Challenging Diagnoses, New Treatments, and Clinical Conundrums Discussed at Annual Meeting

Psychiatric TimesVol 38, Issue 6

The 2021 American Psychiatric Association Virtual Annual Meeting brought together leaders in psychiatry to discuss hot topics including diversity, COVID-19, mood disorders, and more.



Is It a Psychiatric Disorder or a TBI Medical Mimic?

by Heidi Anne Duerr, MPH

Too often, the medical issues associated with traumatic brain injury (TBI) are mistaken for psychiatric disorders, and patients are mistakenly referred to psychiatrists for treatment, Gregory J. O’Shanick, MDDLFAPA, told attendees.

O’Shanick, medical director of the Center for Neurorehabilitation Services in Richmond, Virginia, reminded psychiatrists to leverage their medical knowledge when assessing patients to help distinguish TBI-related medical mimics and true psychiatric diagnoses.

As the prevalence of TBI has increased, so too has research linking psychiatric disorders and TBI, O’Shanick said.1 Jennie Ponsford, PhD, and colleagues explored this phenomenon and found that only about 23% and 21% of individuals had a pre-TBI history of a mood disorder or an anxiety disorder, respectively.2 They found an increase in psychiatric symptomology within the first year after TBI; mood and anxiety symptoms were most common (prevalence, 17.2%-62.0% and 10.3%-34.2%, respectively). Interestingly, O’Shanick noted depression is 4 to 6 times more common in patients with TBI than in the general population, and it is the most common cause of depression in men.

It is possible, he explained, that some of these mood disturbances and anxiety symptoms may be better explained as a medical consequence of TBI—or a signal of homeostatic disruption. In such cases, providing psychopharmacological treatment might improve symptoms but will not address the underlying cause.

To illustrate this issue, O’Shanick discussed examples of phobias misattributed to psychiatric diagnoses. For instance, if an individual has unrecognized balance and visual issues as a result of TBI, they may feel a sense of anxiety when in crowds. Instead of recognizing that the uneasiness is due to stability issues, the person may inappropriately link the feeling to an anxiety disorder.

“As physicians, we need to figure that out,” O’Shanick emphasized.

Fortunately, a few simple questions and exercises can help determine the root cause of the psychiatric symptoms. For example, to determine if agoraphobia symptoms may actually be vestibular in nature, ask your patient if they need to touch the wall to prevent falling when closing their eyes in the shower. Or, if the patients feels anxious in a crowded area like a store or mall, ask if pushing a cart or stroller, or holding on to another person, makes them feel better. If they answer yes, a few simple follow-up tests (eg, the Balance Error Scoring System and Fukuda Stepping Test) can confirm the presence of the medical mimic. Referrals for vestibular physical therapy and a neuro-ENT consultation may prove useful for such patients.

Similarly, to determine if there is social phobia or vergence, ask your patient if they are having trouble seeing or reading books at a normal distance. Then, check their near point of convergence and conduct a cover test. Consider a referral to a neuro-optometrist.

In other cases, a central auditory processing disorder may be confused with attention-deficit/hyperactivity disorder. Ask your patient if they have better sustained attention for visual vs verbal interactions, or if they have trouble understanding what people say if they cannot see their faces or mouths. Weber and Rinne tests can also prove useful, and a referral to an audiologist is indicated.

Posttraumatic neuroendocrine (PTNE) disorders may be relatively common in patients with TBI,3 and mood symptoms are associated with PTNE, O’Shanick explained. Psychiatrists should inquire about changes in menses, sex drive, cold intolerance, and skin and hair dryness to elucidate if PTNE is a potential cause of the mood symptoms. Lab studies should be considered, including free thyroxine, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, immunoglobulin-1, estradiol/testosterone, and AM/PM cortisol. In considering TBI in these cases, O’Shanick reminded attendees that they should not overlook intimate partner violence and child abuse.

Finally, O’Shanick illuminated the inherent biases in the Minnesota Multiphasic Personality Inventory-2 that could lead to incorrect diagnoses. For instance, stomach trouble and headaches score positively on the hypochondriasis scale, but both of these symptos may be related to TBI and TBI treatments. Similarly, positive scores on the hysteria scale result from the patient noting they are unable to work, feel sad, and have trouble sleeping, all of which are associated with TBI.

Ultimately, the psychiatrist is in the ideal position to leverage their medical and behavioral knowledge to support these patients.

“Hopefully, [these insights] will allow you to think a little bit differently when patients come into your office,” O’Shanick concluded. “Maybe ask some increased questions when it comes to injury-related issues, concussion-related issues… to see if there are some other types of medical issues behind some of the anxieties that your patients have. At the end, you may just find that you’re practicing … much more successfully and ultimately helping your patients.”


1. Surveillance report of traumatic brain injury-related emergency department visits, hospitalizations, and deaths. CDC. 2014. Accessed May 2, 2021.

2. Ponsford J, Alway Y, Gould KR. Epidemiology and natural history of psychiatric disorders after TBI. J Neuropsychiatry Clin Neurosci. 2018;30(4):262-270.

