotype, and the phenotype of the person who was diagnosed either as a child or an adult and who gets a euphorigenic effect from stimulants and escalates the dose clearly exists and is seen in treatment centers.  In many cases they have an iatrogenic diagnosis of bipolar disorder from a pattern of taking the month's prescription of stimulant in the first one or two weeks and then either going into withdrawal or using a depressant like alcohol, benzodiazepines, or opioids to treat the dysphoria and cravings associated with stimulant withdrawal.

There is also the situation where a person has been using high dose prescribed stimulants (taking more than prescribed) or using high doses of meth or cocaine off the street, where they develop a residual state that is identical to ADHD, but where the cause of the ADHD is the stimulant.  I think it is an error to treat that residual state with stimulants.  That residual state is generally associated with a profound level of impairment and lack of insight.  The patient is aware of significant cognitive problems, attributes them to ADHD and often insists on treatment with stimulants despite a clear addiction to stimulants.  They may insist that years or decades of stimulant use was their attempt to self diagnose and treat their own ADHD.  It is very common for patients with substance abuse problems to give a history of no formal diagnosis in childhood, no school or occupational impairment, but to offer the opinion that they think they may have ADHD.  All of these considerations lead to associated problems in providing care to people who have clear ADHD and stimulant use diagnoses.  

That leads me to this multisite study (2) on the effects of high doses of extended release mixed amphetamine (ER MA) salts on both ADHD and cocaine use in patients who have both of these diagnoses.  The doses used were 60 and 80 mg/day.  The most commonly used current prescription versions of these drugs typically recommend a maximum dose in adults of 30 mg/day (1), but interestingly there is a "titrate to tolerability" statement in the package insert of a drug where 20 - 60 mg/day were used in trials with the statement  "There was not adequate evidence that doses greater than 20 mg/day conferred additional benefit."  The authors describe their dosing selections as "robust" and suggest that there is evidence that higher doses are needed to treat cocaine use problems.

Looking at authors methodology, their screening for this trial is instructive of the problems encountered in clinical practice.  Of a total of 1614 patients screened, only 126 were ultimately randomized to placebo, 60 mg/day ER MA, or 80 mg/day ER MA.  Five hundred and sixty two were screened out due to medical or psychiatric exclusion criteria.  It is common in older populations of stimulant users to find significant cardiovascular morbidity in the form of cardiomyopathy, coronary artery disease, and arrhythmias and these were some of the exclusion criteria.  The other aspect of this study that I really liked and would suggest implemented in everyday practice is the authors approach to blood pressure and heart rate specifically:

"Participants with blood pressure higher than 140/90 mm Hg or heart rate higher than 100 beats/min for 2 weeks or with single readings of blood pressure higher than 160/110mmHg or heart rate higher than 110 beats/min were discontinued from study medication." 

It is always shocking to hear from a person who has been on stimulants for years that nobody has ever checked their blood pressure or pulse, especially when they are sitting in front of you and are hypertensive and tachycardic.  This basic procedure should be done on any person taking stimulants, antipsychotics, antidepressant and for that matter any CNS active drug.  If similar effects are noted with any of these medications they should be discontinued.

Another important aspect of this study is that although the patients were well screened, they were complex from a substance use standpoint with current alcohol (18.6 - 27.9%), cannabis (7 - 14%), and nicotine (45-65.1%) use disorders.  The high levels of nicotine use are not surprising considering the epidemiological correlations between smoking and cocaine use and recent evidence about the epigenetic effects of nicotine in substance use disorders.  The authors do not comment on whether there were different outcomes for the non-smokers in this study.

On the primary outcome measure for ADHD - a 30% reduction in the AISRS (Adult ADHD Investigator Symptom Rating Scale) 58.1% of the high strength group and 75% of the low strength group achieved that outcomes with odds ratios of 2.27 and 5.23 respectively (see text for confidence intervals).  In terms of cocaine use outcomes the 80 mg dose resulted in fewer cocaine positive weeks (by any positive toxicology or report) and abstinence in the last three weeks.  The numbers are given in the table below:

High dose MA ER resulted in both a significant reduction in cocaine positive weeks over the 14 weeks of the study.  The 60 and 80 mg doses were actually fairly equivalent form a statistical standpoint and both were superior to placebo in terms of ADHD and cocaine outcomes.  But the real question is whether this is a reasonable clinical approach to this problem?  This was an intent-to-treat analysis with significant drop out rates.  The drop out rates are illustrated in the rapid decline in denominators in each group in Table 2.

In my experience, a substantial number of patients with ADHD and either cocaine or amphetamine use disorder reach the end of the prescribing algorithm where they have failed or relapsed.  In many cases that failure does not lead to a prescription being stopped for many reasons, a lack of information to the prescribing physician being foremost among them.  In the real world there is no clinic that will follow patients three times a week with toxicology screens at most of those visits and offer them all cognitive behavioral therapy.  Models currently funded by managed care companies and governments consist of patients being seen every one to three months for 20 or 30 minutes.  Many of those  visits are done by clinicians with little to no addiction experience.  Within the medication maintenance literature, particularly with buprenorphine maintenance there are studies that suggest psychotherapy adds nothing to the outcomes.  But even without that data what business manager would consider those therapists "cost effective" beyond the stimulant prescription?

A key element that I never see in these studies is the patient's subjective response to the stimulant at increasing doses.    I have found that Koob's definition of addiction is generally predictive:

"Addiction is a chronic relapsing syndrome that moves from an impulse control disorder involving positive reinforcement to a compulsive disorder involving negative reinforcement."

A euphorigenic, hypomanic effect is usually the high risk positive reinforcer regardless of the substance taken.  One of the theories of abuse deterrent approaches is that the pharmacokinetics of the substance used prevents rapid availability in the brain and this decreases abuse potential.  Many abuse deterrent preparations fail because multiples of the dose can be taken and result in the positive reinforcing aspects of the addiction cycle.  I consider the authors' paper to be elegant in its experimental approach.  The graphic at the top of this page is first-rate as a source of information.  It also illustrates the problem of coming up with a clinical trial that can be translated into practice.  I would not consider implementing this strategy as a clinical approach until there was a long term study that looked thoroughly at all of the outcomes.  At this time, I don't think the modest results of this short term study warrant the widespread practice of using extended release mixed amphetamine salts for cocaine use disorders.  There are also legal issues with prescribing maintenance doses of controlled substances in order to "maintain an addiction" as some laws are currently written.  I would have liked to see an attempt to characterize the subjective responses to methamphetamine use measured along with an analysis of whether the non-smokers did better than the smokers.

George Dawson, MD, DFAPA



References:

1:  Drug Facts and Comparisons.  Wolters Kluwer Health.  St. Louis, MO, 2013.

2: Levin FR, Mariani JJ, Specker S, Mooney M, Mahony A, Brooks DJ, Babb D, Bai Y,Eberly LE, Nunes EV, Grabowski J. Extended-Release Mixed Amphetamine Salts vs Placebo for Comorbid Adult Attention-Deficit/Hyperactivity Disorder and Cocaine Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2015 Jun 1;72(6):593-602. doi: 10.1001/jamapsychiatry.2015.41. PubMed PMID: 25887096; PubMed Central PMCID: PMC4456227

Attribution:

1.  The figure at the top of this post is from reference 2 above and is used with permission from the American Medical Association, License Number 3660331303348.  Copyright © 2015 American Medical Association.  All rights reserved.

Johnny Cash On Doctors And Chronic Pain

Driving home on a Friday night, as usual I am listening to public radio.  This time I happened to catch an interview with the late Johnny Cash.  Many people are not familiar with how much pain he endured over the course of his life, especially toward the end.  His problems with drug addiction are better known and that combination of chronic pain and drug addiction is a dangerous one.   I found a photo of Cash on Flickr that was taken by a photographer who encountered him when he had significant pain and I am currently trying to get permission to post that photo at the top of this essay.  The years of pain and illness appear to have taken a toll in this portrait and he looks weary.  I heard him commenting in a radio interview on the PBS series Blank on Blank.  After and introduction that describes him as having severe constant pain in his left jaw and the statement that he cannot take pain medications, the interviewer Barney Hoskins suggests that he is brave and Cash replies (1):

Johnny Cash: "No. I’m not very brave because for five years I didn’t try to take the pain.  I fought it.  I had a total of 34 surgical procedures on my left jaw.  Every doctor I’ve been to knows what to do next, too.  To relieve me of pain, I don’t believe any of them.  I’m handling it.  It’s my pain.  I’m not being brave either.  I’m not brave at all after what I’ve been through, I just know how to handle it."

That is hard fought wisdom when it comes to dealing with chronic pain.  In the previous few lines Cash had explained why he could not take pain medications.  He described it being like an alcoholic not being able to drink alcohol.  His pain started when his jaw fractured during a dental procedure and never healed appropriately.  In Hilburn's biography (2), Merle Haggard is quoted as saying that Cash was at a chronic 8/10 level, using the typical 10 point pain scale for the last 8 years of his life.  It is difficult to imagine how hard it might be to try to sing with chronic jaw pain.

Managing chronic pain in a person with a significant addiction problem is one of the most challenging areas of medicine.   For the past 15 years, the USA has been in the midst of an epidemic of opioid painkiller use and accidental overdose deaths.  This has been largely due to the effects of the politicalization of pain and pain medications starting with initiatives to prescribe more opioid pain medications for chronic pain and for acute indications that previously may not have resulted in that kind of a prescription.  From what I can tell, the liberalization of opioid prescribing came about initially as the result of initiatives from the Joint Commission (JCAHO), the Veteran's Administration, and the American Pain Society.  The initiatives can be viewed on this timeline. 

The treatment of chronic pain is also viewed as a treatment that involves multiple modalities.  It can certainly involve the use of various forms of pain medication, but physical therapy and psychological therapies are also mainstays of treatment.  I have consulted in many situations where patients have had multiple surgical interventions for pain that have not been effective.  I have never seen a person with 34 surgical procedures for the same pain.   From a purely medical perspective, the treatment can involve opioid medications, but also gabapentin, pregabalin, and various antidepressants.  Chronic pain is frequently associated with insomnia, anxiety, and depression and additional medical or psychological interventions for these problems is useful.  Many people have strong biases about opioid medications and consider them to be the ultimate treatment for pain.  Double blind, placebo controlled studies show that for neuropathic pain, the relief is moderate and generally equivalent to non-opioids.  Unfortunately for many, that fact is not known until after the person has become addicted to the opioid.

The surgical approach to pain is gradually changing over time.  I did a lot of neurosurgery during medical school rotations and in those days, there was a definite prosurgical approach to back and neck pain.  Imaging studies were more primitive with a predominance of CT versus MRI imaging of the spine.  I observed a lot of laminectomies and posterolateral fusions, using bone graft from a rib or iliac crest.  I was also in the clinic and saw large numbers of patients coming back over time for chronic opioid prescriptions for continued pain that failed to clear up with the operative procedure.  Our standard prescription in those days was Darvocet N-100s,  a fairly low potency opioid analgesic that also contained acetaminophen.  It was voluntarily withdrawn from the market by the manufacturer in 2010 after this labeling revision by the FDA in 2009 highlighting the risk of overdose, cardiac conduction abnormalities and fatal arrhythmias.  In the course of psychiatric practice, I pay close attention to spinal problems.  Spinal injuries are surprisingly common.  Degenerative disease of the spine is also common and there is very little focus on spinal health and the prevention of these problems.  In the people I have seen over the years, good prognosis spinal surgery in terms of pain relief generally involves a well defined lesion and neurological deficit in addition to the acute pain.  Chronic unchanged pain is still an outcome after repeated surgery.  At that point the question becomes, is there any medication that will reduce the level of pain.   Some people will do well with chronic opioids, but the problem is that patients with addiction generally do worse and exposing more and more people to opioids is increasing the number of people with addictions.  SAMHSA suggests the algorithmic approach in Exhibit 3-1 (3) above.  The problem is that there is no good data for relapse, failure, or success rates after trying an opioid for chronic pain in a person with an addiction.  My experience suggests that relapse rates are very high and success rates are very low, but I am seeing a population with a very high rate of addictions
         

In the absence of any markers of opioid addiction liability or reliable interview approaches a conservative approach is required and an extremely cautious approach is required if the patient has a known addiction problem.  The comment on doctors by Johnny Cash is one that is best not forgotten.  One of the reasons that opioids are prescribed in the first place is that pain is chronic and refractory to usual treatments.  In some cases, years of trying multiple opioids and going through residential drug treatment centers has resulted in the perpetuation of chronic addiction and chronic pain.  The algorithm above suggests the appropriate course of action for patients with that problem.  They need to be tapered off the pain medication and typically maintain the medication is necessary.  In many cases there is a significant amount of pain relief and improved function by tapering and discontinuing the opioids.  In some cases, the ability to function improves because the addiction fades away even though the pain is no better.

Johnny Cash got to the point where he could be tapered off the opioids and make it on his own.   That is a tough goal, but one that more people should strive for at least until there is a better solution to chronic pain and addiction.  He also reminds us of the role of physicians in this process.  My overall impression is that there are more physicians willing to draw the line and say: "I really don't think that another operation or medication is going to add much to what you have already tried." ..... but I don't think there is a lot of evidence to back up my opinion.      

George Dawson, MD, DFAPA

References:

1:  Barney Hoskins.  Johnny Cash on the Gospel.  Blank On Blank.  October 1996. 

2:  Robert Hilburn.  Johnny Cash - The Life.  Little, Brown, and Company.  New York. 2013. 

3:  Substance Abuse and Mental Health Services Administration.  Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders.  Treatment Improvement Protocol (TIP) Series 54.  HHS Publication No. (SMA) 12-4671.  Rockville, MD: Substance Abuse and Mental Health Services Administration, 2011. (Figure 3-1 above is from page 34 of this manual).

Will Sitting Really Kill You?

This question should strike fear into the hearts of psychiatrists everywhere.  We do after all spend practically all day sitting.  I easily spend 8-10 hours, 5 days a week sitting in a chair and another 5 or 6 hours on the weekend.  Not all of that time is as comfortable as it sounds, but it certainly does not require a great deal of physical exertion.  This situation only got worse with the placement of computer terminals in every office.  When I first started working, I would walk down the hallway and randomly glance into office doors.  In order to look busy, the people in those offices would typically stare at a paper or papers on the desk or in their hands.  Now everyone is staring at the obligatory computer screen.  I won't digress into the massive problems associated with the computerized model but only point out how people have been immobilized by it.

Several years ago, I started to see stories about people who were exercising while they did their work.  I remember the first story showed an office where the person at the desk lost a significant amount of weight by walking on a 1 mph treadmill while he worked the phones and used his computer.  That was followed by the idea that it was healthier to stand all day than sit.  Suddenly there were people in my clinic standing at work instead of sitting.  And then I started to see the news stories suggesting that it was dangerous for person to sit at work.  Sitting at work could actually lead to a shorter life.  It could kill you.   They were the type of news stories that lead you to an immediate search of your memories to see if this could possibly be true.  Does it have face validity?  Has there been a hidden epidemic of deaths due to - (gasp) sitting.  I rapidly dismissed the idea as a combination of marketing and hysteria.  But the stories persisted.  There was an article from a reputable clinic that described how enzyme activation changed from the sitting to the standing position and that this had an effect on metabolism.  The usual concept for public consumption is that higher metabolic rates lead to more calories burned and weight loss.  It appeals to the American obsessions with calories, food, appearance, and weight loss.  Is there an easy way to trick the metabolism into burning off all of those calories I ate today?  Is there a hack?  Is it as easy as standing up at work all day?

I decided take a two pronged approach to look at this problem - review the whole idea of activity monitoring and examine the available literature.  The following graphic is the display of a Garmin vivofit2 activity tracker.  This tracker plots all activity in terms of steps.  If you are walking too slowly it does not count those steps.  During the setup phase it asks you to select a fitness level and it plots the number of steps per day based on the level you choose and your height and weight.  I chose the level at the 75% percentile or about 7500 steps per day.  So far it has not been much of a problem doing that especially because I work on a campus that requires a fair amount of walking.  The step plot only tells part of the story, because I also cycled 19 miles today, but that is not really indicated in the hour to hour plots - only steps.

Notice the red zones below the graphs.  The tracker emits a soft beeping sound and an extending red bar across the display if you have been "idle" for an hour.  You have to get up and expend about 200 steps to cancel the visual alarm.  The overriding question is whether a warning for inactivity is valid, especially in the case of a guy who just biked 19 miles the same day.  The graphic of that cycling is illustrated below.

It may not be readily apparent but during the time I was cycling, the activity monitor went into a mysterious mode of counting steps.  Not nearly enough to account for covering 19 miles, but it did put a green mark below the line indicating a high activity period.

I make a great example of the immobilized white collar worker who counters that problem with a lot of exercise away from work.  But I go into the endeavor with my eyes wide open.   I can see it now - the guy who thought he was going to live longer than anyone else.  I have already experienced this attitude.  One day I was walking down the hallway eating a granola bar and and one of my colleagues came up to me and said: "Do you think you are going to live longer than me?"  He was using the Socratic method to get at my unconscious motivations for eating a granola bar.  I tried to emphasize to him that sometimes a granola bar is just that and some people like me happen to like the way they taste.  But he wasn't buying that idea.

So if I do keel over, I apologize in advance to my widow and hope that my family will understand  that I present this data with the best of intentions.  I think that it is good data because it involves actual measurements rather than the usual epidemiological data that most of these studies provide.  I have been sitting behind a desk for at least 6 hours a day over the past 35 years.  In that time, I have had 4 exercise stress tests (one was a stress echocardiogram) and a CT scan of the heart.  All of them were negative.  On the CT scan of the heart my calcium score was 0.  For the first 20 years of that period, I was cycling about 200-250 miles per week between the months of May and October and either riding the equivalent time on an indoor trainer or speedskating the rest of the year.  The last ten years, the mileage figure has gone down to 100-150 miles per week with additional strength training.

What about the new sedentary science?  The early data is well summarized in a 2011 review by Proper, et al (2).  The authors reviewed the quality of the evidence and concluded that the evidence is strong for all-cause and cardiovascular mortality, moderate for diabetes mellitus Type 2, and poor for body weight/BMI, obesity, waist circumference, and endometrial cancer.  A very detailed epidemiological study (1) of five different categories of sitting time was very interesting because it showed a correlation of sitting time dose on mortality and it showed that effect persisted even if controlled for BMI, smoking status, and activity level when not sitting.  Suggested mechanisms included lipoprotein lipase activity and the effect of being sedentary on cardiac stroke volume and output.  The effect on lipoprotein lipase activity was not trivial with one study showing that activity restriction resulted in a 10 fold elevation decrease of lipoprotein lipase activity in red oxidative muscle fibers.   Subsequent studies show that breaking up sitting time has the expected positive effects on metabolic markers including triglycerides, waist circumference, and fasting blood glucose.  Some recent studies have looked at measures of endothelial function (3) and demonstrated that there is a measurable decline with 3 hours of sitting that can be countered by walking for 5 minutes at 2 mph every hour.  If replicated that has important implications for office workers who think they need to stand or walk on a treadmill continuously in order to prevent the problems associated with a sedentary work environment.  It also has implications for the kinds of exercise that we recommend to patients for prevention of metabolic syndrome and cardiovascular disease.  Although I am aware of no clear guidelines it may mean at some point that our sedentary patients may just need to get up and move around in a low intensity manner on an hourly basis and plan a more high intensity exercise at least once a day.  It also has implications for the patients we see who have not been moving much and have significantly abnormal lipids profiles like people who are admitted to hospitals and residential treatment centers who have been immobilized for weeks or months.  It may mean that medical therapy for dyslipidemia is not necessary until the patient is up and moving about for a while.  It may also have implications for the cognitive dysfunction noted with many psychiatric diagnoses.  In the past year I saw Roger S. McIntyre, MD present data on cognitive problems in bipolar disorder and major depression patients that were correlated with obesity and metabolic syndrome (5).  Impaired executive function persisted during periods of euthymia.  Interventions that impact those metabolic factors may have an effect in improving cognition.   A more recent review takes a look at the variables that may be important in the types of exercise used to break up prolonged sitting times (4).

  
My preliminary take on all of this data is that sitting may be dangerous to your health, especially if your BMI is high and you have other risk factors.  In many of these studies the effect size of sitting seem relatively robust independent of other risk factors.  The measurements of rapidly deteriorating endothelial function over a period of hours raises a lot of questions.  For example, most people are going to be sleeping at least 7 hours per night.  Is there the equivalent amount of deterioration over that time period, or are there protective mechanisms during sleep that prevent that problem.  The 2001 review classifies sleep as a sedentary behavior that does not raise energy level substantially above rest.  And what about the idea that these periods need to be broken up by low level exercise every hour?   What are the optimal times and exercises for doing this?  The validation studies for these measures seem daunting.  And finally what about the technology.  It is obvious from what I have posted here that it is at a primitive stage.  Different manufacturers are marketing different features.  One manufacturer has a device that claims to wake you up in non-REM sleep in the morning.   I chose my device as the only one that has a one year battery life.   Practically every other equivalent fitness monitor battery lasted from 4-30 days.  I could use a monitor that tracks more than steps.  My guess is that my current device picks up some other accelerations based on the fact that it characterized my 20 mile bike ride as "high activity" but gave me a negligible number of steps.  It also needs to do a better job detecting sleep instead of using my specified sleep hours as a way to not count inactivity.  The best example of that is my attempts to catch up on sleep on Saturday and Sunday mornings being counted as inactivity.  And finally, if I am logging into a manufacturer's web site to log activity on all of the devices I have purchased,  that interface  should do a good job of integrating all of that data in a logical manner and showing the relevant scientific parameters.  A few references would not hurt.  I understand that a move to using software on your personal computer is a step away from the domination of internet cloud enamored device companies but I can't imagine there is not a market for that and the best possible display of data.

All things considered, it looks like there might be something here.  One of my colleagues stated her opinion that these devices might be useful for people who don't do much exercise.  But is there is a separate effect of being sedentary on your metabolism that prevents you from getting all of the effects of high intensity exercise?  There are reports of long time endurance athletes and high intensity athletes either sustaining heart attacks or having clear coronary artery disease at angiography.  A basic study that I could not find was the effect of interrupted sitting on lipid profiles and BMI.  That would be a difficult study to do because of the effort it would take in a community sample.

For now, I will add activity monitoring to my other exercise routines and see what I can learn from it.


George Dawson, MD, DFAPA


References:

1:  Katzmarzyk PT, Church TS, Craig CL, Bouchard C. Sitting time and mortality from all causes, cardiovascular disease, and cancer. Med Sci Sports Exerc. 2009 May;41(5):998-1005. doi: 10.1249/MSS.0b013e3181930355. PubMed PMID: 19346988.

2:  Proper KI, Singh AS, van Mechelen W, Chinapaw MJ. Sedentary behaviors and health outcomes among adults: a systematic review of prospective studies. Am J Prev Med. 2011 Feb;40(2):174-82. doi: 10.1016/j.amepre.2010.10.015. Review. PubMed PMID: 21238866.

3:  Thosar SS, Bielko SL, Mather KJ, Johnston JD, Wallace JP. Effect of prolonged sitting and breaks in sitting time on endothelial function. Med Sci Sports Exerc. 2015 Apr;47(4):843-9. doi: 10.1249/MSS.0000000000000479. PubMed PMID: 25137367.

4:  Benatti FB, Ried-Larsen M.  The effects of breaking up prolonged sitting time: a review of experimental studies.  Med Sci Sports Exerc. 2015 February 4, 2015, published ahead of print.

5:  Bengesser SA, Lackner N, Birner A, Fellendorf FT, Platzer M, Mitteregger A, Unterweger R, Reininghaus B, Mangge H, Wallner-Liebmann SJ, Zelzer S, Fuchs D, McIntyre RS, Kapfhammer HP, Reininghaus EZ. Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder-Gender and obesity effects. J Affect Disord. 2014 Oct 22;172C:367-374. doi: 10.1016/j.jad.2014.10.014. [Epub ahead of print] PubMed PMID: 25451439.

Attribution:

The chair photo at the top of this post is by Humanscale (shop.humanscale.com) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons.

Schizoaffective Disorder and Surfing Music

I will disclose my biases on schizoaffective disorder from the outset.  My decades of acute care experience suggests that it is a lot less common than suggested by medical records.  Reflecting on the unique experience of seeing people hospitalized many times over the course of 20 years, the most frequent pattern I observed was clear cut bipolar disorder turning into a diagnosis of schizoaffective disorder or in some cases "bipolar disorder and schizophrenia".  Since I worked at this hospital long enough and had the memories of my enthusiastic young psychiatrist self and my compulsive documentation to count on, I can say that the most frequent pattern was patients presenting with manic episodes turning to the less specific diagnosis.  Most of these people were in their 20s or 30s when they experienced a clear cut manic episode.  There was no doubt about it because of the rapid onset and mood congruent psychotic symptoms.  They responded well to treatment and I discharged them from the hospital.  They would be rehospitalized from time to time, either on my inpatient service or another.  I would eventually see them in more detail after another 5 - 20 hospitalizations, look at the chart and notice that for some time, the diagnosis had become schizoaffective disorder.  Some would ask me about the diagnosis and some recalled the original diagnosis.  If they asked my opinion, I would always tell them what I considered to be the best answer: "As far as I am concerned, your diagnosis is still bipolar disorder.  I am basing that answer on your first hospitalization and your response to treatment.  You don't have any residual symptoms.  Having episodes of bipolar disorder for various reasons does not change the diagnosis."

One of the biases that exists about this diagnosis is that it tends to be more chronic and difficult to treat than bipolar disorder.  The reality is that bipolar disorder can be associated with a significant number of losses in terms of social network, net worth, and in some cases functional capacity.   There are frequently problems with alcohol and use of other intoxicants. Primary psychiatric disorders are always made more complicated by addictions. Like schizophrenia and depression, psychiatric research has not done a good job of defining the cognitive problems associated with bipolar disorder or coming up with successful treatment approaches. Although some rehabilitative approaches are in place for people in Assertive Community Treatment (ACT) programs, successful treatment is usually based on getting the mood symptoms in remission and the prevention of rehospitalization and suicide.  I have treated people on an outpatient basis with chronic mood disturbance and a diagnosis of schizoaffective disorder - bipolar type who work and function at an excellent level.  If they ask me what the diagnosis is - I tell them that it is probably bipolar disorder, even if they have episodic hallucinations.  I tell them "probably" because I know how the diagnosis of schizoaffective disorder is made.  And also because they are functioning well and I don't think that there is a lot of good information on the prognosis of that disorder.  At some level I am also probably biased by the idea that bipolar disorder has a better diagnosis.

My experience with the schizoaffective disorder diagnosis is a necessary backdrop for the following comments from the screenwriter Oren Moverman on whether composer Brian Wilson has a mental disorder:  "Yes, and it's public knowledge. It's called schizoaffective disorder, and it's really a combination of some schizophrenia symptoms, like hallucinations, and mood disorder, such as depression." (see transcript for reference 1).  Moverman is the screenwriter for the Brian Wilson biopic Love and Mercy.  For younger people reading this, Brian Wilson is the founder and composer for the rock and roll group The Beach Boys.  When I was in middle school in the 1960s, people of my generation started dancing to this group.  Their early genre was known as surfing music, based on that culture in southern California.  In these interviews Wilson talks about how he got started writing surfing music.   During the broadcast one of the early songs was Catch a Wave and that immediately brought me back to this time:





The Beach Boys were very successful in that type of music and made a significant comeback in the 1970s and 1980s with different types of music.  Behind all of that was Brian Wilson, a widely acknowledged musical genius who also performed live with the group in its early days.  Wilson is also known for his mental illness and substance use problems as well as his involvement with a highly controversial therapist.  The therapy methods included exerting total control over Wilson, by living with him 24/7 and having him under constant supervision by several case managers.  Wikipedia states that the cost of these services was about $20,000/month.  There was an initial 14 month episode of involvement followed by dismissal due to a dispute over fees and then another episode of involvement prior to permanent dismissal and placement of a restraining order.  Although that therapist seems to be credited in many ways with saving Wilson's life and getting him back to composing music, he was also reported to his California psychology licensing board for violations of professional conduct and according to Wikipedia resulted in a loss of license.  That same source points out that Wilson developed tardive dyskinesia and impaired functional capacity from prescriptions from this therapist's "staff".  I did not see any reference to prescribing psychiatrists or physicians.

This brings me to the inspiration for this post.  Once again it is Fresh Air's longtime interviewer for this program - Terry Gross.  In this series of interviews, Gross starts out with a story about the release of a new film about the life of Brian Wilson titled Love and Mercy.  She has two interviews that she conducted with Wilson from the past and a current interview with the screenwriter of the current film. One of the full length interviews is available on the Fresh Air web site from 2002, but I could not find the one from the 1990s.  There are also excerpts of earlier interviews played in the current interview.  The author starts out describing the focus on three discrete periods in Wilson's life and how that proved to be too much and how the focus had to be narrowed to two periods in the 1960s and 1980s.  Because of those time frames, Wilson is played by two different actors Paul Dano in the 1960s and John Cusack in the 1980s.  Moverman comments on the technical aspects of the film, like the reason for focusing on the musicians.  He also comments on the therapy controversy and states that Wilson was misdiagnosed and overmedicated.  At that point Terry Gross comments that the California Board of Medical Quality Assurance was investigating the therapist because medications were being prescribed and he was not licensed to prescribe them.

One of the most interesting aspects of Gross's work is the historical context.  She has commentary from Brian Wilson in an earlier interview commenting on the therapist controversy:

WILSON: "He's been performing a health operation on my head. He's done something that's impossible that nobody could do."

GROSS: "What do you think he's done that's really worked for you?"

WILSON: "Well, what he's done that worked for me was he's taken my body and transformed not only my physical shape, but he's transformed the chemistry within my blood, you know, from dirty to clean. And when you go through those transformation periods, you go through a little hell, you know what I mean? It's a little bit of hell to have to come through all that, all right?......."

Moverman thought that Wilson was referring to getting him off of intoxicants when he refers to blood chemistry.  Listen or read the complete transcript but in this section Wilson emphasizes the need for moving ahead rather than focusing on revenge for something that happened in the past.  I encourage anyone interested in this particular story or recovery from mental illness to listen to Brian Wilson's spoken words in these interviews with Terry Gross. 

Any acute care psychiatrist will probably be interested in this story.  For me it highlighted a number of issues.  Whenever I see a story like this, the usual way it is handled in the media is to get an expert and try to make diagnosis.  This is exactly the wrong thing to do at many levels.  One of the main concerns is the interplay between substance use and psychosis and mood symptoms.  In my experience, 95% of people seen in acute care and addiction settings are misdiagnosed with bipolar disorder, schizophrenia, depression, and even attention deficit hyperactivity disorder when they have a clear substance use problem that is responsible for those symptoms.  That does not mean that medical treatment is not necessary, but it probably means that it will be temporary.  I am not prepared to say that was an issue in this case, only that when you have seen that problem as often as I have that is one way to approach the issue.  The other dimension here is how difficult it is to effect changes and help people get back on path when they are clearly engaged in high risk and what is described in these transcripts as destructive behavior.  There are really very few options left for people with problems as severe as the ones that Brian Wilson was going through.  In most cases, it is a number of emergency department visits and brief admissions to psychiatric units.  I can say without a doubt that problems this severe are not reversible by those interventions or outpatient visits for twenty minutes to see a psychiatrist every one to three months or seeing a therapist every week for an hour.  Most people stop seeing the therapist after a visit or two.  They may have the thought that they are seeing the therapist because it is somebody else's idea.  

I certainly do not condone the therapy methods used Wilson's case, but fully acknowledge that our current systems of care are not likely to produce a positive result for persons with severe disabilities.  Above everything else this is a story of recovery.  Brian Wilson endured acute symptoms and significant disability and came out the other side.  He continues to write and produce music and that music inspires millions of people.  


George Dawson, MD, DFAPA


References:

1:  Fresh Air with Terry Gross.  'Love & Mercy' Brings The Life Of Brian Wilson To The Big Screen'.  June 18, 2015.

2:  Fresh Air with Terry Gross.  Producer And Arranger Brian Wilson, A Genius Of Rock.  August 27, 2002.

Supplementary:

I have not seen Love and Mercy yet but will probably add a few comments here when I have.

Attribution:

By Brocken Inaglory (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons