Airborne Transmission - Once Again!

 

I thought I would take time for a rare celebration on this blog.  Most of my writing is about probabilities and uncertain outcomes. In many cases I am responding to the same tired arguments from people who don’t understand science, biology, medicine or psychiatry. Those positions generally result in some political attacks based on that lack of understanding or some specific political agenda. The position I am referring today is the airborne transmission of viruses. Although it seems like a straightforward scientific issue it has led to as much controversy as any psychiatric topic. Despite a significant amount of literature out there on airborne spread, there has been nothing but resistance to the concept.

Nowhere was the resistance more evident than the advent of the current SARS-CoV-2 pandemic. Initially the message was that the virus was spread by fomites or intermediate size droplets that fall within a few feet following a cough or a sneeze.  Accordingly, social distancing at more than a few feet, decontaminating hands and surfaces were recommended to counter this mechanism of transmission. Many experts claim that most respiratory viruses with very few exceptions are transmitted this way. Those same experts claim that airborne transmission of viruses in smaller droplets travelling much longer distances was controversial at best. All of those conflicting ideas led to recommendations for no masks in February of 2020 followed by recommendations for masks in the next two months.  The mask recommendations occurred in the context of widespread shortages of personal protective equipment (PPE) for health care workers.   

I posted my qualifications on the matter (2 Avian Influenza Task Forces earlier in this century, being subjected to multiple respiratory virus epidemics at work despite rigorous hand washing, and studying the available engineering and viral data, and lengthy discussions with HVAC experts) and began to write about it on this blog.  My perspective is clearly that respiratory viruses are airborne and therefore will not be stopped by handwashing alone, that there are clearly engineering approaches to stop respiratory viruses that will work much better than just handwashing, and that there should be a major research and development effort on environmental designs to minimize and even stop respiratory viruses in homes and public building. In fact, as I type this I have selected a UVC device to be installed in my home HVAC system and it will probably be installed in the next month or two.  Many of those posts on this blog can be found here or by using the search term “airborne” in the search box.

The victory lap today occurs with a press release from the CDC today that I consider a bombshell in terms of the airborne transmission concept.  The press release is a quick read but it highlights why surface contamination is unlikely to be a significant factor:

“Quantitative microbial risk assessment (QMRA) studies have been conducted to understand and characterize the relative risk of SARS-CoV-2 fomite transmission and evaluate the need for and effectiveness of prevention measures to reduce risk. Findings of these studies suggest that the risk of SARS-CoV-2 infection via the fomite transmission route is low, and generally less than 1 in 10,000, which means that each contact with a contaminated surface has less than a 1 in 10,000 chance of causing an infection.”

And further:

“The principal mode by which people are infected with SARS-CoV-2 is through exposure to respiratory droplets carrying infectious virus.”

This information has been slowly presented over the course of the past several months.  For example, Dr. Fauci mentioned on several news outlets that cleaning all of the mail and groceries was not necessary because it was not considered a main route of transmission. A logical inference from that statement is why there is a concern about any surfaces at all unless there is a person with a known infection close by.  And by extension, if surface contamination is not that much of a problem why the concern about accidentally touching your face?  As Dr. Fauci typically states we now have the science behind the transmission and the recommendations can be adapted to the new findings.

The CDC press release does not come right out and say airborne transmission.  They continue to say respiratory droplets are the predominate mode of spread and the old document on respiratory droplets says nothing about differentiating between moderate sized droplets that typically fall to the ground within a 6-foot radius of where they are generated or airborne droplets that are lighter, spread past 6 feet from the generation site and remain suspended for longer periods of time.

Some of the comments on the press release have been much more definitive. The only reference to this post has a good timeline on the airborne controversy and this quote from atmospheric chemist Jose-Luis Jimenez: “If we took half the effort that’s being given to disinfection, and we put it on ventilation, that will be huge.”  In the same reference Germany has invested a half billion dollars in improving ventilation and indoor air quality.