3. Beyer C, Zaytsev J, Donegan D, et al. The effects of traumatic brain injury on pituitary function: a systematic review and meta-analysis. J Endocr Soc. 2020;4(Supp 1):SUN-294. ❒

Ketamine: Not a Simple Treatment, but a Worthy One

by Leah Kuntz

"This is not a simple treatment or a treatment to take lightly,” Richard C. Shelton, MD, said during the Q+A portion of the presentation “Ketamine for Depression: Is the Hype Holding Up? Mechanisms and Evidence.” “On the other hand, we’ve seen remarkable results.”

Shelton, director of research of the Huntsville Regional Medical Campus of the University of Alabama, Birmingham (UAB), School of Medicine; the Charles B. Ireland Professor in UAB’s Department of Psychiatry and Behavioral Neurobiology; and director of the UAB Depression and Suicide Center, began with a discussion of ketamine’s functions in the brain. He discussed how it restores the regulatory processes for patients with depression and other mood disorders, using the results of a study by Li et al to illustrate his points.1

“Stressful experiences cause a reduction or retraction of spines and synapses. The brain is less able to control or regulate the emotional state,” Shelton explained.

With ketamine administration, there is an almost immediate increase in formation of critical spine and synaptic proteins.

“When you add ketamine to the system, you produce a rapid return and restoration of those spines and synapses. We see an effect within 24 hours,” Shelton continued. “Ketamine has the ability to restore the regulatory control to the brain and helps, theoretically, to normalize mood.”

Shelton shared data from 8 studies that investigated ketamine; they found ketamine produced a rapid, robust effect for patients with severe treatment-resistant depression.2-9 Data from additional studies demonstrated how ketamine functioned for patients with suicidal ideation.10-13

“The good news: Ketamine really seemed to work in these patients with highly treatment-resistant depression,” Shelton said.

Shelton also addressed key concerns regarding ketamine, especially how it may be a challenge to prescribe. First, the US Food and Drug Administration requires a “somewhat cumbersome” risk evaluation and mitigation strategy program, which requires registration by the clinic, provider, and patient. There are prior authorization hurdles as well as reimbursement issues, he added. Nonetheless, Shelton finds ketamine is more than worth the attendant logistical struggles.

“When I treated my first patient with IV ketamine in 2012, it was just amazing to see the effect occur within 24 hours,” Shelton said.


1. Li N, Liu R-J, Dwyer JM, et al. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry. 2011;69(8):754-761.

2. Berman RM, Narasimhan M, Sanacora G, et al. A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression. Biol Psychiatry. 2000;47(4):332-337.

3. Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856-864.

4. Singh JB, Fedgchin M, Daly EJ, et al. A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. Am J Psychiatry. 2016;173(8):816-826.

5. Daly EJ, Singh JB. Adjunctive intranasal esketamine in treatment-resistant depression—reply. JAMA Psychiatry. 2018;75(6):654-655.

6. Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630.

7. Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428-438.

8. Daly EJ, Trivedi M, Janik A, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019;76(9):893-903.

9. Wajs E, Aluisio L, Holder R, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020;81(3):19m12891.

10. Wilkinson ST, Ballard ED, Bloch MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry. 2018;175(2):150-158.

11. Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Am J Psychiatry. 2018;175(7):620-630.

12. Fu D-J, Ionescu DF, Li X, et al. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent: double-blind, randomized study (ASPIRE I). J Clin Psychiatry. 2020;81(3):19m13191.

13. Ionescu DF, Fu DJ, Qiu X, et al. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: results of a phase 3, double-blind, randomized study (ASPIRE II). Int J Neuropsychopharmacol. 2021;24(1):22-31. ❒

Experts Express Concern Over Excited Delirium Syndrome Diagnosis

by Laurie Martin

There is universal confusion around excited delirium syndrome (ExDS): What is it and how should it be treated? In short, we do not know all the answers, and no comprehensive treatment guidelines or formal criteria exist, according to a panel presentation. Representing the fields of emergency medicine, psychiatry, psychology, and emergency medical service (EMS), the expert panel consisted of Leslie Zun, MD, MBA; Thom Dunn, PhD; Julie Owen, MD, MBA; and Sarah E. Slocum, MD.

Recent events have brought to light the importance of clarifying the differential diagnosis, signs and symptoms, and universal treatment protocols of ExDS, which to date remain unclear.

In the last year, the world witnessed George Floyd dying at the hands of a police officer. In 2019, Elijah McClain, aged 23 years, a massage therapist, was placed in a chokehold by law enforcement and sedated by EMS with 500 mg of ketamine, a tactic that is legal in Colorado to control ExDS. By the time he arrived at the hospital, he was brain dead; he died 3 days later.

How McClain died is a matter of dispute, but 1 thing is clear: These and many, many more incidents in the public eye have shone a spotlight on the use of force by police and in emergency settings.

Dunn, a psychologist who is involved in emergency medical services, shared an ultimately tragic example of ExDS in a hospital setting in which an adult male Black patient demonstrated signs of the condition. The presence of police seemed to intensify the patient’s agitation. He began to sweat profusely, stripped naked, shouted incomprehensibly, and flailed his arms. After multiple attempts to restrain him, police tased him. Emergency staff then administered ketamine, and he subsequently died.

