09:10 AM

467 - Depression Management, Postviral Olfactory Dysfunction, Uncertainty

Take 3 – Practical Practice Pointers©

From the Department of Defense (DoD)/Veterans’ Administration (VA)

1)  Depression Management Guidelines Update


The DoD and VA produce well-done guidelines using the National Academy of Medicine’s “Guidelines We Can Trust” recommendations and the GRADE evidence rating system. They have updated their depression guideline recently and I have selected only some highlights here that are most applicable to primary care.

For patients with MDD who are being treated in the primary care setting, we recommend the use of collaborative/integrated care models.Strong for

We recommend that MDD be treated with either psychotherapy

or pharmacotherapy as monotherapy, based on patient preference. Factors including treatment response, severity, and chronicity may lead to other treatment strategies, such as augmentation, combination treatment, switching of treatments, or use of non–first-line treatments.

Strong for

When choosing psychotherapy to treat MDD, we suggest offering one of the following interventions (not rank ordered):

Acceptance and commitment therapy, behavioral therapy/behavioral activation, cognitive behavioral therapy, interpersonal therapy, mindfulness-based cognitive therapy, problem-solving therapy, or short-term psychodynamic psychotherapy.

Weak for
For patients with mild to moderate MDD, we suggest offering clinician-guided computer- or internet-based CBT either as an adjunct to pharmacotherapy or as a first-line treatment, based on patient preference.Weak for
When choosing an initial pharmacotherapy, or for patients who have previously responded well to pharmacotherapy, we suggest offering one of the following (not rank ordered): bupropion, mirtazapine, a serotonin–norepinephrine reuptake inhibitor, trazodone, vilazodone, or vortioxetine, or a selective serotonin reuptake inhibitorWeak for
For patients with MDD who achieve remission with antidepressants, we recommend continuation of antidepressants at the therapeutic dose for ≥6 months to decrease risk for relapse.Strong for
For patients with mild to moderate MDD who are breastfeeding or pregnant, we recommend offering an evidence-based psychotherapy as a first-line treatment. In patients with a history of MDD before pregnancy who responded to antidepressant medications and are currently stable on pharmacotherapy, weigh risk–benefit balance to both mother and fetus in treatment decisions.Strong for

Additional weak recommendations are made for some adjunctive treatments: exercise (yoga, qi gong, tai chi, resistance, aerobics), CBT-based bibliotherapy (self-help books), and standardized St. John’s wort extracts for mild depression (in patients who are not pregnant or lactating). The report comes out strongly against the use of MDMA, cannabis, and deep brain stimulation outside the research context.

John’s Comments:

The guideline is pretty readable, so it makes for a good refresher on depression treatment. I was particularly interested in the recommendation for computer/internet-based cognitive behavioral therapy – and wonder if we might be able to expose more of our patients to CBT given a different medium than counseling. This review is a list of apps and web sites that may help, but the author of the review developed one of them, so caveat lector!


·         McQuaid JR, Buelt A, Capaldi V, et al. The Management of Major Depressive Disorder: Synopsis of the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline. Ann Intern Med. Published online September 20, 2022. Link


From the Literature and a Question From a Colleague

2)  Recovery of Smell and/or Taste Post COVID-19 Infection



“I’ve had many patients who have experienced altered smell and taste after a COVID infection but a few who still haven’t recovered after more than a year.  How might I advise them?”


According to the 2016 US National Health and Nutrition Examination Survey (NHANES), 12% of adults > 40 experience some olfactory dysfunction for multiple reasons, including 3% having either anosmia (complete loss of smell) or severe hyposmia (decreased sense of smell).  Similar data is not available for those with hypogeusia (diminished taste function) and ageusia (absent taste function).

Sudden loss of taste or smell can occur in the setting of a current or recent viral upper respiratory infection (known as postviral olfactory dysfunction or PVOD).  In the context of COVID-19 infection, this has been particularly true for infections with the alpha and delta variants of the SARS-CoV-2 virus. 

Recently, the 3rd of a series of papers was published regarding altered smell and taste associated with mild COVID-19 infection in a cohort of 202 patients in Italy who were surveyed using structured questionnaires during the acute phase of their illness as well as after 4 weeks, 8 weeks, 6 months, and now at 2 years.  The aim of the present study was to estimate the 2-year prevalence and recovery rate of smell or taste dysfunction in the same series of patients.  The authors were able to follow 83% of the initial cohort through all 2 years.  They found that 64% had altered sense of taste or smell at baseline, 38% at 4 weeks, 17% at 8 weeks, 16% at 6 months, and 8% at 2 years.  Of note, at the 2-year follow-up, the most frequent nonchemosensory symptoms were fatigue (19%) and shortness of breath (11%).  Overall, the persistence of at least 1 symptom at 2-year follow-up was reported by 28% of the cohort. 

Mark’s Comments:

Remember, all those infected were with the alpha variant and would have been before any vaccine was available.  Regardless, for those who experience this, it can lead to significant distress.  I have a group of patients who have had long-term partial loss of smell/taste, as well as a relative who has experienced a persistent altered sense of smell, including that peanut butter now smells like gasoline. 

It should be noted that there is likely a gap between subjective perception and objective measurement of smell or taste deficits, with the rate of objective deficits in small studies being lower.  The good news is that the vast majority of smell and taste disorders associated with COVID-19 do not appear to be permanent. 

For those persons who are experiencing PVOD, consideration should be given to olfactory training.  This involves deeply sniffing at least four different odors for 10 seconds twice daily for at least 12 weeks (studies have been done up to a year). The odorants used are distinct and strong.  This training can be done at home, and, not surprisingly, preassembled “smell training kits” may be purchased, or vials of essential oils can be used for this purpose.  Studies have shown the use of an “olfactory training ball”  can help with adherence.  Very limited data indicate the use of budesonide nasal irrigation in addition to olfactory training may help with recovery. 


·         Boscolo-Rizzo, P et al.  Two-Year Prevalence and Recovery Rate of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19.  JAMA Otolaryngol Head Neck Surg. 2022;148(9):889-891. doi:10.1001/jamaoto.2022.1983 Link

·         Kronenbuerger M and Pilgramm M.  Olfactory Training.  StatPearls (Internet).  Last updated January 3, 2022.   Link.

From PeerRxMed ( www.PeerRxMed.org )

3)  How Certain Are You?


“Medicine is a science of uncertainty and an art of probability.”  Sir William Osler

For many years, I have found myself appreciating William Osler’s quote regarding medicine as being both a “science” and an “art” and acknowledging that much of what we do is filled with uncertainty.   Indeed, I have found myself seeing that the opposite of his quote is also true – when it comes to the practice of medicine, there is “science and art” to both uncertainty and to probability.  Yet applying both the art and science of uncertainty and probability to clinical practice is not as easy as this quote appears to make it. 

For example, this week I saw a woman in her 50s previously unknown to me who had been experiencing “chest pain” intermittently over the past several days.  While she had many cardiac risk factors, she also had many other "risk factors” for GERD as well as musculoskeletal pain, and both the history and exam were consistent with a non-cardiac source.  Her EKG was not normal, but the abnormality was consistent with some changes in the past with a subsequent “cardiac work-up” that was negative.  

Feeling convinced that this her pain was non-cardiac and that empiric treatment and “tincture of reassurance” was the appropriate next steps, I discussed my findings and recommendations with her.  She listened carefully and then posed the question that tends to pierce our clinical armor and leave us reflexively shifting into defensive mode by either going on a test-ordering spree or digging in emotionally to our position (or both):  “How certain are you doctor?” she asked. 

In that nanosecond of processing, somehow my mind found an alternative, wiser path, and rather than reactively feeling the need to answer her question, I responded with a question of my own.  “What has you most concerned?” I asked, expecting her to say that if I couldn’t be completely sure then more testing was necessary.  Instead, she answered, “I had a physician previously tell me when I had similar symptoms that if we couldn’t be absolutely sure, then we needed to do more tests.  I’d prefer not to do that as it caused both great discomfort and significant expense for me.”  I smiled and felt almost as if the spirit of William Osler was standing behind me, smiling as well.  “Yes,” I replied, “I can understand how that might have happened.  Let me tell you why I don’t think that’s necessary today.”  And she left satisfied with our plan. 

We live on the edge of uncertainty and precipice of probability every day in our work.  We don’t, however, often talk about how best to navigate it and the psychological toll that it can take.  Because of that, it can weigh us down without our even being consciously aware of it.  How about you?  How do you navigate the art and science of uncertainty and probability in your clinical work?  This certainly seems like a challenge (and even burden) worth exploring and sharing with a colleague, perhaps starting with your Buddy.  Afterall, in the world of professional uncertainty that we all navigate on a daily basis, no one should care alone.


Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org