Overall, it appears that the CDC is slowly coming around to the idea that respiratory viruses are transmitted via airborne routes, but some resistance is still evident in the press release they link to an earlier non-descript respiratory droplet transmission document.  There are many potential advantages to fully backing the airborne transmission concept (in addition to the available science).  Research and development is at the top of the list. In an early blogpost, I pointed out that UV decontamination was routine in buildings when I was a kid in a small town in northern Wisconsin.  The currently available UVC is much safer and very effective for killing airborne biological particles. From a clinical trials perspective, deployment of these systems on a large scale and following the number of respiratory infections in facilities with and without the technology seems like a fairly basic experiment.

It is also interesting to consider the resistance. There is undoubtedly politics in science and that can be a factor. There may be a medical intervention bias. In other words, we need some magical intervention like a vaccine, antiviral medication, or general polypharmaceutical modality that can either cure or prevent the excessive morbidity and mortality from respiratory viruses.  The track record there is some wins and many losses.  Every year various populations around the world are subjected to significant effects from flu-like illness that are nowhere as lethal as SARS-CoV-2.  Remarkably – everyone accepts this state of affairs until a more lethal virus comes around and affects a larger group of people.  There is politics as usual leading to irrational attitudes about viruses and physical interventions.  The appropriate environmental interventions may make mask refusers irrelevant at some point in the future.

The bottom line of today’s release is good news for all of the airborne virus crowd and I definitely consider myself in that crowd. I would still like to see the CDC modify their position on transmission in respiratory droplets and I think that is coming.  But most of all, I would like to see us get serious about using environmental measures to limit the exposure and spread of all respiratory viruses including the current one that has killed far more Americans than any influenza epidemic since 1918.

 

George Dawson, MD, DFAPA

 

References:

1:  Lewis D. Why indoor spaces are still prime COVID hotspots. Nature. 2021 Apr;592(7852):22-25. doi: 10.1038/d41586-021-00810-9. PMID: 33785914.

2: Dietrich WL, Bennett JS, Jones BW, Hosni MH. Laboratory Modeling of SARS-CoV-2 Exposure Reduction Through Physically Distanced Seating in Aircraft Cabins Using Bacteriophage Aerosol — November 2020. MMWR Morb Mortal Wkly Rep. ePub: 14 April 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7016e1

3: Greenhalgh T, Jimenez JL, Prather KA, Tufekci Z, Fisman D, Schooley R. Ten scientific reasons in support of airborne transmission of SARS-CoV-2.  The Lancet (online).  Published 4/15/2021. https://doi.org/10.1016/S0140-6736(21)00869-2  Current link

4: Tang JW, Bahnfleth WP, Bluyssen PM, Buonanno G, Jimenez JL, Kurnitski J, Li Y, Miller S, Sekhar C, Morawska L, Marr LC, Melikov AK, Nazaroff WW, Nielsen PV, Tellier R, Wargocki P, Dancer SJ. Dismantling myths on the airborne transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Hosp Infect. 2021 Apr;110:89-96. doi: 10.1016/j.jhin.2020.12.022.  Current Link

Medical Library Access For Everyone

 

Medical library access is a critical issue for physicians because only a few physicians have access to all of the literature that they need.  For as long as I have practiced medicine and psychiatry life long learning has been a stated goal of the profession.  That forms not only professional behavior but it is also incorporated into the medical practice laws of each state.  In order to be relicensed each year, medical practitioners also have to fulfill the continuing medical education (CME) requirements in each state.  That typically requires a combination of self-study and CME courses sponsored by various medical education organizations typically departments of psychiatry or professional organizations.

When I first came to the Twin Cities in 1989, I worked for a large multi-disciplinary clinic in St. Paul, MN.  We were the second largest hospital-based practice in the Twin Cities and a Level 1 Trauma Center and Burn Unit.  We had the most psychiatry beds in the East Metro area. I did a rotating internship at this hospital and liked the practice and the attendings well enough to return there and stay for the next 22 years. We also were a teaching hospital and trained medical, surgical, and psychiatric trainees from the University of Minnesota.  As a result of that position, I was expected to train resident physicians and medical students. At some point we were given electronic access to the Biomedical Library at the University of Minnesota and could access a wide array of biomedical journals online at that facility.  Up to that point, I had to go to the library and make copies of articles that I wanted to study and keep for future reference.  I was also able to access interlibrary loan articles through my hospital library that I would get via mail or fax in 2-3 days.  All of this reference material was relevant to my clinical work, teaching, and research at the hospital.