In 2020, the American Psychiatric Association released a position statement on ExDS1:

DSM-5 recognizes Delirium, hyperactive type, but the symptoms of this condition differ in many ways from the symptoms typically attributed to excited delirium (eg, superhuman strength, impervious to pain, etc). Recent data suggest that persons being detained by the police and described as having ‘excited delirium have frequently received medication from emergency medical technicians (EMTs) intended to rapidly sedate them…In some reported cases, it is questionable whether the person identified as having an ‘excited delirium’ actually had any medical condition warranting its use.

The discussion concluded with Slocum’s call for action: “We really need to address this condition as a group and figure out what’s going to be best for that patient.”


1. American Psychiatric Association. Position statement on concerns about use of the term “excited delirium” and appropriate medical management in out-of-hospital contexts. December 2020. Accessed May 22, 2021.

Panel Tackles Ethical Conundrums

by Paul Gleason, PhD

"Ethical dilemmas arise when multiple ethical responsibilities stand in tension with each other,” Charles Dike, MBChB, MPH, told the attendees.

During the discussion, one issue stood out: the possible conflict between psychiatrists’ duties to their individual patients and their duties to promote the good of the public as a whole.

This conflict has become particularly pressing this past year due to the global pandemic, and the panelists considered the problem from several angles as they answered previously submitted questions.

One question concerned confidentiality: What should be done when a patient reports that their parents are sending the patient’s sibling to school, despite the child’s positive SARS-COV-2 virus results?

Daniel J. Anzia, MD, a member of the expert panel, explained, “The participation in public health endeavors is a long-standing, recognized potential exception to the obligation of psychiatrists, and all physicians, to maintain confidentiality.” Past department chair for psychiatry at Advocate Lutheran General Hospital in Park Ridge, Illinois, Anzia said that ideally, the patient—who was no longer a minor—would make the report to the school, and then inform the family that public health officials might be contacting them. But, he added, if the patient refused, “it is permissible for the psychiatrist to make such a report.”

Another questioner asked what psychiatrists should do if patients insisted on being seen in person, even at the height of the pandemic. Panel member Patricia (Tia) Powell, MD, director of the Montefiore Einstein Center for Bioethics in the Bronx, New York, told attendees that they are not required to put themselves at physical risk. “Among our many obligations as psychiatrists is to provide a safe space in which we can offer therapy for our patients. That includes keeping the patient and psychiatrist safe from each other in terms of communicating the virus,” she explained.

In addition, Powell noted that many psychiatrists have extended their knowledge and use of telehealth, discharging their obligation to offer care in person by working with patients to make telehealth possible. If the patient refuses telehealth, protective gear, and vaccination, she said, “it could be legitimate for a psychiatrist to say, ‘At this time, I’m not able to continue working with you.’”

Similarly, are psychiatrists obligated to get an available COVID-19 vaccine? Although “a psychiatrist has a right to refuse the vaccine, the psychiatrist should consider their wider obligations of such a decision, including an unspoken statement—to the psychiatrist’s colleagues and patients—that the psychiatrist does not trust the vaccine,” said Dike, associate professor of psychiatry at Yale School of Medicine and associate program director of its Law and Psychiatry Fellowship. “This could discourage vulnerable patients from taking what could be a life-saving intervention.”

What are the obligations of a psychiatrist to a new patient who has yet to be seen? The panel was presented with a situation in which a new patient reports suicidal thoughts on a previsit questionnaire, and then does not come to the appointment or answer calls. Should the psychiatrist send someone to check on the patient?

Panelist Rebecca Brendel, MD, JD, detected a potential conflict between the psychiatrist’s duty to the individual patient and the public at large. “We’d hate to say we’re not going to screen patients for suicidality because it’s too hard to figure out what to do with the information,” explained Brendel, assistant professor of psychiatry at Harvard Medical School and director of its Master in Bioethics program. However, she noted the need for a follow-up mechanism that does not overstep the bounds of a nascent doctor-patient relationship by violating the prospective patient’s rights to privacy and confidentiality.

One of the more controversial topics over the past few years has been what psychiatrists—or, more broadly, the APA—should say about the national psyche and potentially dangerous political leaders or movements. Brendel quickly reaffirmed the Goldwater Rule, but she also insisted that “psychiatrists can participate in public life by adding insight and knowledge about mental health more generally.” For instance, psychiatrists might use their knowledge of history and psychology to “comment about what might lead groups of persons to become susceptible to certain beliefs, [or] be prone to questioning authority in violent ways. [Psychiatrists can] also…be thinking about how unrest or extremism or discriminatory views might affect certain members of our society, and in particular their mental health.”

The panel reminded attendees that ethics resources and official APA opinions can be found on the APA’s Ethics webpage: Queries can be submitted to the APA’s Ethics Committee staff liaison for further guidance at Alternately, Psychiatric TimesTM readers can submit ethical dilemmas to our Ethics Editor via ❒

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