The Myth of "Rescue" Medications

First off a clarification.  I am talking about the specific case where a short acting medication is added to a long acting form of the same medication and not "as needed" medication in order to determine the correct daily dosage.   In my line of work it occurs in two situations, long acting stimulants and their immediate release versions and long acting opioids and their immediate release versions.  I will illustrate that these practices are driven by myths about the medication rather than pharmacokinetics.  There is always the additional consideration about addiction lurking in the background, but the conscious and unconscious determinants of addiction frequently depend on the myths that I will be discussing about medication effects.

The example that I will use here is Concerta (long acting methylphenidate) compared with immediate release methylphenidate.  The graph from the package insert above shows the plasma concentration from a single 18 mg dose of Concerta and three successive 5 mg doses of immediate release methylphenidate.  As noted in the comparison of the curves and additional pharmacokinetic parameters the curve associated with three successive doses of immediate release methylphenidate is nearly identically replicated by a single dose of Concerta.

What is happening when additional doses of a immediate release methylphenidate are prescribed to a person who is already taking Concerta?  I  have seen this happen with sustained release stimulants and sustained release opioids.  I have seen it happen as a single dose of the immediate release preparation or multiple doses over the course of the day.  The patient is usually advised that this is a "rescue" medication that they should take if needed.  The first possibility is that the dose of sustained release medication has not been optimized and a higher dose of the sustained release medication needs to be given.  That is usually not the case.  The most frequent reason for taking the rescue medication is that the patient believes they are experiencing breakthrough symptoms and for a moment they need a higher dose of a medication.  There are serious problems with that concept.  As can be seen from the curves comparing Concerta and methylphenidate it does not make pharmacokinetic sense.  Any additional dose of immediate release methylphenidate on top of Concerta would greatly increase the expected plasma concentration at that point.

The main problem is that both ADHD and non-cancer pain are chronic conditions.  By definition they do not respond well to medications and they will not resolve typically with any amount of the medication.  Many people who take stimulants for ADHD assume that the human brain can be fine tuned with a medication.  There is also a widespread myth that they are cognitive performance enhancing drugs.  The real effects of stimulants are modest at best and there is no good research evidence to support a cognitive enhancing effect.  A similar bias exists for the use of opioids for chronic non-cancer pain.  The person believes that "If I take enough of this medication - my pain will be gone."  Study after study of opioids for chronic non-cancer pain shows that pain relief with opioids is modest at best, with results very similar to what would be expected with non-opioid medications like gabapentin and antidepressants.

There are secondary problems with believing a medication will produce perfect cognition or perfect pain relief.  The first is a tendency to see any medication with such powerful abilities as being able to solve a number of problems that are not the primary indication for the medication.  As an example, with a stimulant - if this medication has such a profound effect on my cognition maybe it can help with with other difficult problems like excessive appetite and weight problems or feeling like I don't have enough energy at certain times during the day.  With the opioid the  thought typically is that it can be used for mental pain as well as physical pain and it is used to treat anxiety, depression, and insomnia.  Whenever a medication is not used strictly for the prescribed indication there is a risk that it will be used for "what ails you."  The danger is dose escalation and addiction.  There is also the risk of attributing too much of an effect to the medication when it does not appear to be doing much.  A person may start to believe that they can't function without the medication but a detailed review of their target symptoms and ability to function shows that there has been a negligible effect.  And finally there is the danger of taking a medication that may produce euphoria, increased energy, and create a sense of well being and not realizing that at some point that is the only reason the medication is being taken.  I have had many people tell me that the medicine did nothing for their pain or cognition but that they kept getting refills because they "liked taking it."

There is what I call the Talisman effect, but probably to a lesser extent than with benzodiazepines.  Many people develop the idea that they are taking a medication that is much more effective than it really is and therefore they have to take it with them wherever they go.  They are conferring what are essentially magical properties to the medication and at some level thinking that they are unable to function in life without it.  They get anxious if they think about not having it or running out.  This not only causes a lot of unnecessary anxiety, but it also prevents the person from using other psychological or conditioning techniques that may work as well or much better than the medication.

These are some of the problems with the idea of taking a rescue medication if you are already on a long-acting form of the medicine.  Physicians in general do not do a good job of explaining these potential problems or even the basic problem of taking a medication that causes euphoria or reinforces its own use.  A more widespread recognition of these problems would go a long way toward curbing overprescription, overuse, and addiction to these medications.    

        

George Dawson, MD, DFAPA

References:

1.  Graph of plasma concentrations of Concerta and methylphenidate is from the package insert on FDA web site at:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021121s014lbl.pdf

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

Live by the Customer Satisfaction Ratings and Die By Them

My original intent was to look at the problem of what happens to a group of physicians who are sailing along with very high patient satisfaction ratings.  Then for no particular reason, their ratings drop by about 20-25%.  At the high point they did not question the validity of the ratings.  They just assumed the satisfaction ratings reflected their high quality work.  The problem is that nothing they did changed and suddenly their ratings were significantly lower and people were looking for explanations.  Hence the title of this post.  If these ratings really mean something in the first place the physicians are suddenly thrown into a lot of self doubt.  If they believe the ratings are unscientific, designed by people who don't know much about survey design or sampling, and are actually biased because of the way the staff presents the surveys - they are much less worried.

I posted to above bar graph as an introduction to this post.  It is a composite of the opinions that several primary care physicians have given me about the correlation between benzodiazepine and opiate prescriptions and customer satisfaction ratings.  More prescriptions for controlled substances equals greater customer satisfaction.    Some clinics have adapted to this by letting patients know that they do not prescribe benzodiazepines or deal with psychiatric disorders.  That eliminates physician-to-physician variability in prescribing.  It also demonstrates that certain overprescribed medications are viewed as more serious than others.  I have not for example seen any similar clinic rules for antibiotics even though they are also widely over prescribed.

I hope it is not a news flash to anyone that highly satisfied customers in the health care system have the highest mortality and probability of hospitalization (1).  I know that at least some of the customers out there may be very surprised to hear that doctors can't be rated like a Toyota dealership.  Toyota dealers after all have a product that is high in quality, uniform, and the same irrespective of those pesky human factors that we all have to deal with in human encounters.    I am referring of course to things like communication,  interpersonal skills, thinking capacity, personality traits and personality disorders.  A Toyota dealer is out to satisfy all customer needs in the very circumscribed area of personal transportation.  Even then there will be bumps in the road.  A customer may not like the way the vehicle has turned out or some of the results from the service department.  But generally Toyota dealers have a great product and most of their customers are highly satisfied.

This may be hard to believe but the MBAs that currently run medicine in the USA decided to introduce management principles into the field that were designed for the auto industry.   The details and names of those management principles is irrelevant at this time, but when they were introduced it was a big deal.  I had to listen to several hours of lectures on Six Sigma.  Feel free to read about it and let me know how it possibly applies to the practice of medicine.  After those lectures it was obvious to me that the MBAs running medicine were completely clueless about medical care.  One small piece of evidence in what is now a mountain of evidence that the business emphasis in managing hospitals and doctors is completely off the rails.   Most business concepts are introduced to groups of physicians as a manipulation.  They have to be because no rational person would buy what appears to be Dilbert style management.  It goes something like this:

"Look - we know that physicians don't like the idea that they can measured.   We know you don't like that idea, but let's face it, this is a new era.  Things aren't like they used to be.  The day of the physician running things is over.  You are all going to have to be accountable now.  Some day your reimbursement is going to be tied to these satisfaction ratings."

Administrators like to seethe a little bit when they play the authoritarian act with physicians.  They think it gives them more credibility.  They could also be playing off the collective seething in the room.  The logical questions followed:

"Well what about clinicians seeing patients with cognitive impairment or who are being treated on an involuntary basis.  What can you say about the validity of those satisfaction ratings?"

That led to some laughter, but no explanations.  Everybody would be rated and that was the end of it.  There would be no exceptions.  The irrational authoritarian business model rules.

Before anyone gets too bent out of shape about my view of the business model let me illustrate with an second example of what I mean.  Earlier this evening I consulted with a colleague from another state on an inpatient problem.  When that was over I asked her how things were going in general and she told me:  "It's really kind of tough.  The patients are never really stable, they have multiple psychiatric, substance use, and medical diagnoses and they are very hard to stabilize."  She was thinking about moving on.  She was in a meeting and an administrator said:  "This patient has been here (x number of days) what is the plan?"   She said:  "What do you mean what is the plan?  The plan is what the plan always is - stabilize the patient and discharge them."  Managed care administrators have the uncanny ability to blame the physician for any discrepancy with a pure business approach to medicine.  They apparently believe that hospital treatment and discharges are as predictable as Toyotas rolling off an assembly line.  That is as true for customer satisfaction ratings as length of stay outliers.  It give the administrators leverage against physicians, especially any physician who buys in to the idea that these are valid metrics.

Let me illustrate by considering two different physicians Doc A and Doc B.  Both are very competent psychiatrists, but for some reason Doc A consistently scores lower on customer satisfaction ratings than Doc B.   From the research in this area, it may simply mean that Doc B gives his patients more of what they want than Doc A.  My speculation is that personality is a big factor.  A simple mismatch between extroverts and introverts can fuel a lot of dissatisfaction.  The extroverts on both ends (doctor and patient) like to be engaged and they like the conversation to have no dead air.  A doctor that is too reserved may be perceived as being disinterested or not giving them enough in the interaction.  Some patients want special treatment and others just want confirmation of their perceptions of other doctors and in:  "I was not really impressed with your colleague.  What do you think of him?"  Psychiatrists generally know better, especially psychiatrists who recognize that their organization is set up to facilitate splitting and chaos.  There may be a difference between the doctors in terms of prescribing patterns in terms of my previous analysis of the overprescribing problem.  In this case Doc A may be known for no sleep medications, no benzodiazepine prescriptions, no opiate maintenance prescriptions and no high dose amphetamines for narcolepsy and no stimulant prescriptions for adult ADHD when the patient is functioning well in school or work.  Denying those groups of prescriptions will not only result in low physician satisfaction scores but threats of violence and suicide.  That is not to say that other tests or medication would not result in and extremely dissatisfied patient.  There are thousands of scenarios where the patient does not take the physicians advice in the manner with which it is intended and that is - the best possible advice to diagnosis or treat a problem at a given point in time.

I did not write this post to "prove" that being satisfied with your physician is necessarily a good thing or a bad thing.  If I wanted to approach problems like that I could probably get my own TV show.  The whole point here is that any potential patient-customer needs to know what these things mean.  You may not want to keep hearing the word but politics is the major reason.  People trying to sell their business based idea about medicine versus physicians who have no similar notions.  People trying to sell their idea that medicine is just like making widgets rather than treating people who have tremendous biological variability.  You don't want your Toyota to have tremendous mechanical variability, but for human beings biological variability is both a fact of life and a distinct advantage from an evolutionary standpoint.

And finally what about news from your physician that you don't want to hear.  Certainly there is widespread fear of a dreaded incurable diagnosis.  There is the concern of diagnoses associated with disability and loss of function.  But there is also straightforward advice on how to avoid fatal illnesses and disability.  The way that is presented varies considerably from physician to physician.  You have to ask yourself: "Would I rather hear that I am overweight and need to lose weight or that I should stop smoking or that I should stop using hydrocodone or alprazolam or would I rather be talking with a physician who would keep quiet on those issues?"

I don't think there is a good study of the issue and if somebody knows one please let me know so that I can post it here.  I can provide another anecdote.  I worked with a group of women once many of who consulted a female internist who was bright, attractive and wore very high fashion clothing (their characterization not mine).  Things were generally going along pretty well until this internist told some of them that they were overweight and needed to lose weight.  That elicited a very strong reaction and it seemed amplified by their perception of this physician as being "perfect".  When I thought about my experience with physicians - nobody has ever told me to lose weight even in situations where they should have.  I suggested it to a physician once and he said: "I concur with your recommendation doctor" but never told me that outright.  Social and cultural factors all play a part in the patients perception of the physician and their satisfaction ratings.

It is a good idea to keep all of those factors in mind in attempting to interpret physician satisfaction ratings especially since most consumer web sites focus entirely on these measures.


George Dawson, MD, DFAPA

1:  Fenton JJ, Jerant AF, Bertakis KD, Franks P. The Cost of Satisfaction: A National Study of Patient Satisfaction, Health Care Utilization, Expenditures, and Mortality. Arch Intern Med. 2012;172(5):405-411. doi:10.1001/archinternmed.2011.1662

From the reference:

"Patient requests have also been shown to have a powerful influence on physician prescribing behavior, and our findings suggest that patient satisfaction may be particularly strongly linked with prescription drug expenditures." (p. 408)

"While we do not believe that patient satisfaction should be disregarded, our data suggest that we do not fully understand what drives patient satisfaction as now measured or how these factors affect health care use and outcomes. Therapeutic responsibilities often require physicians to address topics that may challenge or disturb patients, including substance abuse, psychiatric comorbidity, nonadherence, and the risks of requested but discretionary tests or treatments. Relaxing patient satisfaction incentives may encourage physicians to prioritize the benefits of truthful therapeutic discourse, despite the risks of dissatisfying some patients." (p. 409)

Supplementary 1:  If you are a primary care physician I am very interested in your thoughts about how patient satisfaction scores correlate with prescriptions for benzodiazepines, opioids, and stimulant medications as qualitatively depicted in the above bar graph. 

Dangerous Medication - Part 3 - A Risk-Averse Approach To Prescribing Bupropion

Bupropion is a widely prescribed antidepressant.  It is a safe and effective medication according to the FDA.  It can be safely prescribed with a high level of success.  It is probably more widely prescribed with the advent of guidelines suggesting that it is an augmenting agent for situations where antidepressant monotherapy is ineffective.  It may also end up being used with another antidepressant if a patient is interested in using it for smoking cessation and in an off label manner for attention deficit hyperactivity disorder and to treat sexual dysfunction associated with SSRI type antidepressants.  Bupropion does have a unique position in antidepressant pharmacotherapy.  With the increased focus on electrocardiogram abnormalities, it is probably the antidepressant that  is least likely to affect the QTc interval.

Bupropion is generally well tolerated, but there are some people who develop increased anxiety, agitation and insomnia.  This people generally need to stop taking the medication or reduce the dose.  A small number of people will develop mild to moderate hypertension and depending on the situation, the medication should be discontinued or the hypertension treated.  The largest problem I see with this medication is deciding when to stop and start it based on its contraindications.  The FDA package insert (from the FDA website using the brand name) on the matter is clear:

CONTRAINDICATIONS
WELLBUTRIN is contraindicated in patients with a seizure disorder. 
 WELLBUTRIN is contraindicated in patients treated with ZYBAN® 13 (bupropion hydrochloride) Sustained-Release Tablets, or any other medications that contain bupropion because the incidence of seizure is dose dependent. 
WELLBUTRIN is also contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa because of a higher incidence of seizures noted in such patients treated with WELLBUTRIN. 
WELLBUTRIN is contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines). 
The concurrent administration of WELLBUTRIN and a monoamine oxidase (MAO) inhibitor is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with WELLBUTRIN. 
WELLBUTRIN is contraindicated in patients who have shown an allergic response to 
bupropion or the other ingredients that make up WELLBUTRIN Tablets

The package insert goes into some of the evidence for these contraindications, but the details seem fairly clear to me.  So why is it that the following happens?

1.  Patients who are not aware of the fact that bupropion can cause seizures.
2.  Patients who are prescribed this medication in spite of the contraindications.
3.  Patients with a past history or an active eating disorder taking this medication.
4.  Patients who are regularly drinking alcohol +/- sedative hypnotics taking this medication.
5.  Patients who have had generalized tonic clonic seizures taking this medication and the medicine is still prescribed.

I could go into much greater detail about some of the most extreme situations where this occurs, but I think it would be more instructive if I just cut to a few basic recommendations for the safe use of this medication:

1.  Do not prescribe it in the presence of contraindications.
2.  Do not prescribe it to anyone who has a known problem with alcohol or sedative abuse problems.  In fact, obtain a new history for those disorders at the time you are obtaining informed consent for the prescription and revisit the contraindications every time you increase the dose since the seizure risk increases with dose increases.
3.  Discontinue bupropion immediately if you are treating the patient for alcohol or sedative hypnotic withdrawal.  Have a serious conversation with that person about seizure risk an the FDA contraindications before restarting it.  People provided with that information quickly reassess the need for the medication and whether or not it has been helpful.
4. Discuss the warnings with the patient if they have medical comorbidity that is flagged in the package insert such as:

Hepatic Impairment: WELLBUTRIN should be used with extreme caution in patients with severe hepatic cirrhosis. In these patients a reduced dose and/or frequency is required, as peak bupropion, as well as AUC, levels are substantially increased and accumulation is likely to occur in such patients to a greater extent than usual. The dose should not exceed 75 mg once a day in these patients.

and:

The risk of seizure is also related to patient factors, clinical situations, and concomitant 
medications, which must be considered in selection of patients for therapy with WELLBUTRIN. 
Patient factors: Predisposing factors that may increase the risk of seizure with bupropion use include history of head trauma or prior seizure, CNS tumor, the presence of severe hepatic cirrhosis, and concomitant medications that lower seizure threshold. 
Clinical situations: Circumstances associated with an increased seizure risk include, among others, excessive use of alcohol or sedatives (including benzodiazepines); addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; and diabetes treated with oral hypoglycemics or insulin. 
Concomitant medications: Many medications (e.g., antipsychotics, antidepressants, theophylline, systemic steroids) are known to lower seizure threshold. 

5.  Seriously weigh the seizure risk of adding any medication that might lower the seizure threshold to any person who is stable on bupropion and keep that person involved of the possible seizure risk.  Do a detailed and individualized risk assessment for prescribing medications to any patients.
6.  Document the vital signs of any patient on bupropion and the trend.
7.  Do not prescribe bupropion again to anyone who has had a seizure while taking it.

I have seen bupropion prescribed in the context of all of the contraindications and warnings without seizures or other complications.  Risking a low frequency but serious complication is not the optimal way to prescribe it.  The other consideration is that the risk assessment needs to be done on an individualized basis.  A general number quoted as an average side effects from clinical trials obviously would not apply to a patient with multiple risk factors or a patient who reliably gets side effects every time he or she takes the drug.  Population based care sounds good when it is promoted by managed care companies or government agencies, but this is a good example of where that concept fails.  As I think about all of the high risk ways I have seen bupropion prescribed, I go back to the recent post on overprescriber biases and how that influences the process.  No physician trained in psychopharmacology would have these deficits on a purely cognitive level, but in the case of treatment resistant depression and a contraindication the situation may become higher risk.

That is an ideal time for consultation or referral rather than taking a chance.

If you are reading this from the patient perspective, I encourage reading the Medline Plus handout on any medication that you are taking. The FDA approved package insert is usually available on the Internet, even in the case of most generics.  I would exercise caution if you decide to study it.  In a previous post, I point out that a lot of people really don't want to know about detailed side effects in advance because they fear developing them by mere suggestion or they might avoid taking a useful medication entirely.  Some package inserts have specific "Information to the patient" that is usually designed to communicate important information.

George Dawson, MD, DFAPA

Overprescribing Bubble Diagram Explained

This post is intended to explain the bubble diagram that I used in the last post about overprescribing.  It focuses on the physician rather than a number of extraneous factors that are the speculative causes of overprescribing that do not make sense.  The literature on this is spotty.  There are a few references that include diagrams and purported mechanisms of overprescribing.  Before I consider those, I want to put down what I know.  The bubble by bubble explanation follows starting at the top left of the diagram - but each bubble is easily identifiable:

1.  Unconscious Motivations:  This is one of the areas that I consider to be the primary cause.  It encompasses both unconscious and preconscious causes.  The best way to look at it is with a few examples.  Overidentification with the patient seems to be a fairly common cause.  For example, a physician might have attention deficit hyperactivity disorder and realize that with treatment they were able to do much better academically.  They have a lower threshold for seeing the problem in others based on their experience.  In their medical group they are seeing many more ADHD patients than their colleagues and prescribing far more stimulant medications.  That is really a special case of the physician wanting to do something positive for the patient.  That can lead to a reduced awareness of other causes such as substance use or a person seeking cognitive enhancement and drive the prescription process.  The wish to be appreciated and have a positive relationship with the patient is another issue.  Consider the patient in clinic an uncomplicated upper respiratory infection.  Near the end of the clinical encounter, the patient senses that there will be no prescription and starts to get annoyed.  The patient talks about his or her past experience and how an antibiotic always seems to clear up their cold symptoms.  They put the physician on the defensive about the antibiotic issue and rather than argue with the patient - the physician hands over the prescription.  All of these scenarios and more reflect unconscious factors involved in prescribing and as far as I can tell this important area is untouched in the overprescribing literature.

2.  Medical knowledge:  This occurs at two levels.  The first is just the rote declarative knowledge that involves the memorization of factual knowledge about medications.  This seems like a fairly basic skill, but the amount of information we are talking about is encyclopedic.  To illustrate this all one has to do is to pull up recent FDA approved package inserts for drugs that are advertised on television.  All of the pharmacological details are presented in a neutral and highly detailed manner.  There is some prioritization in terms of  contraindications and precautions, but that is still a lot to memorize.  Experienced clinicians will still read these documents repeatedly and use summary references until they gain enough experience with the medication.  The second level is the patterns that become familiar when using the drug.  For example, after I have prescribed a drug enough times, I can tell anyone taking it what my experience with the medication is and what the experience of my patients has been.  That information is really not available anywhere else and it also can lead directly to additional testing.

3.  External validation:  The best objective source of external validation is prescribing medications according to the FDA approved indications and as instructed in those documents.  Off label prescriptions should be backed up by some data. I typically research all off label prescribing by doing Medline searches and looking for actual clinical trials looking at that application.  Example would include looking at the use of gabapentin for chronic pain and treatment of alcohol withdrawal.  Even though there are no FDA approved applications, there is ample evidence about how to use these medications, including very specific dosing recommendations.

4.  Conservative prescribing bias: My goal has always been to treat the primary problem but also eliminate or minimize problems related to the medication.  That is not the goal of some physicians.  I heard an expert in the treatment of anxiety disorders suggesting that patients needed to be treated to the point of toxicity with a medication and then the medication could be reduced.  That is not necessary as far as I can tell.  Another issue here is exceeding the FDA approved range for medication use.  Quality markers for dose range and multiple medications from the same class are nothing new and date back at least 20 years. This information is also part of informed consent and the patient should hear about it and other options at the time the change is being considered.  I have spent a lot of time correcting unnecessary high doses and polypharmacy, generally to the benefit of the patient involved.

5.  Social context:  A group of interested physicians who keep up on the research and analyze prescribing patterns is a robust safeguard against overprescribing. There are some settings for example where benzodiazepines or benzodiazepine related sleep medications are not prescribed in any circumstance.  Stimulant medications are used only by review with a colleague and the medical director and documentation on a signed form.  Such a review procedure is available to any group has utility in preventing variation in prescribing patterns and practice variation.  Practically every major clinic and hospital has a program that targets antibiotic overprescribing especially the overuse of expensive, toxic or antibiotics that are the last defense against bacteria with multiple drug resistance.  This social factor is a powerful safeguard against overprescribing.

6.   Physician as a source of information and teaching:   If the physician is in a position to teach patients about a medication they generally have a more nuanced knowledge about the medication.  They avoid stereotypes like: "When I see this problem I always prescribe this drug."  They are also aware of the likelihood of the patient recovering without the drug and the fact that any drug effect may be weak.  A classic example is low back pain in adults.  Patients generally lack knowledge about the importance of avoiding deconditioning and the need for ongoing physical therapy and back specific exercises.  They are generally surprised that conditioning provides a significant amount of pain relief.

These are a few brief examples about what can be done.  All of these dimensions occur in the context of political and regulatory influences.  For example, the FDA initiatives to approve potent opioid medications that are essentially not much different in terms of risk from current medications during an opioid epidemic.  Guidelines suggested by outside sources may not be very useful if there is insufficient evidence and the information is broadly disseminated to clinicians.  The bubbles listed on the diagram are potent factors in countering any trend that may lead to oversubscribing and they do not involve penalizing or threatening physicians - typical actions used by law enforcement or politicians that may have caused the problem in the first place.

The reader will note that I am not concerned about diagnostic proliferation.  I don't think that overprescribers do this based on the availability of new diagnoses.  I base this on my observations of the patterns that exist independently of new diagnoses and can provide a number of examples.  Physicians are trained to "do" something medical or surgical and over the course of my career that bias has not panned out in a number of areas.  Targeting that tendency will be more productive than complaining about pharmaceutical companies, diagnostic manuals, or guidelines especially when our major regulatory agency has the bias to get a drug out there for general use based on highly variable scientific evidence.  As recently noted the FDA can also ignore the recommendations of their own scientific committee.

In the end, the best assurance of adequate medical treatment and minimal risk from the treatment depends on the expertise and judgment of a physician.

George Dawson, MD, DFAPA  

Supplementary 1:  After staring at the diagram for a while I think I need to add a 7th Bubble that I would probably call "Heuristics".  It would focus on the cognitive and emotional biases that exist in prescribing.  For example,  everyone in their practice may have a person with an addiction who was subsequently able to take an addicting medication without relapsing to their primary addiction.  Is that a reason for making that a rule for prescribing?  There are a number of ways to look at potential biases in prescribing that can improve the evaluative structure of that process.

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.

More on Geriatric Depression and Overprescribing Antidepressants in Primary Care

A recent article in the New England Journal of Medicine adds some more epidemiological data to the issue of the treatment of geriatric depression.  The centerpiece of the article by Ramin Mojabai, MD is a graphic that is a combination of data from the National Survey on Drug Use and Health or NSDUH and the U.S. National Health and Nutrition Examination Survey or NHANES.  His central point is that the majority of people diagnosed with depression in primary care clinics do not meet diagnostic criteria for major depression.  The actual numbers for the elderly are 18% of those diagnosed with depression and 33% of those diagnosed with major depression actually have a diagnosis of major depression as assessed by rating scales or structured interviews.  The bar graphs in the A panel illustrate that most people over the age of 35 who are taking antidepressants do not meet criteria for major depression.  The opposite is true for the 18-34 year olds where antidepressant prescriptions are less than the prevalence of depression.  Panel B illustrates that the prevalence of people who were told by their clinician that they had depression and did or did not meet criteria for major depression.  In all cases the clinicians involved estimated non-major depression as being more prevalent than major depression.  Can we learn anything from these graphs?

The striking feature in Panel A is the dissociation of the total number of people taking antidepressants from the people with a diagnosis of major depression.  I can see that happening for a couple of reasons.  I would expect the number of people who are stable on antidepressant therapy to accumulate over time.  Most of them would have major depression in stable remission and would no longer meet the criteria.  A related issue is the atypical presentations of depression with increasing age.  I have seen many cases of depression presenting as pseudodementia, Parkinson's syndrome, and polyarthritis or a similar chronic pain syndrome.  In all cases, the symptoms responded to antidepressant medication but they would not meet criteria for major depression and most often the evaluation would resemble an evaluation for a medical problem.  There is also the problem of depression in the aging population who have a form of dementia.  At the upper end of this age distribution that may involve as many as 5% of the 65 year old population and they are likely overrepresented in primary care settings.  Lastly there is the problem of suicide in the elderly.  I reviewed a recent paper in the American Journal of Geriatric psychiatry that documented a decreased risk for suicide in elderly men and women who were taking antidepressants and the increased suicide risk in that group.  It is likely that many primary care physicians are concerned about that higher level of risk and this may influence prescribing for this group.  The other interesting comparison is that using different methodologies the ballpark antidepressant use in the elderly in Denmark approximates the antidepressant use on the US.  It is probably a few percentage points lower, but the study in Denmark used a more robust marker of antidepressant use (refilling the actual prescription) rather than survey questions.

The author addresses the issue of antidepressants being used for other applications like headaches and chronic pain chronic pain and states from an epidemiological perspective that two thirds of the prescriptions are for "clinician diagnosed mood disorder."  The standard used in this study of DSM major depression criteria is too strict to use as a marker for antidepressant use since there are other valid psychiatric indications that primary care physicians are aware of and treat.  Panic disorder, generalized anxiety disorder, social anxiety disorder and dysthymia are a few.  There are also more fluid states like adjustment disorders that seem to merit treatment based on severity, duration, or in many cases by the fact that there are no other available treatment modalities.  These are all possible explanation for the author's observation that the majority of people diagnosed with depression in primary care clinics do not meet criteria for major depression.

Diagnostic complexity is another issue in primary care settings.  Patients are often less severely depressed, have significant anxiety, may have an undisclosed problem with drugs or alcohol, and have associated medical comorbidity.  In an  ideal situation, a diagnosis of depression is not necessarily an easy diagnosis to make.  It takes the full cooperation of a patient who is a fairly accurate historian with regard to symptom onset and dates.  They are harder to find than the literature suggests.  The epidemiological literature often depends on lay interviewers using structured interviews like the DIS or SADS to make longitudinal diagnoses.  This approach will not work for a large number of patients and a significant number will not be able to recall events, dates, medications or prior treatments with any degree of accuracy.  With that level of uncertainty, antidepressant prescription often comes down to a therapeutic trial so that the patient and physician can directly observe what happens between them as the only available reliable data.

The  author notes that the primary intervention for depression in primary care is the prescription of antidepressants.  He talks about the ethical concerns about exposing patients especially the elderly to antidepressant drugs if it is not warranted, but he is using the major depression diagnosis here as the standard for treatment.  He makes the same observation that I have made here that mass screening for depression is not warranted based on the concern about false positives.  That stance is supported by the Canadian Task Force on Preventive Health Care.  The U.S. Preventive Services Task Force recommends screening "when staff assisted depression care supports."  My position is that screening, especially in medical populations is problematic not only from the false positive perspective but also because the screening checklist is often used as the diagnosis and an indication for starting antidepressant medications.  Screening checklists are also political tools that are used to manipulate physicians.  The best example I can think of is using serial PHQ-9 scores as a marker of depression treatment in primary care clinics even though it has not been validated for that application. As an extension of that application the PHQ-9 is used as a quality marker in clinics treating depression over time even though there is no valid way to analyze the resulting longitudinal data.

The author makes recommendations to limit the overuse of antidepressants and uses the stepped care approach with an example from the UK National Institute for Clinical Excellence or NICE.  These guidelines suggest support and psychoeducation for patient with subsyndromal types of depression.  A fuller assessment is triggered by very basic inquiries about mood and loss of interest.  Amazingly the PHQ-9 is brought up as an assessment tool at that point.  More monitoring and encouragement is suggested as a next step with a two week follow up to see if the symptoms remit spontaneously.  Medications are a third step for longstanding depressions or those that do not remit with low level psychosocial interventions.  An expert level of intervention is suggested for patient with psychosis, high risk of suicide, or treatment resistance.  That seems like a departure for NICE relative to their guideline for the treatment of chronic neuropathic pain.  In that case the referral for specialty care was contingent on a specific prescribing consideration (opioids) and the pain specialist was considered the gatekeeper for opioid prescriptions in this situation.  Antidepressants are seen as overprescribed drugs but no gatekeeper is necessary.  I suppose the argument could be made that there are not enough psychiatrists for the job, but are they really fewer than pain specialists who prescribe opioids for chronic neuropathic pain in the UK?  

This model is only a slight variation on the Minnesota HMO model of screening everyone in a primary care clinic with a PHQ-9 and treating them as soon as possible with antidepressants.  The driving factor here is cost.  With a month of citalopram now costing as little as $4.00 - there is no conceivable low level psychosocial intervention that is more "cost effective".  I have also been a proponent of computerized psychotherapy as a useful intervention and it is not likely that the Information Technology piece needed to deliver the psychotherapy would be that inexpensive.  Another well known correlate of depression in the elderly is isolation and loneliness.  I was not surprised to find that there were no interventions to target those problems since it would probably involve the highest cost.  In the article standard research proven psychotherapies were recommended on par with the medical treatment of depression, but the question is - does anyone actually get that level of therapy anymore?  My experience in assessing patients who have gone through it is that it is crisis oriented and patients are discharged at the first signs of improvement.  That may happen after 2 or 3 sessions.

I doubt that the stepped care approach will do very much to curb antidepressant prescribing.  This study suggests that overprescribing is a problem using a strict indication of major depression.  There are always problems with how that is sorted out.  I have not seen any studies where a team of psychiatrists goes into a primary care clinic and does the typical exhaustive diagnostic assessment that you might see in a psychiatric clinic.  It would probably be much more relevant to the question at hand than standardized lay interviews or checklists.  There is also a precedent for interventions to curb over prescribing of medications and that is the unsuccessful CDC program to reduce unnecessary antibiotic prescriptions.  If clear markers of a lack bacterial infection can be ignored, what are the chances that an abstract diagnostic process will have traction?

And finally the stepped care interventions seem very weak.  This is a good place for any number of professional and public service organizations to intervene and directly address the psychosocial aspects of depression in the elderly.  Public education on a large scale may be useful.  The psychoeducation pieces can be included in relevant periodicals ahead of time rather than as a way to avoid the use of medications.  Environmental interventions to decrease isolation and loneliness is another potential solution.  From a medical perspective, if the concern is medication risk every clinic where antidepressants are prescribed should have a clear idea of what those risks are and how to assess and prevent them.  Patients who are at high risk from antidepressants should be identified and every possible non medication intervention (even the moderately expensive ones) should be exhausted before the prescription of antidepressant medication.   Primary care prescribing patterns that potentially impact the patient on antidepressants should also be analyzed and discussed.  A focus on risks and side effects can have more impact on the prescription of antidepressants than psychosocial interventions and waiting for the depression to go away.


George Dawson, MD, DFAPA


Supplementary 1:  Permission and credit for the graphic:

"From New England Journal of Medicine, Ramin Mojtabai, Diagnosing depression in older adults in primary care. Volume No 370, Page No. 1181, Copyright © (2014) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society."