In general, University training programs depend on their affiliated or adjunct staff and facilities for teaching residents.  These affiliations result in broader clinical exposure to both patients and practitioners as well as different work environments. Good examples of the necessity of these affiliations is the amount of individual and psychotherapy supervision residents require.  Much of that training is provided by practitioners in the community who are doing the work every day.  In some cases a University training program may lack a critical component like an addiction service or a community psychiatry service and these affiliations provide those resources.  In return for the services provided to the training program, the affiliated practitioners get University titles and electronic access to the library.  In todays work environment stressing excessive productivity, there is generally no break in the work of the day.  For example, the adjunct teachers are still required to put in a full day’s work in addition to their teaching and supervisory role.  All of the work for the training program is uncompensated with the exception of the access to the library perk.

In my case, the other physicians in my group had negotiated with the University so that we all had regular Assistant Professor titles. We understood our role was critical to the components of the educational program and that these titles had nothing to do with regular track university titles.  As time went by our group was acquired by a managed care company and the teaching role diminished.  There was some turmoil at the University and a non-psychiatrist was appointed temporary department head. He ended up sending out letters firing numerous adjunct faculty – myself included.  The letter stated that we were "costing the department too much" as the rationale for the “firing”.  Since I was curious about how much I could be costing, when I had not ever been compensated – I called the University and asked them that question.  The answer was a $1,000/year library access fee. When I got that figure I called the University library and asked them if I could retain library access by paying them $1,000/year and they declined giving no good reason other than "it is policy".

To establish how much an individual physician may expend on journal resources – I include my subscriptions below.  The total cost is $2,640/year for a very inefficient way to access articles of interest.  Some are more inefficient than others. For example, my APA membership includes 1 of a possible 5 journals.  Just a few years ago it included at least an additional journal, but now the other journals are all for addition fees.  By comparison – the AMA membership includes access to 11 journals for only slightly more money.  Getting all of these journals to read only a fraction of the articles is also very inefficient.  The educational and self-improvement goals of individual physicians depend a lot on medical specialty and current practice environment as well as how much interest they have in the biology relevant to that specialty. Early in my career I was in a research position where we all got a hard copy of Current Contents, checked off the articles of interest and got the reprints within a day or two.

Another level of inefficiency is introduced at the level of publishers.  If you think about it medical publishing is a relatively low-cost endeavor.  Publishers are not paying for content. All of the submissions to their journals are generated for free by scientists and physicians wanting them published.  The peer reviewers who expend significant amounts of time reviewing these articles are not reimbursed.  The costs are basically for a small editorial staff, maintaining an information technology (IT) infrastructure and Internet presence, and printing paper journals.  Ideally, paper journals could be eliminated and readers could access the electronic copies and read and print what they want. We are not in the ideal world at this point. Many if not most publishers do not provide access to electronic only journal copies.

Licensing agreements between publishers and services that aggregate publications is also a controversial area. Publishing has become a very high margin business, particularly if that publisher has a number of widely read journals. In some of these cases, the annual licensing fees are easily in the millions of dollars per year for large university facilities.  That has led some library facilities to refuse or threaten to refuse agreements with major publishers so that their journals cannot be accessed.

Given this landscape, is there a possible solution that resolves the physicians need for eclectic reading, the state’s interest in physicians with life long education, the library’s interest in providing a useful service to its patrons, and the publisher’s interest in being paid.  I think there is and that is to make the University medical library electronic services available to anyone willing to pay an agreed upon fee. I was willing to pay $1,000/year 12 years ago and I am clearly paying much more for limited individual access to the journals listed in the table below.  Basically, the state and the library’s ability to negotiate group access will makes it more widely available to more physicians or for that matter anyone in the state who wants the equivalent access to electronic journals.

