Delirium Reinvented

One of my colleagues posted an article from the The Atlantic on delirium to her Facebook feed a few days ago.  Most of my colleagues in that venue are hospital, consultation-liaison, addiction or geriatric psychiatrists and we diagnose a lot of delirium.  Entitled the Overlooked Danger of Delirium in Hospitals it makes it seem like this is some kind of new and strange diagnostic category.  The article talks about the prevalence, the association with critical illness and advanced age, and the diagnostic overlap of dementia and delirium.  We hear from an Internal Medicine specialist Sharon Inouye, MD about the need to correctly diagnose and prevent delirium.  She mentions that as opposed to a decade ago, physician and nurses are all taught about delirium.  There is mention of the CAM (Confusion Assessment Method) that Inouye developed.  Like all health care articles there are estimates of the massive cost of delirium as well some prevention techniques.  There is also political concern that Medicare will declare delirium a "never" event with penalties for any hospital with cases of delirium.  That would be unfortunate because it makes a mistake that also seems to be made in this article - that delirium is a manifestation of many illnesses, especially the kind of illnesses that patient's are hospitalized for.

The article seemed odd to me because it was written from the perspective that delirium is an iatrogenic preventable event!  Certainly that can be the case. Delirium is a primary feature of hundreds of different disorders and recognizing delirium and those etiologies is potentially life saving.  Delirium can mimic psychiatric conditions due to the presence of hallucinations and delusional thinking.  For example, it is entirely possible to see a patient in the emergency department with apparent paranoid delusions and miss the fact that they happen to be delirious.  Sometimes the only sign is that the patient is inattentive and when vital signs are checked they have an elevated temperature.  This can be a common presentation of viral encephalitis in younger patients or urinary tract infections in the elderly.  It is bad form to miss either of those diagnoses and attribute the symptoms to a psychiatric disorder.  Another common form of delirium that is missed is drug or alcohol intoxication or withdrawal states.  Some intoxicants will render the patient totally unable to care for themselves until they are detoxified.  Other deliriums from alcohol or sedative withdrawal are life threatening and can be associated with seizures and other life-threatening states.  An acute change in a person's mental state resulting in delirium needs to be recognized and assessed as a medical emergency.    

One of the first cases of delirium that I ran into after residency was a case of cerebral edema that I was consulted on because of "hysterical behavior".  After that, I worked in and eventually ran a Geriatric Psychiatry and Memory Disorders Clinic for about 8 years.  The majority of people coming to that clinic had dementia of some sort.  They would see me and a neurologist.  We started out with an internist who was also a geriatric specialist, but that turned out to be overkill in terms of the number of medical specialists seeing each person in an outpatient clinic.  We eventually opted for records from the patient's primary care physician.  One of the most valuable functions of that clinic was our ability to follow people with prolonged deliriums.  Once a delirium has been established by a disease state and that state has resolved the delirium can persist for months.  Some of the outliers in that clinic took up to 6 months to clear.  We found that in many cases, the patients were extensively tested for intellectual ability and functional capacity when they were in the delirious state and told that they had dementia.  It was always instructive for the patient and family to get the testing repeated when we were sure the delirium had resolved and find that they had been restored to baseline.  Many people know their full scale IQ score and were relieved to see that they were back to that level of functioning.

A valuable lesson from working in that clinic and in hospital settings was the use of the electroencephalogram (EEG) as a possible test for delirium.   EEGs are commonly viewed as diagnostic tools to determine if a person is having seizures, but they also contain a lot of information about brain metabolism.  EEGs can be difficult to interpret especially if the patient is on a number of medications that affects cerebral metabolism. There are two broad categories of EEG patterns for delirium: one with a predominance of slow frequencies (designated theta and delta) and one with faster frequencies (designated beta).  We found a number of people with very significant cognitive impairment that was thought to be either a psychiatric disorder or a dementia but with a profound degree of slowing more consistent with a delirium.    

Delirium is an augenblick diagnosis for most psychiatrists.  The patient could appear disinterested, apathetic, agitated, or overtly confused.  It occurs in situations where brain physiology is compromised such as post surgical/anaesthesia states, drug intoxication states, drug reaction states, or possible physical illness delirium should be high on the differential diagnosis.  The Atlantic article makes it seem like knowledge about delirium is something very recent, but psychiatrists have been focused on it for a long time.  In the first two iterations of the DSM, delirium was subsumed under the categories of acute and chronic brain syndromes (DSM-I 1952) and organic brain syndromes (DSM-II 1968).  The current diagnostic code and name has been with us since the DSM III in 1980.  One of the early experts in delirium was Zbigniew J. Lipowski, MD, FRCP(C) - a Professor of Psychiatry from the University of Toronto.  His first text on the condition was Delirium: Acute Brain Failure in Man published in 1980.  That was followed by his classic text,  Delirium: Acute Confusional States published in 1990.  A comparable text from a neurological standpoint was Arieff and Griggs Metabolic Brain Dysfunction in Systemic Disorders published in 1992.

Any psychiatrist trained in the past 30 years should be able to diagnose delirium and come up with a differential diagnosis and monitoring or treatment plan.  A significant number of people can be followed on an outpatient basis as long as they are in a safe environment with the appropriate level of assistance.  The main goal of treatment is to make sure that the primary medical illness that led to the problem has been treated.  There are no known medications that will accelerate the resolution of these symptoms and medical management usually involves getting rid of medications that can lead to cognitive problems.  That can include benzodiazepines, antidepressants and antipsychotics but also more common medications like antihistamines and anticholinergic medications that are used for various purposes.  Like most psychiatric interventions in our health care system, clinics with staff interested in doing this work are few and far between generally because they are rationed resources.

There is a current movement underway to train Family Physicians and Internists (like Dr. Inouye) to recognize and prevent delirium.  In the minority of hospitals where psychiatrists work they are also a clear resource.  A delirium in a previously healthy person should signal a fairly comprehensive evaluation to figure out what happened.

And whenever there is a question of whether a person has a delirium or a psychiatric disorder - call a psychiatrist.  Psychiatrists know a lot about delirium and have for decades.



George Dawson, MD, DFAPA



Reference:

Sandra G. Boodman.  Overlooked Danger of Delirium in Hospitals.  The Atlantic.  June 7, 2015.


Supplementary 1:  The graphic is a standard EEG.  I tried to post a slowed EEG seen in delirium, but the publisher wanted what I consider to be an exorbitant fee for a non-commercial blog.  If anyone has a slow anonymous EEG laying around, send me a copy and I will post it.

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."

Pharmacosurveillance, Suicide and Antidepressants

I was board certified in geriatric psychiatry initially in 1991 and have been a member of the American Association of Geriatric Psychiatry since then.  Members receive the American Journal of Geriatric Psychiatry.  Treating depression in geriatric patients is a a very rewarding experience for psychiatrists because depression often masquerades as a severe medical problem like dementia, chronic pain, or Parkinson's disease.  Treating the underlying depression clears the manifestations that appear to be these other illnesses.  Even pure depression in an elderly patient can lead to significant medical compromise because of diminished physiological reserve and rapid compromise of nutrition or mobility as the result of sleep deprivation and inadequate intake.  That can occur as the result of discontinuing long standing antidepressant maintenance therapy.  The elderly also have some of the highest rates of completed suicide and that also factors in decisions about maintenance antidepressant treatment as well as effective psychosocial interventions to address that problem. 

In the January edition of the AJGP, Erlangsen and Conwell look at the relationship of completed suicide and antidepressant redemption in a nationwide cohort in Denmark.  The methodology of this study is not available in the United States.  Denmark has several registers based on a unique personal identifier for all of its citizens.  The authors looked at the Register of Medicinal Product Statistics and suicide as a cause of death in the Registry of Causes of Death for a cohort of people who were 50 years of age or older on January 1, 1996 through December 31, 2006.  Data on antidepressant use was identified and classified into tricyclic antidepressants, selective serotonin reuptake inhibitors and other types of antidepressants.  A treatment episode was considered to have occurred if a second prescription of antidepressants was filled and the patient appeared to be taking 0.75 tablets per day.

In terms of sheer number the study included 1,222,941 men and 1,346,973 women.  In the follow up period deaths by suicide numbered 3,061 men and 1,456 women.  As illustrated by Figure 1. below there is a decreasing number of those dying by suicide who redeemed antidepressant prescriptions.  In the 80+ year olds it was less than one in four women and less than one in eight men.  Trends were noted that percentage of men and women dying of suicide who took antidepressants decreased with increasing age.  This data is consistent with previous data that show that most elderly patient die by suicide are not in treatment at the time and they have clinically significant symptoms of depression.         

 (graphic removed by copyright manager - please see the original article)

This study is a good example of what kind of data is available with large databases across entire populations.  The limitations of the data are discussed by the authors including the fact that the pharmaceutical registry does not have any diagnoses and antidepressants have numerous indications.  They discuss why antidepressant redemption may not be the optimal proxy for antidepressant use.  In this case their study design considering only people who have redeemed the second antidepressant prescription to be in treatment.  That contrasts with some data suggesting the highest risk for suicide may occur in the initial days or weeks of antidepressant treatment.  They point out the usual qualification about association versus causality, but also conclude that "it is possible that antidepressants protect the oldest old from death by suicide" and point out the important public policy question of how to identify these patents.

There is a similar interesting study available that looks at a database that includes 3/4 of the population of the Netherlands (see reference 2).  It looks at the correlation between antidepressant use and both suicide and violence and concludes that there are significant negative correlations with both.  In other words increased antidepressant use led to decreased rates of suicide and violent behavior over the years 1994-2008.

When I read this study, I was also interested in what medical specialty is prescribing the bulk of the antidepressants.  I e-mailed one of the authors and asked that question.  The response was that the specific specialty of the prescriber was unknown but that bulk of antidepressants in Denmark were prescribed by primary care physicians and the likelihood of antidepressant prescription by primary care increases with patient age.  Psychiatric consultation was more likely to occur at a younger patient age.

In the United States we need pharmaceutical registries similar to the Danish registry.  We need a more factual basis to evaluate issues of pharmaceutical use over time, complications of prescription drugs, over prescription of drugs, and adequate drug utilization.  For example, with the recent concerns about stroke risk factor reduction in the elderly and stroke risk reduction from atrial fibrillation graphs similar to Figure 1. looking at all of the relevant medications may prove very useful.  Practically all pharmacy data in this country is proprietary and the largest database was developed to see if pharmaceutical representatives were having an impact on prescriptions written by individual physicians.  The  current development by individual states focused on the prescription of controlled substances is an opportunity to expand that data to identify important public health trends and reduce speculation.
  

George Dawson, MD, DFAPA

Figure 1. is reprinted from Am J Geriatr Psychiatry 2014 Jan; 22(1) Erlangsen A, Conwell Y. Age-related response to redeemed antidepressants measured by completed suicide in older adults: a nationwide cohort study, with permission from Elsevier. 

1:  Erlangsen A, Conwell Y. Age-related response to redeemed antidepressants measured by completed suicide in older adults: a nationwide cohort study. Am J Geriatr Psychiatry. 2014 Jan;22(1):25-33. doi: 10.1016/j.jagp.2012.08.008. PubMed Central PMCID: PMC3844115

2:  Bouvy PF, Liem M. Antidepressants and lethal violence in the Netherlands 1994-2008. Psychopharmacology (Berl). 2012 Aug;222(3):499-506. doi: 10.1007/s00213-012-2668-2. Epub 2012 Mar 7. PubMed PMID: 22395429; PubMed Central PMCID: PMC3395354