ADHD - 28 Discussion Points

 

There was some of the usual controversy in the media today.  Is Attention Deficit~Hyperactivity Disorder over diagnosed or underdiagnosed?  The usual controversy contained the usual stories of how easy it is to get a diagnosis of ADHD in some places.  In some places it seems like just a matter of expense - a thousand dollar test battery. In other places there are people disabled by the condition who cannot get adequate treatment.  In the meantime there are international experts cranking out reams of papers on the importance of diagnosing and treating this condition in childhood. Occasionally an article shows up in the papiers about the cardiovascular safety of these medications. And in the New England Journal of Medicine there was a paper about a higher incidence of psychosis due to these medications.  Where does the reality lie?

I was fortunate enough to have worked at a substance use treatment center for about 12 years just prior to retiring. Only adults were treated at that facility. A significant number of them were diagnosed and treated as children. There were also a significant number of patients newly diagnosed as adults - some as old adults in their 60s and 70s. Whether or not ADHD can occur as a new diagnosis during adulthood is controversial and establishing a history consistent with childhood ADHD is problematic due to recall errors and biases. Secondary causes of ADHD in adults such as substance use problems and brain injuries increases in prevalence.  Although I am speculating, secondary causes seem a more likely cause of attentional symptoms in adults and therefore acquired ADHD without childhood ADHD if it does exist is an entirely different problem.

Prescribing stimulants to patients who may have stimulant use disorders is problematic for a number of reasons. Initially we had an administrative safeguard on the practice. Stimulant prescriptions could only be approved with a second opinion by another psychiatrist after reviewing the record. Eventually we had a core of psychiatrists who practiced the same way and the second opinion was no longer necessary.  Over the course of 12 years I developed these discussion points.  I think they are a good example of the minimum ground you need to cover in an evaluation for ADHD.  I typically had a 60-90 minute time frame to work with and could see people on a weekly basis for 30 minute follow ups. These evaluations were often controversial and resulted in collateral contacts, typically with a family member who was advocating for the stimulant prescription. 

A few basic points about ADHD and establishing the diagnosis. Like many psychiatric disorders there is no gold standard test.  Like some of the media discussions, I have been told that a person underwent days of testing before they were given the diagnosis of ADHD.  These are typical paper and pencil tests, but there have also been tests based on watching a computer screen and even crude EEG recordings. There are a few places that use very sophisticated brain imaging techniques. Unfortunately none of these methods can predict a clear diagnosis or safe and effective use of a medication that can reinforce its own use.  That leaves clinicians with diagnostic criteria and and a cut off based on functional status as a result of those symptoms.  That may not sound like much, but it eliminates a large pool of prospective ADHD patients who have no degree of impairment and those who are obviously interested in possible performance enhancement rather than ADHD treatment.  

Stimulant medications are highly abusable, as evidenced by several epidemics of use dating as far back as 1929. We are in the midst of a current epidemic.  For those reasons it is important not to add to the problem as either the individual or population levels. In my particular case, I was seeing patients who were all carefully screening for substance use and adequate toxicological screening. Since they voluntarily admitted themselves into a treatment center it was also more likely that they recognized the severity of the problem and were more open to treatment.  Even against that background - it is worth covering the above points.  Covering those points often involves repetition because of cognitive problems in detox or disagreement.

These are just a few health and safety considerations. My main concern in this area is that psychiatric treatments somehow have the reputation that they don't require medical attention. They are somehow isolated from the rest of the body. The person prescribing this medication needs to assess the total health status of the individual and determine if the medication prescribed is safe to use. Cardiac and neurological conditions are at the top of that list. I gave a blood pressure example because I have been impressed with how many people tell me that their blood pressure was not checked after a stimulant prescription or a stimulant was started despite diagnoses of uncontrolled hypertension, cardiovascular disease, cardiac arrhythmias or cerebrovascular disease.  These were typically new prescriptions in older adults with no prior history of ADHD.  

Coexisting psychiatric disorders are also problematic. Most have associated cognitive symptoms if they are inadequately treated. That is not a reason to diagnose ADHD or start a stimulant medication.  Typical symptoms that can be caused by stimulants are have to be recognized and the medication must be stopped if adjusting the dose is not helpful.

It is important to keep the range of biological heterogeneity in mind. Once you have narrowed down a population of people who most likely have ADHD, they will not all have a uniform response to medication.  They may not all want to take medication.  As adults many stopped taking ADHD medication and adapted to a work and lifestyle that works very well for them. That is a very suitable outcome for an initial assessment.  There is another group who want to try a verbal therapy for ADHD in some cases because they recognize they can no longer take stimulants because they were escalating the dose. That is also a suitable outcome for the assessment. In those people who have ADHD are want to take a medication, I think a non-stimulant medication like atomoxetine is a good place to start. In my experience it works very well.  Disagreement about stimulants, especially in people with a stimulant use disorder typically requires extended conversations with the patient and their family. A quality control initiative can provide very useful data for that conversation. I suggest that any clinic or clinician who prescribes stimulants collect outcome data on those prescriptions.  The key piece of data is a comparison of the relapse rate of those patients taking stimulants compared with patients treated with non-stimulants. Other data could be collected as well - like how long the prescriptions were refilled. There are rules about collecting that data depending on your practice setting.  Check those rules first.  Outcome data will be the best data on whether a correct decision was made about prescribing the stimulant.

I added the following slide based on polypharmacy considerations in the paper cited in reference 1.  This is a common clinical problem that needs to be approached rationally and that includes limit setting on the concept that every side effect or symptom needs to be addressed by a medication rather than a medication discontinuation, reduction, or substitution.  I always include a discussion of rare but serious side effects, synergistic side effects, drug interactions, interactions with comorbid medical problems and associated medications, and very serious interactions that could lead to hospitalization or death, like serotonin syndrome. 

I am going to end on a note about countertransference based on a disagreement I had at a conference about my methods. The speaker advocated for prescribing stimulants as a general operating practice for anyone with ADHD. When I confronted him about the problem of substance use he claimed his motivation was that he considered it his priority to "help" people and he thought that stimulants were the most helpful medication.

Whether or not a medication is helpful for any psychiatric disorder depends on a very careful assessment and clinical expertise that considers several dimensions including the potential risks and benefits for the patient and the incorporation of the patient preferences and values into the clinical decision making process.  In my evaluations, I try to sum all of that up in an informed consent discussion. In the area of ADHD evaluation and treatment, that covers a lot of ground and there is no simple uniform recommendation.

George Dawson, MD, DFAPA

Photo Credit:  Many thanks to my colleague Eduardo A. Colon, MD for allowing me to use his photos. 

The Beginnings Of True Pharmacosurveillance

From:  Morbidity and Mortality Weekly Report (MMWR)  October 16, 2015/ 64 (9): 1-14.

I am an advocate of real pharmacosurveillance of anyone prescribing medications in the United States.  To some that might seem like a controversial statement and it needs to be argued at a couple of levels.  There will be some privacy advocates who suggest that medication information is protected information.  Sensitive medical information can be extrapolated from prescriptions and all medical diagnoses are not seen as equal in the eyes of employers or average citizens.  In this era, the knowledge that a person has a significant amount of specific medication in their possession may also put them at risk for theft or exploitation.  There are very good reasons for making sure that this information is not leaked to the general public.  The overriding argument is public safety defined as making sure that a person seeking medical help is going to see competent physicians or in this era competent prescribers.  There are many reasons why a prescriber may not be competent and may put patients at risk, but one of the most significant reasons is that they have developed a practice or prescribing that makes them an outlier.  They are prescribing medications or combinations of medications in a manner that is not like the majority of practitioners. That prescribing pattern may be frivolous or unsafe.  In the case of unsafe patterns, the practitioner should receive immediate feedback and where necessary intervention.

Some reviews currently happen at some level in the US.  In hospitals and care systems where there is routine review of physicians, some cases are reviewed prescribing patterns are observed and they are given feedback.  That process is limited by a lack of standardization and objectivity.  Just a few cases may be reviewed when today's information technology (IT) capability allow for reviewing all of a physician's caseload all of the time.  The review is often part of a larger process like an annual review where there may be conflicting agendas like spinning the review to make the person look as good or as bad an an administrator wants them to look.  Physicians can also be contacted by managed care organization (MCOs) or pharmaceutical benefit managers (PBMs) with letters expressing various concerns.  Examples might be patients who have filled only one prescription for antidepressants, patients seeing multiple prescribers, and polypharmacy.  These letters are often poorly thought out, probably don't apply to the physician or patient at the time the letter is sent, and seem to be heavier on public relations than the technical details of prescribing medications.  In some cases these reviews can be totally inappropriate.  To cite an example, a reviewer notifies nursing staff that a patient on lithium needs follow up and immediate blood tests upon discharge because the inpatient physician has not ordered the appropriate tests when they do not have the most recent records, have not spoken to that physician, and don't know that all of the testing has been done.

Another very relevant question for pharmacosurveillance is: "Who owns the data?"  Any managed care company that I am aware of treats patient data as their own proprietary data whether they know what to do with it or not.  I gave the previous example on this blog of asking a managed care executive for permission to use deidentified brain images for teaching purposes and being told: "Why would we want you to use our data?" despite the defined teaching purpose of the institution and a long history in medicine of teaching all of the available abnormal findings for the purpose of developing better diagnosticians.  Prescription and pharmacy data has an even more clandestine history.  Most physicians were not aware until very recently that all of their prescription data was collected from pharmacies everywhere by a company called IMS America and that information was used primarily by pharmaceutical company sales forces to monitor the products being prescribed and whether their detailing people were having an impact on those prescriptions.  The individual physician was not able to see these records or look at the trends in their prescribing data over time.  The data collection was centralized only for the purpose of selling the collected data to pharmaceutical companies or (for the past 15 years or so) buried in clinic or hospital electronic health records.  The best a physician could do would be to request prescribing data on a particular patient from their pharmacy.  That might result in 20 or 30 faxed pages of lines and lines of prescriptions, usually encompassing only the most recent years.

The state may not only claim the data, but set in place mandatory rules about how practitioners collect the data and transmit it to them.  In the state of Minnesota, all practitioners treating depression are mandated to have their patient complete PHQ-9 rating scales for depression and have those results sent to the state.  The state also monitors prescribing data on stimulant prescriptions for children and mandates that any person taking an antipsychotic medication needs to sign a written consent form.   Currently 49 of 50 states participate in Prescription Drug Monitoring Programs (PDMPs) to track drugs classified on the Controlled Substances Act Schedules II - IV.  The PDMP programs were originally set up to help law enforcement identify illegal activities with controlled substances but developed into a resource for physicians who wanted to know if their patient was getting multiple prescriptions or prescriptions that increased the risk of medications that they might be prescribing.  These pre-existing systems led the CDC and the FDA to develop the Prescription Behavior Surveillance System (PBSS) to look at the trends in the prescriptions of controlled substances.   Typically all pharmacies within a state submit data on controlled substances within a week of the prescription being filled.  The PBSS categorizes all of the data into three categories: benzodiazepines, stimulants, and opioid analgesics.  Buprenorphine is classified in the opioid analgesic category even though the primary use is for treating opioid dependent patients.  Tramadol was not included in the database until it was reclassified in 2014.  There is also a miscellaneous category that includes zolpidem and carisoprodol.  I think it probably makes sense to include GABA enhancing sedative hypnotics like zolpidem, zaleplon, and eszopiclone in the benzodiazepine category.

The preliminary data from the PBSS system that was just released in October is very interesting.  In terms of a representative sample, the eight states reported cover 1/4 of the US population and represent all 4 US Census Bureau Regions.  Prescription rates were calculated as the prescription rate per 1,000 residents as given by the most recent Census data.  Perhaps most surprising is that the rate of opioid prescribing approaches nearly one prescription for every state resident in some states in some states and the rate of opioid prescribing is twice as high as the rate of benzodiazepine or stimulant prescribing.  There are two to four fold differences in state-to-state prescribing of controlled substances across the board.   The top 1% of opioid prescribers in Delaware wrote for one out of four opioid prescriptions in the state.   The top decile of prescribers account for 50-60% of opioid prescribing but that decile does not solely account for state-to-state differences.  Specialists in pain clinics (pain medicine, surgery, physical medicine) were more likely to write more prescriptions per day but are thought to account for < 20% of all opioid prescriptions per day.   The authors suggest that most of the prescriptions in that category are written by general practitioners, family medicine, internal medicine, and midlevel practitioners.

Overlapping prescriptions ( benzodiazepines and opioids and long-acting and short acting opioids) were common.  Multiple provider episodes or MPEs defined as a resident filling a controlled substance prescription from 5 or more prescribers at 5  or more pharmacies in any 6 month period varied significantly by state, age, and the number of controlled substance schedules added.  The totals ranged from a low of 4.4/100,000 residents in Louisiana to 66.8/100,000 in Ohio.  An overall first impression of this system is that there are limitation but it clearly provides valuable information on prescribing behavior relevant to controlled substances.

The current epidemic of accidental overdose deaths was the driving force for the PBSS system.  It shows that a pharmacosurveillance system is possible, but that there are some limitations.  Data quality as inputted from the pharmacies needs to have quality control measures to assure consistency.  An ideal system would also include a diagnosis or indication.  Physician speciality would also be a useful marker.  I think that the best use of a system like this would be to allow physicians to mine their own prescription data and see how they compare with other physicians in general and within their own speciality.  Specific strategies could be developed for self correction at the earliest possible stages.  I wrote about a pharmacosurveillance system used in Wales in a previous post.  The top 5 drugs causing complications in that system were opioids, antibiotics, warfarin, heparin, and insulin - in that order.  With a sophisticated system it would be possible to pick up significant adverse drug events and monitor those events as well.    

All of the talk about patient safety these days is really about patient safety being practiced in the silos: health care businesses, hospitals, and clinics.  Places where individual health care data is considered proprietary - at least until there is a complication big enough that the state authorities mandate that it be reported for investigation.  These businesses have an inherent conflict of interest in reporting adverse drugs events and severe complications.  Pharmacosurveillance should be out there across the entire health care landscape.  It should not depend on reports about complications made by businesses that are in effect protected by patient privacy.  Complications can be actively sought out and investigated any time a prescription suddenly stops or changes.  This data also needs to be freely available to physicians so that they can look at their prescribing data relative to their peers and make changes where necessary.

It is time to view the process as as a way to learn about how to provide the safest possible environment for patient care,  rather than a way to "catch" somebody when something goes wrong.        


George Dawson, MD, DFAPA


References:

1:  Paulozzi LJ, Mack, KA, Hockenberry JM.  Vital Signs: Variation Among States in Prescribing of Opioid Pain Relievers and Benzodiazepines — United States.   Morbidity and Mortality Weekly Report (MMWR) July 4, 2014 / 63(26): 563-568.

2: Paulozzi LJ, Strickler GK, Kreiner PW, Koris CM.  Controlled Substance Prescribing Patterns — Prescription Behavior Surveillance System, Eight States, 2013. Morbidity and Mortality Weekly Report (MMWR)  October 16, 2015/ 64 (9): 1-14.

From Morbidity and Mortality Weekly Report (MMWR) October 16, 2015/ 64 (9): 1-14.

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.

Why The Binge Eating Disorder Banner Ad Is Good Marketing

I noticed a new banner ad for Binge Eating Disorder in my Yahoo pages last night for the first time.  It is one of those sophisticated ads that becomes a video clip when you click on it.  The main message of the video clip is that "Binge Eating Disorder is a real medical disorder" and it provides a link to the web site bingeeatingdisorder.com.  If you go to that site and click on the health care professionals link, you are taken to what is essentially a massive infographic on binge eating disorder with descriptions of  what is known about the epidemiology and theory of B.E.D.  There is no mention of treatment or the specific FDA approved medication from this pharmaceutical company that has been approved for B.E.D.  My speculation is that is coming once the advertisers analyze their web traffic and see how well the ad campaign is accepted.  Specifically will there be the usual outcry that pharmaceutical companies are making up diagnoses in order to sell drugs and of course the evil psychiatrists that are involved.  If a lot of that blowback occurs it would be easy to cancel the campaign, take down the web site and either come up with another campaign or go with more traditional advertising to a much less politically adept audience, namely physicians through medical journals.  I admit, the brain graphic with a slice of pizza replacing the parietal lobe is eye catching.      

This ad allows me to make a couple of points.  The first is the reason that we have epidemics of addictive drugs.  The general process is an increase in availability and exposing more people to the drug.  We do not know the genotypes at risk but in general a significant part of the population will have euphorigenic responses to addictive drugs.  Wider availability generally equates to larger numbers of users and people at risk for addiction.  An example I like to use is growing up in northern Wisconsin.  Back in the 1970s, even though it was the hippie generation, the main exposure in remote areas was alcohol and marijuana.  Flash forward 40 years and now there is widespread availability of practically all drugs of abuse in rural areas, including intravenous heroin.  Anytime an addictive drug comes into the marketplace there is a risk that level of availability will lead to more addiction and complications of addiction.  In the case of the first amphetamine epidemic, it was marketing and general use for a number of disorders that did not respond to the medication and marketing products like benzedrine inhalers that could be easily abused.  In the end there were thousands of amphetamine containing products until all of them were moved to Schedule II and under much tighter regulation.

The second point is that the FDA clearly does an inadequate job of preventing addiction and complications of addiction.  There should be no doubt that the main objective of the FDA is to get pharmaceuticals out into the marketplace as soon as possible.  Although politicians like to grandstand on the idea that the FDA prevents the release of life-saving drugs or builds regulatory hurdles that lead to unnecessary expense there appears to be less and less evidence that is true.  Those same politicians seem to favor quicker release and less regulation.  It is fairly clear that the FDA has minimal scientific requirements.  The release of multiple new opioids during the time of an opioid epidemic of overdose deaths and against the recommendations of the Scientific Committee would be a case in point.  A further case in point is that none of these new opioid drugs is a unique compound.  They are all basically mixes and matches of old compounds in patentable dose sizes and various possibly tamper proof formulations.   Even as I type this note I am being informed that the FDA has accepted an application for reviewing a new drug that is a combination of extended release oxycodone and naltrexone.

The FDA clearly has a lax approach to potentially addictive compounds and they cannot depend on post marketing surveillance or their so-called REMS (Risk Evaluation and Mitigation Strategies).  A reasonable approach would be to use a gatekeeper strategy and monitor those physicians for complications from prescribing controlled substances.  Since agencies and regulators at all levels seem to believe that they can teach all physicians to prescribe controlled substances with an equal low level of skill, the time of the gatekeeper option is in the past.  The main FDA approach is post marketing surveillance or basically waiting to see what happens.  In the case of addictive drugs this is even a worse idea than with other risky medications.  The post marketing surveillance depends on reports from physicians, patients or other health care professionals.  Reporting a complication from a controlled substance is much less likely to happen for a number of reasons.  Physicians working in the addiction field may be working in settings where there is a higher standard for confidentiality than typical medical records.  Any time there is the potential interpretation of diversion or inappropriate prescribing reporting is less likely.  For these reasons post marketing surveillance is not a good approach to monitor a new pharmaceutical to see if it is being overprescribed and abused.

What is a good approach?  For decades there have been large databases that compile the prescriptions of all physician in the US.  This data was typically sold to pharmaceutical companies to gauge the success of their marketing efforts by the number of prescriptions written.  It is time that the FDA ran a database and looked at real numbers and trends in prescribing.  They would have first hand knowledge of how many new Vyvanse prescriptions were written for binge-eating disorders and where any potential prescription mills were located.  They could intervene before there was a years long or decades long problem.        

I conclude the Binge-Eating Ad is good advertising.  Someone once said that an addictive drug sells itself.  I think that is true in terms of the place that stimulants have in the collective consciousness of Americans.  They are seen as magical performance enhancing drugs that are good for whatever ails you.  I can see the pressure building in primary care clinics for Vyvanse prescriptions for Binge-Eating Disorder and patients expressing their severe disappointment if they hear their clinic will not prescribe it.  They will not understand that good advertising is not necessarily good medicine.

Creating demand for a medication with definite addictive potential seldom is.


George Dawson, MD, DFAPA

How Do So Many People End Up on Stimulants?

There is no question that thousands if not millions of people end up taking stimulants unnecessarily these days.  Addiction psychiatrists,  have a unique perspective on this that I thinks goes beyond a typical approach to the problem.  I like to consider it to be grounded in behavioral pharmacology and neuroscience.   For the sake of this essay I will limit my remarks to all adults who are college aged or older and should not be taking stimulants.  Neuroscientific discoveries in the area of brain maturation suggest that a significant portion of the college-aged individuals might not make the same decisions they make a decade later, but the practical consideration is that there are millions of people in college making decisions about stimulants every day.  There are several ways to look at the problem.  The best approach I can think of is to look at the various ways that patients present for treatment.  The request for stimulant treatment can be subtle or overt.  Unlike some the papers in the current literature, I don't think that the diagnostic questions here are subtle.  During an initial clinical assessment - diagnosis and treatment commonly overlap and in some cases that I will illustrate treatment considerations become primary in the initial minutes of the interview.

The general psychiatric interview has always been a screen of sorts.  My recollection is that it was typically more problem focused in the past.  Over time, that interview started to incorporate more disorders as a focus of inquiry.  On the outpatient side the disorders added been primarily Post Traumatic Stress Disorder and Attention Deficit-Hyperactivity Disorder in non-geriatric populations.  Any time a screening is being done whether it uses a symptoms checklist or a lengthy interview there is always the chance of missing the true diagnosis or adding a diagnosis that is probably not there.  Here are a few examples.

1.  "I have been depressed for the past ten years...."  An inquiry about mood disorders at some point will focus on concentration.   Impaired concentration and attention span occurs in a number of psychiatric disorders.  Combined with some developmental history and a history of chronicity it is easy to see the problem as a missed diagnosis of ADHD and initiate treatment for that disorder in addition to the primary mood disorder.  There are problems with that approach especially when the history of the mood disorder is clear and it has never been adequately treated.

2.  "I have a diagnosis of bipolar disorder - manic and these medications aren't working...."  ADHD in adults rarely presents as hyperactivity so severe that it could be mistaken for mania.  Manic episodes are also phasic disturbances making it very unlikely that there would be many patients in any single practice who were both manic and had ADHD.  In the cases where it does happen stimulant treatment complicates the treatment of bipolar disorder and can lead to worsening mania, delusional thinking and hallucinations.

3.  "My son/daughter has ADHD....."  There are two variations in this interaction.  In the first, the parent is told about the high heritability of ADHD and advised that they also probably have it and can be assessed for it or mention to their primary care physician that they may need treatment for it.  In the second, the parent of a child with an ADHD diagnosis reads the diagnostic materials and comes into an appointment and says: "You know, I have read the symptoms and think that I have them.  Should I be treated for ADHD?"

4.  "I have always had a problem reading and I was  never any good in school..."  A common approach is to view this as ADHD, do the screening and proceed with treatment.  Physicians in general have had very little training in the assessment or treatment of learning disorder and although there is comorbid ADHD and learning disorders there is also a significant population of people with pure learning disorders who do not have ADHD.

5.  "I took my friend's Adderall and felt like I could concentrate and study for the first time in my life.  I did a lot better on that test...."  The population-wide bias is that stimulants are a specific treatment for ADHD rather than a drug that will temporarily improve anyone's energy level and attention span.  There is also the cultural phenomenon of cognitive enhancement or using stimulants as performance enhancing drugs that may be driving this request.  It is known that the availability of stimulants on campuses and in professional schools is widespread.  This is associated with students selling their prescriptions for profit and availability of stimulants illegally obtained for the purpose of cognitive enhancement.  The issue is further confused by position statements in scientific journals that support this practice.  I have not seen it studied, but it would be interesting to see questions and responses about cognitive enhancement asked at student health centers and practices that see a lot of college and professional students.

6.  "I have ADHD and need a prescription refill...."  It may be true that the patient has a clear-cut documented diagnosis prior to the age of 12 (DSM-5 criteria).  But what has happened since that initial diagnosis in childhood and now is critical history.  Has there been continuous treatment since then or has the treatment been disrupted.  Common causes of disruption include stimulant side effects, symptom resolution with age,  and co-occuring substance use problems.  A detailed history of the course of treatment since childhood is needed to make the decision to continue or reinitiate treatment.

7.  "I heard you had a test for ADHD...."  This question often initiates screening at a higher level.  There are any number of places with extended neuropsychological batteries, brain  imaging tests, or EEG tests that they claim will definitively diagnose ADHD.  In fact, there are no tests with that capability.  I have heard one of the top experts in the world on ADHD make that same statement and he was also a neuropsychologist.  I have had several years of experience with quantitative EEG machines and know their limitations.   At this point several hours of extended testing adds nothing to a detailed interview, review of collateral information, and symptom checklists to basically assure that all of the questions have been asked.

8.  "My meds need to be adjusted....."  This could be a question from a person in treatment for another problem or a person already being treated for ADHD.  The unstated issue here is the underlying belief that by adjusting a medication one's mental processes will be closer to perfection.  A child psychiatrist that I work with said it best:   "The goal in treating ADHD is to get them more functional, not to perfect their functioning."  I think the unrealistic goal of perfection drives a lot of prescriptions that exceed the recommended FDA limits.  It also explains a lot of "rescue medications" superimposed on sustained release preparations like Adderall.  Anyone familiar with the pharmacokinetics of sustained release drugs should realize why rescue medications (like immediate release Adderall on top of sustained release Adderall XR) are unnecessary.

9.  "I can't stay sober if I can't get treated for ADHD....."  This can be a complicated and confusing situation.  The child psychiatry literature had suggested initially that children with treated ADHD were less likely to have substance use disorders as adults than children with untreated ADHD.  As the evidence accumulates that is less clear.  Many adult psychiatrists and some addiction psychiatrists have extrapolated those equivocal findings to mean that treating a known or new diagnosis of ADHD in an adult will improve treatment outcomes for ADHD.  There is no evidence that is true.  Some addiction psychiatrists believe that the opposite is true, that there is a cross addiction phenomenon and that treating a person with an addiction makes it more difficult to stay sober from their drug of choice.  If the person is addicted to stimulant medication and has a clear history of accelerating the dose of stimulants or using them in unorthodox ways (intravenously, smoking, snorting, etc) it is very unlikely that person will be able to take a stimulant prescription in a controlled manner.  It is also very possible that the person making this request has a long history of experiencing prescription or street drugs as being necessary to regulate mental functioning.  That can be highly reinforcing even if the effects are sustained for hours or less.

10.  "I have been sober for one month and can't focus or remember anything......" Subjective cognitive problems are frequent during initial sobriety.  The substance used and total amount used over time probably determine the extent that the cognitive changes persist, but it is a difficult problem to study for those same reasons.  Clinicians know that there are cognitive effects but there is no standard approach to the problem.  From my experience, I think that two months sober is the absolute minimum time to consider evaluating subjective cognitive problems.  Even at that time getting collateral history about the person's cognitive and functional capacity and problem solving with them on work arounds would probably be the biggest part of the treatment.

The above scenarios are not exhaustive and I probably could come up with another 5 or 10 but they are illustrative of pathways to questionable stimulant use.  The common thread here is that anyone in these scenarios can endorse all of the symptoms of ADHD.  Figuring out what those symptoms are is fairly obvious on many checklists.  One of these checklists shows the symptoms and checkboxes necessary to make the diagnosis in grayed out panels.  It is easy to fake the symptoms in an interview or on a diagnostic checklist.  It takes a lot of hard work on the part of the physician to figure out not only who might be faking but also who has the symptoms but not the diagnosis.  One of the features of the DSM that was attacked by several critics during the pre-release hysteria was the "generic diagnostic criterion requiring distress or disability" to establish disorder thresholds (DSM-5 p 21).  In the case of ADHD that is Criterion D "There is clear evidence that the symptoms interfere with or reduce the quality of social, academic, or occupational functioning."  (DSM-5 p 60).

The diagnosis of ADHD is generally not the diagnosis of a severe functional disorder.  As a psychiatrist who practiced in a hospital setting most of the people I assessed clearly met the functional criteria by the time I saw them and diagnosed severe mood disorders, psychotic disorders, substance use disorders or dementias.   Many of them were by definition unable to function outside of a hospital setting.  It is an entirely different assessment when faced with a successful professional who has worked at a high degree of competence for 20 years who presents with any one of the above problems because they think they have ADHD.  It takes more than a review of the diagnostic criteria.   It takes an exploration of the patient's motivations for treatment.  What do they hope to accomplish by treatment?

It also takes a conservative prescribing bias on the part of the prescriber.  Stimulants are potent medications that can alter a person's state of consciousness.  They are potentially addicting medications and that can result in craving or wanting to take the medication irrespective of any therapeutic effect.  The wide availability of stimulants led to the first amphetamine epidemic in the United States.   When I first started out in psychiatry, I was still seeing people who became addicted to stimulants when they were widely prescribed for weight loss.   It is well known that the medications were ineffective for weight loss but people continued to take them at high doses in spite of the fact that they had not lost any weight.  In talking with people about what drives this many people feel like they are only competent when taking stimulants.   They believe that their cognitive and functional capacities are improved despite the fact that there is minimal evidence that this is occurring from their descriptions of what they are doing at work or in their family.

There are a number of strategies in clinical practice to avoid some of the problems with excessive stimulant prescriptions that I will address in a separate post.  My main point with this post was to look at some ways that people with mild subjective cognitive concerns, addictions, people seeking cognitive enhancement, people who have been functioning well but believe that they can function better come in to treatment for ADHD and get stimulant prescriptions.


George Dawson, MD, DFAPA

Supplementary 1:  Literature was used to construct these hypothetical scenarios.

The Cure For Overprescribing

I  felt compelled to get this down because the continued wheel spinning on this subject is really starting to annoy me.  People are wringing their hands like they either don't know what to do or they angrily invoke some model that suggests a solution but not really.  The two common models invoked are the "medicalization" of society and the other is some sort of conspiracy (Big Pharma, psychiatry) to invent diagnoses and indications for prescribing medications in order for Big Pharma to make more money.  The recipients of all of the overprescribing are seen as hapless victims who never stood a chance in the face of the medicalization-conspiracy juggernaut.  All we have to do is stop the Big Pharma-monolithic psychiatry steamroller.

Some of the "solutions" to this dilemma are equally far fetched.  First of all lets say that any physicians affiliated with Big Pharma in any way need to report all of those connections.  There was recent evidence posted that this was not slowing down physician interest in these jobs - temporary or otherwise.  It is after all a free country and one where you have to make money to survive.  Physician compensation is dropping as the workload goes through the roof.  The reimbursement and hassle in psychiatry is so onerous that psychiatrists are the least likely speciality group to accept insurance.  Many physicians would like nothing better than to work for a pharmaceutical company.  So the lack of slowing down is certainly no surprise to me.  Those who are naive to the way transparency works probably thought that physicians would be too ashamed of their appearance of conflict of interest.  That is after all what we are talking about - an appearance of conflict of interest.  The prototype for transparency is the US Congress whose members blatantly take money from and provide easy access to the same industries that they regulate.  If transparency doesn't slow down Congress, why would it slow down physicians who are often in positions where they are actually being paid for rendering a service to the company and there is no evidence of  quid pro quo.

Another solution is to isolate physicians and trainees from pharmaceutical company representatives and  promotional materials.  Probably some of the weakest research in the history of the world is the research that shows that pharmaceutical promotions and advertising influences physicians to prescribe drugs.  The only weaker research is that Maintenance of Certification measures are worth the time and effort.  Not only that but by now it should be pretty clear that throwing pharmaceutical reps to the curb has not diminished the overprescribing of just about anything.  Practically all of the over prescribed antibiotics right now are generics.  The same thing is true of the overprescribed benzodiazepines and antidepressants.  As far as I can tell most of the overprescribed opioids are the usual hydrocodone/oxycodone and acetaminophen preparations and 30 mg generic oxycodone tablets.  Pharmaceutical company detailing has nothing to do with why all of these drugs are overprescribed.  Every hospital and clinic has a Pharmacy and Therapeutics Committee responsible for a formulary and they often have specific strategies to reduce costs associated with the most expensive drugs on that formulary.   I spent over a decade on two different P & T Committees.  I have never seen any member try to push through a drug - past about 20 physicians and PharmDs, based on a piece of pizza or a donut that a pharmaceutical rep gave them.  Even thinking that could happen is absurd.

What about the DSM-5 conspiracy?  What about the bereavement exclusion?  Won't that open up tens of millions of mourners to the hazards of antidepressant medications?  Only if their primary care physician is fairly clueless.  As I have previously posted psychiatrists have studied the problem and the solutions that Paula Clayton found 40 years ago are no different than today than they were then. It certainly is possible that treating rating scale results can increase antidepressant prescribing.  But that is currently considered state-of-the-art measurement based care by managed care organizations and some governments.  That is a clear force that facilitates overprescribing.

What about cognitive errors?  Do physicians really overprescribe because they lack the technical knowledge on how to prescribe?  I really doubt that is the problem.  I would cite the case of overprescribed antibiotics.  During my training and for many years after the Sanford Guide to Antimicrobial Therapy was considered definitive guidance for antibiotic therapy.  As HIV therapy increased in success and complexity an accompanying manual The Sanford Guide to HIV/AIDS Therapy came out.  Every medicine and surgery house officer and many staff counted on the microscopic type on these pages for definitive guidance on prescribing antibiotic and antiviral therapies.  It was just a question of identifying the pathogen, determining if the patient could tolerate the medication, and prescribing the drug as recommended.  So how is it possible that antibiotics are overprescribed?

So what are the real reasons for overprescribing?  The overprescribing literature extends back well over 20 years at this point.  Solutions are not readily found.  That literature generally comes down to particular class of drugs and the progress in that area.  I recently reviewed the REMS strategy to the current opioid problem and why I did not think that would work.  It really comes down to two things and neither of them has to do with a diagnosis or medicalization.  The first is that health care systems are currently set up to offer some type of test or pill as a solution to most problems.  At least when they are not claiming that they are responsible for your cradle-to-grave health and giving you a gym membership discount.  All of that goes out the window when you enter the clinic and have 5 or 10 minutes with a doctor.  In the case of mental health care, many of the conditions that present in primary care are better treated with psychotherapy than with medications, but most primary care physicians are not trained in psychotherapy.  Some are trained in motivational interviewing, but to suggest that will be successful in many of their patients is really an insult to the problems facing them.  Primary care physicians see patients with very difficult refractory problems.  These patients will see a specialist once or twice and then go back to their primary care physician for care with the same difficult problems.  Not overprescribing in many of these situations is really a question of limit setting rather than motivational interviewing.  That is especially true if the prescription is a drug that is addicting or can cause an altered state of consciousness.

The other issue is that systems of care these days, are set to run on the concept of customer satisfaction rather than excellent medical care.  The idea that a customer may not get what he or she wants is anathema to the MBAs that are currently in charge of the system.  The trickle down effect is that the physician who is setting limits on benzodiazepine, sedative hypnotics, stimulants, or opioid prescriptions will not get good customer satisfaction ratings and their compensation and role in the organization may be diminished as a result.  Health care systems that allow patients to rate their doctors on satisfaction ratings without considering that patients might be dissatisfied with reality should be held to task.

The second factor is the physician himself.  How many physicians have thought about all of the unconscious factors that lead to their overprescribing?  My guess is not many.  The problem of overprescribing is viewed as an informational deficit.  It is believed for example that teaching physicians all about chronic pain and the pharmacology of opioids will somehow reduce opioid overprescribing.  I don't see how anyone can come to that conclusion.  All physicians are taught pharmacology and most have experience prescribing opioids.  That approach seems as naive to me as the Joint Commission pain initiative in the year 2000.  Physicians need to determine for themselves why they are uncomfortable not giving a patient a prescription for whatever they are asking for.   I have heard a wide variety of reasons in my career and most of them have nothing to do with the indications for the drug.  The majority had to do with the physician believing that they could do something to alleviate the patient's distress and that wish was independent of what the diagnosis or indication for the drug was at the time.   The new variation on that theme is that physicians are somehow capable of overcoming the effects of a chronically impoverished environment, severe ongoing adversity, and either an inability or a resistance to change by prescribing a drug.  That is basically the same rationale that people use when they are addicted to drugs and alcohol.  They hope to use something to block out reality for a few hours.  Overprescribing will not change that.  The other interesting consideration is that the diagnosis is irrelevant.  It is tacked on afterwards for a prescription that is written for no real medical reason.

There needs to be better standards for determining what constitutes overprescribing and what does not.  I recently corresponded with the lead author of a paper looking at the issue overuse of health care services in the US (see reference 2).  The authors conclude that while there is ample evidence of overuse, the scope of research is limited.  Some of this is due to difficulties with definition and that would apply to the issue of overprescribing psychiatric medications.  The studies that frequently make the headlines have significant methodological problems.  A study I recently posted used two different data sources to conclude that antidepressants were being overprescribed.  The studies need to be more than prescription, survey and administrative data.  Those studies will necessarily be labor intensive and expensive.

In the end, I always come back to the informed consent model.  If the patient is competent to consent in most cases the physician and patient can have detailed conversation about the prescription including the risks and benefits and what it would like to go without it.  These are usually lengthy conversations.  These are tough decisions based on the fact that nobody wants to take medications regularly or see doctors for the purpose of continuing medications.  My own personal experience is consistent with what my patients have told me over the years - some change is desperately needed and that is often how the medication is viewed.  In that context people will often try medications with significant toxicity.  The medicines advertised on TV with death as a stated side effect are cases in point.  But no matter how much information passes, the physician needs to be the ultimate judge of whether the medication is a good idea.

It can never be a decision that is taken lightly.          

George Dawson, MD, DFAPA

1: Gordon M, Catchpole K, Baker P. Human factors perspective on the prescribing behavior of recent medical graduates: implications for educators. Adv Med Educ Pract. 2013 Jan 10;4:1-9. doi: 10.2147/AMEP.S40487. Print 2013. PubMed PMID: 23745094

2: Korenstein D, Falk R, Howell EA, Bishop T, Keyhani S. Overuse of health care services in the United States: an understudied problem. Arch Intern Med. 2012 Jan 23;172(2):171-8. doi: 10.1001/archinternmed.2011.772. Review. PubMed PMID: 22271125


Supplementary 1:  I was going to add a detailed explanation of my bubble diagram to this post but it is too long.  Look for a separate post about the bubbles.

Supplementary 2:  An updated higher resolution bubble diagram is located at this link.