There are alternatives to paid journals for access.  Some grant recipients need to provide a free copy of their paper that is posted as open access on the National Library of Medicine web site (in their PubMed search engine). There are open access journals, many of which charge the authors a publication fee.  I was an editor for one of these journals and came away from that experience with the perspective that it adds significant conflict of interest for the publisher and may encourage the publication of low-quality research for profit. There are many high-quality journals that have added a smattering of open access papers for one reason or another. During the current pandemic many high-quality journals have offered articles relevant to the pandemic as open access. There are also research sites where authors can be contacted to request papers and pre-print servers where you can read the unedited versions. All of these indirect measures assure some level of access to articles that might be behind a paywall, but it is no guarantee.  For example, my requests to researchers are successful about 50% of the time and in many cases, they tell me they are prohibited from sharing their research due to copyright constraints.  The only way that you can review the literature for writing or research purposes is with complete access to what is out there.

At some point I am hopeful that physicians and/or their professional organizations advocate for these services.  

George Dawson, MD, DFAPA

Graphic Credit - Shutterstock per their standard agreement.  Click on any graphic to expand.

The New Black Box Warnings On Benzodiazepines

 

 

The FDA started communicating that there was going to be a new black box warning in the package inserts of benzodiazepines starting last fall.  Black box warnings are defined as applying to potential problems with medications that can lead to serious or life-threatening complications.  These warnings have been around since 1979 and they are included in the package insert or detailed prescribing information included with every medication. They are also available on line by searching “[drug name] FDA package insert”.  The changes in the package insert for benzodiazepines (in this case diazepam and clonazepam) are shown in the graphic at the top of this page. In this case the old package insert is on the left and the new one that I received in the mail on March 18, 2021 is on the right.

Benzodiazepines are controversial medications and have been over most of their 60-year existence.  Current benzodiazepines and z-drugs that are primarily used for sleep and their release dates are listed in the graphic below:

At the time of their original release the primary indication for the medication was anxiety (although current diagnostic nomenclature was not in use at the time) and that continued to be the main indication until the advent of higher potency benzodiazepines like clonazepam, lorazepam, and alprazolam. Higher potency benzodiazepines were used for panic disorder and panic attacks. As clinical use expanded it became clear that these medications also reinforced their own use and that people could develop a substance use disorder with all medications in this class.  They were also noted to be cross tolerant with alcohol and other sedative hypnotics so that the use of benzodiazepines expanded to detoxification applications.

When it became apparent that some people were not able to stop using benzodiazepines, escalated the dose, or began acquitting them from non-medical sources strategies were developed to minimize their use as much as possible.  The following timeline looks at how the treatment guidelines for anxiety and panic changed over the years with the goal of minimizing benzodiazepine exposure.

The graphic illustrates that benzodiazepines have gone from a primary role (and in some case very high dose role) in the treatment of panic disorder to a secondary and time limited role.  Clinical prescribing typically expands on the original FDA approved indications. In the case of benzodiazepines, it is common to see them prescribed for various types of situational anxiety like public speaking or air travel.  It is also very common to see them prescribed for both transient emotional disorders (from a time limited stressor) and ongoing emotional disorders from chronic stressors.  In society today there is always a performance enhancement aspect. A common example is the person who consumes a lot of caffeine in the daytime to stay energetic and alert at work and in the gym who needs to take a benzodiazepine to treat the expected insomnia.  The main problem in prescribing the medication to a benzodiazepine naïve patient is that it is not possible to predict with certainty how they will respond.  With any medication that reinforces its own intake a substantial number of people will stop taking to due to side effects – typically excessive sedation or cognitive problems. Patients at risk with notice a euphorigenic effects that is very reinforcing.  A large number of people will take it as prescribed. In my experience, fewer people will take benzodiazepines if they receive informed consent that they are a potentially addictive medication.

The move to benzodiazepines by psychiatrists and primary care physicians came after decades of using medications with a much lower therapeutic index – primarily barbiturates but also meprobamate (Miltown) and ethchlorvynol (Placidyl). For the initial decades of use, it was taught that it was nearly impossible to ingest a lethal overdose of benzodiazepines unless they were combined with alcohol.  

Withdrawal effects with benzodiazepines can also be significant.  They depend on the duration of use, dose of medication, and pharmacological properties of the medication. In the most severe case, withdrawal delirium or withdrawal seizures can occur and both are potentially life-threatening situations compounded by the lack of effective treatment facilities.

From an epidemiological standpoint, one question is what is the current level of benzodiazepine use and is it changing over time?  Are there any direct measures of prescriptions rather than proxies like overdose deaths or benzodiazepine-based office visits?  There is a business that does collect prescriptions in retail pharmacies and has done that for the past 60 years. That data is proprietary and tends to be available only in glimpses where it is referenced by the purchaser.  In all of my searches on this subject, I located an FDA presentation on prescription patterns of controlled substances (3).  In the benzodiazepine section of that presentation there are a fairly consistent 20 million prescriptions per year between 2009 and 2015.  The commonest prescribed benzodiazepines were alprazolam (50-60%), lorazepam (25%), and diazepam (10-15%).  Further analysis shows that about 75-80% of all these prescriptions were from non-psychiatric physicians and 15% by psychiatrists and 15% by nurse practitioners and physician assistants.  67% of all benzodiazepine prescriptions were for women.  By age demographics 80% of all prescriptions were to people who were 40-59 (41.4%) and 60+ (38.2%).  This information is interesting because there is a life stage correlation with increased benzodiazepine use and use by the oldest demographic that has been flagged in the geriatric literature as being higher risk because of falls and cognitive impairment.

A global perspective on benzodiazepine use is available from INCB (International Narcotics Control Board) who estimates global supply and demand for controlled substances across the world.  According to that report, global production in 2018 was 199 tons and increase of 24% from 2017 (p. 36). The INCB also estimates the total benzodiazepine use by country for clinical and scientific use.

Additional resources in this area include this post that looks at a selective study of several states that agreed to disclose prescription levels for the purpose of this study.  There is significant variation in both opioids and benzodiazepine use from state to state.  My initial thoughts about pharmacosurveillance and pharmacovigilance still apply.  A robust system of following medication side effects and utilization can no longer depend on inadequate snapshots and voluntary reporting.

With regard to the specific change in black box warning the three main bullet points are all very reasonable and I would be shocked if any physician is not aware of these problems.  The first bullet point, highlights that the epidemiology of overdoses clearly shows a correlation of deaths with concurrent use of benzodiazepines and a shift to more potent fentanyl based illicit opioids.  A trend that has not received any comment yet is the use of fentanyl to produce counterfeit benzodiazepine tablets.  The second bullet point is necessary for the informed consent discussion with any patient.  Unless the addictive potential is openly discussed patient concerns about their past experience with addictive drugs and their family history is never mentioned.  The severity of addiction and withdrawal effects including the potential for protracted withdrawal also need to be openly discussed. The third bullet point is basically a necessary extension of the warning about tolerance and withdrawal. In clinical practice it is common to talk with patients who decided that they wanted to discontinue benzodiazepine on their own and experienced seizures and/or severe withdrawal after abrupt discontinuation.

The associated concern about the black box warning is whether it will change physician behavior or not. The experience with the black box warning on antidepressants and suicidality in patients less than 25 years of age had a significant effect on decreased prescriptions in that age group. The black box warning on benzodiazepines is really nothing new and it will be interesting to see if there are any effects. The lack of comprehensive prescription information restricts any study of that phenomena to local effects. A useful outcome may be a more comprehensive discussion of the risks and benefits before benzodiazepines are prescribed.        

 

George Dawson, MD, DFAPA

 

References:

1:  Silberman E, Balon R, Starcevic V, Shader R, Cosci F, Fava GA, Nardi AE, Salzman C, Sonino N. Benzodiazepines: it's time to return to the evidence. Br J Psychiatry. 2021 Mar;218(3):125-127. doi: 10.1192/bjp.2020.164. PMID: 33040746.

2:  Balon R, Starcevic V, Silberman E, Cosci F, Dubovsky S, Fava GA, Nardi AE, Rickels K, Salzman C, Shader RI, Sonino N. The rise and fall and rise of benzodiazepines: a return of the stigmatized and repressed. Braz J Psychiatry. 2020;42(3):243-244. doi: 10.1590/1516-4446-2019-0773. Epub 2020 Mar 9. PMID: 32159714; PMCID: PMC7236156.

3:  Jones CM.  The latest prescription trends for controlled prescription drugs. FDA presentation. September 1, 2015

4:  International Narcotics Control Board.  Psychotropics 2019 Statistics for 2018 Assessments of Annual Medical and Scientific Requirements.  Link.

Graphics:

All graphics made by me.  As far as I know package inserts are public information. Click on any graphic to enlarge.

Brain Fog

 

“Brain fog” or “brain-fog” is a popular term that has penetrated the medical literature fairly recently.  In talking with hundreds of patients who have used the term in my evaluations most of them mean an actual fogginess to their mentation.  That typically occurs in two ways. The first is an underwater feeling and noticing that both the speed and content of thought is not quite up to par.  The second is more of a problem in concentration and focus where it takes a noticeable effort to sustain both.  I have personally had these experiences during illness and probably on a developmental basis.  In the case of the illness, I was running my usual team meeting at about 8AM, and suddenly realized my thoughts were clouded. I developed chills and knew that there was a mini-epidemic of influenza in my staff. I told my team members that I had to stop due to illness and went home.  It took about 48 hours for that to clear.  Since that time, I have been very interested in how infectious diseases and diseases in general have that effect on the brain.

The closest term that I could think of that might approximate brain fog is “clouding of consciousness”.  This term from descriptive psychiatry and psychopathology is commonly associated with neurocognitive disorders. It is typically a criterion for delirium but in most texts, it is also associated with other anatomical and functional brain disorders.  The best review of the psychopathology and phenomenology of clouding of consciousness is from Lipowki’s text (1).  Lipowski reviews the 2500 year history of delirium and how confusion and clouding of consciousness became critical concepts in advancing research in this area.

A lot of the current psychopathology texts have very little to say about clouding of consciousness and symptoms of delirium.  There are a few exceptions.  Sims discusses it in a chapter “Consciousness and Disturbed Consciousness”.  He starts with defining consciousness by three components an inner awareness of experience, intentional reaction to objects, and knowledge of the conscious self.  He also has an excellent diagram (Fig 3.1 p. 40) that ties together the medical use of the term, clinical context, and changes that can occur in that context.  Since I cannot get permission to post the diagram I will describe it.  Normal consciousness is the central component and it is transitioned to reduced wakefulness, sleep, and stages of sleep and deep sleep.  There is another transition to the unconscious mind (via preconsciousness).  The final transition is to clouding of consciousness, drowsiness, stupor, and coma. The latter transition is obviously the only pathological one, but in terns of psychopathology there is obvious overlap between reduced wakefulness transitioning to normal sleep and drowsiness that may be a prelude to neurocognitive disorders.  That is also a critical decision point in thinking about brain fog.  Is the underlying mechanism one of reduced wakefulness or a focal or global decrease in brain metabolism seen in neurocognitive disorders?  Sims also defines clouding of consciousness as: “most intellectual functions are impaired including attention and concentration, comprehension and recognition, understanding, forming associations, logical judgement, communication by speech and purposeful action”. (p. 41).  Sims definition is most consistent with an early delirious state but not “brain fog” described by a person who is going to work every day and subjectively feels that their work performance could be better.

I have followed the evolution of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) across the last 3 versions of Lahita’s text on SLE.  There are generally 2 chapters dedicated to this topic in each text.   Over the years, there has been much more specificity in terms of the biological mechanisms involved in NPSLE.  There are 19 separate neuropsychiatric syndromes involving neurocognitive symptoms and constellations of more pure psychiatric symptoms like anxiety and depression.  From a purely cognitive standpoint, an interesting concept is that many of the mechanisms that are thought to moderate cognitive function like long term potentiation (LTP), synaptic plasticity, and neurogenesis are immune cells and inflammatory molecules.  The diagram below illustrates some upstream perturbations in the cytokine system that can result in impaired learning and memory.  There are additional immune systems affecting neurogenesis.

     

In the review that I constructed this diagram from, the author states: “‘‘Lupus brain fog’’ is an extremely common patient complaint that refers to periods of forgetfulness and confusion that are related to impaired cognition.”  She cites the range of 21-80% of SLE patients having some degree of cognitive impairment leading to some degree of disability or impaired quality of life.  NPSLE and the associated studies of how inflammation and immune function impair learning and memory is an excellent example of how various disease processes can have effects on cognition. It is also a good example of how the term “brain fog” has developed recently in this clinical population with clear CNS pathology.  It also suggests a lack of specificity for the term given the range of impairment.

At this point – a few clinical vignettes of “brain fog” can be considered as additional examples:

Vignette 1:  60-year-old man referred for assessment and treatment of mania and possible bipolar disorder.  He gives a history of drinking 750 ml/day of alcohol and appears intoxicated at the time of the evaluation.  As part of the initial evaluation, he is given a standard cognitive exam and scores a perfect 30/30 points indicating no deficits in orientation, attention span, short term memory or language skills (comprehension, repetition, or naming).  He has no subjective cognitive symptoms.  He returns a week later for reassessment and does not recall meeting the same physician or doing any cognitive testing. He does not believe he was ever at the clinic in the past.

This patient essentially blacked out or was amnestic for the initial interview with the psychiatrist.  Like many heavy drinkers he has a sustained mood disturbance at times that resembles manic episodes, but these symptoms resolve after detoxification and abstinence from alcohol. Patient with these problems are likely to described brain fog during episodes of intoxication, withdrawal, detoxification, sleep deprivation from the effects of alcohol, decreased attention span and concentration that is probably multifactorial and during mood changes that are alcohol induced.  Heavy alcohol consumption can lead to profound and persistent cognitive changes, most notable from untreated Wernicke encephalopathy the result of Vitamin B1 deficiency that can accompany persistent alcohol use.

Vignette 2: 40 yr old woman referred for assessment of severe anxiety and panic. She attributes both symptoms to “chronic Lyme disease” despite extended course of antibiotic treatment by experts and extended treatment by non-medical personnel using more atypical types of treatment.  She was previously very vigorous and physically active but that is no longer the case.  She describes fatigue, hypersomnia, and “brain fog” that puts her job at risk because of decreasing productivity and performance. She is being treated with benzodiazepines for anxiety and z-drugs for sleep.

This is a familiar scenario for psychiatrists. In this case the patient is diagnosed with a controversial illness and has not recovered despite very aggressive treatment.  She is anxious because of the decrease in her level of functioning and describes fatigue, hypersomnia, and brain fog.  It is often difficult to determine the progression of symptoms without detailed records – depending only on the patient’s recollection of what happened over a number of years.  In these cases I have found that it is best to track all of these symptoms and see how they fluctuate with logical changes based on the patients current clinical status. In these cases I would typically proceed with tapering and discontinuing the benzodiazepines and z-drugs and monitoring the fatigue, hypersomnia, and brain fog while simultaneously providing psychotherapy that I thought would be most effective for the target symptoms.

Vignette 3: 50 yr old man being seen for severe alcohol use disorder, persistent depression disorder, major depression, chronic insomnia, and possible attention- deficit/hyperactivity disorder. He has had lifelong insomnia, onset of chronic depression at age 18, and heavy daily drinking for the past 15 years. He describes inattentiveness, distractibility, procrastination, and “brain fog”.  He is requesting that treatment for the “brain fog” be prioritized since it is currently his most significant problem.

Very common scenario in treatment settings.  The ADHD diagnosis is more controversial lately based on the idea that some people may develop it as an adult.  I always ask adults about childhood sleep problems and it is a very common finding.  Childhood sleep disturbance also results in erroneous diagnoses of ADHD, but it is often difficult to establish that diagnosis in generations where it was not emphasized on school.  The diagnosis of alcohol use disorder is a complicating factor. In the case of heavy drinkers, they are often drinking all day long, in a state of intoxication or withdrawal, and typically wake up in the middle of the night and need to decide whether to drink in order to fall back asleep or tolerate withdrawal until the morning and then drink to reduce more severe withdrawal symptoms.  Clearly, every one of those transitional states is associated with some cognitive impairment and some have described it as “brain fog”.  An additional patient-based bias is wish that a medication can correct all of this cognitive impairment.  That wish is complicated by the fact that many heavy drinkers have used cocaine or amphetamines to drink more and improve their concentration and attention.  They have also used benzodiazepines as a way to treat insomnia and withdrawal symptoms, especially withdrawal symptoms in the morning that could otherwise lead driving to work with high blood alcohol levels and risking legal problems.  In all of these cases, the patient needs to be followed and serially reassessed up to the 60-day mark.  In my experience, the transient cognitive symptoms should be clear at that point and the baseline symptoms and their severity can be determined.

If brain fog exists can it be phenomenologically separated from other psychiatric diagnostic terms?  Sedation or excess somnolence is a common form of clouding of consciousness.  There is a temporal aspect to both related to a combination of both alerting mechanisms and circadian rhythms and the biological basis of both has been grossly determined (6).  I would anticipate that sedation or somnolence would fluctuate over the course of the day, with the exception excessive sleep deprivation or external sources of sedation like a sleeping agent.  Most people tend to describe brain fog as unrelenting.

In the final analysis, is brain fog a useful term?  Is it a colloquialism rather than a technical term that should be used in medicine? My argument suggests that it may be a useful descriptor of a sub delirious state or very early clouding of consciousness.  There are multiple associated etiologies and conditions including some that are just a temporary disruption in normal physiology.  Based on my clinical experience it is clearly a word that patients frequently use. From the PubMed search, it is also being used more frequently in the medical literature, just over the past 20 years. 

 

A word of caution is needed before it is adopted on any widespread basis. Lipowski points out how 19^th century psychopathologists advanced the field by specifying a class of disorders based on clouding of consciousness and confusion arising in the context of acute brain dysfunction.  What followed was a proliferation of terms that set back further research for decades (p. 27).  Time will tell if the term becomes more widely adapted or it is fitted into existing nomenclature.  Based on the recent tightening of the nomenclature for delirium (7) it is not likely.  Since most people seem to be using it to cover both mild and moderate subjective cognitive impairment - it does not add much precision. On the other hand psychiatrists are focused on the patient’s subjective state and use of language so it is undoubtedly useful for beginning the early exploration of the problem that led to the consultation.

 

George Dawson, MD, DFAPA

 

References:

1:  Lipowski ZJ.  Delirium: Acute Confusional States.  New York: Oxford University Press, Inc; 1990.

2:  Sims A.  Symptoms in the Mind: An Introduction to Descriptive Psychopathology. 3^rd ed. Amsterdam: Elsevier Limited; 2003.

3:  Mackay M, Ulug AM, Volpe BT.  Neuropsychiatric Systemic Lupus Erythematosus: Mechanisms of Injury.   In:  Lahita RG, Tsokos G, Buyon J, Kolke T.  Systemic Lupus Erythematosus. 5^th ed. London: Academic Press; 2011. p. 491- 512.

4:  Hanley J.  The Nervous System and Lupus. In:  Lahita RG, Tsokos G, Buyon J, Kolke T.  Systemic Lupus Erythematosus. 5^th ed. London: Academic Press; 2011. p. 727-746.

5:  Mackay M. Lupus brain fog: a biologic perspective on cognitive impairment, depression, and fatigue in systemic lupus erythematosus. Immunol Res. 2015 Dec;63(1-3):26-37. doi: 10.1007/s12026-015-8716-3. PMID: 26481913.

-Reference 5 is an excellent open access review of the relationship between inflammation, immune systems, and cognition (especially memory and learning).

6:  Valentino RJ, Volkow ND. Drugs, sleep, and the addicted brain. Neuropsychopharmacology. 2020 Jan;45(1):3-5. doi: 10.1038/s41386-019-0465-x. Epub 2019 Jul 16. PMID: 31311031; PMCID: PMC6879727.

7:  Slooter AJC, Otte WM, Devlin JW, Arora RC, Bleck TP, Claassen J, Duprey MS, Ely EW, Kaplan PW, Latronico N, Morandi A, Neufeld KJ, Sharshar T, MacLullich AMJ, Stevens RD. Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies. Intensive Care Med. 2020 May;46(5):1020-1022. doi: 10.1007/s00134-019-05907-4. Epub 2020 Feb 13. PMID: 32055887; PMCID: PMC7210231.

8:  Servick K. COVID-19 ‘brain fog’ inspires search for causes and treatments.  Science. 2021 Apr 27;372(6540):329. doi:10.1126/science.abj2105. 

Graphic Credit:

Graphic was downloaded from Shutterstock per their standard agreement.  The artist in this case had many similar brain fog graphics and these depictions are probably an indication of how common this term has become.

Here is an additional graphic that I complied as I did the literature search for this post: