Paul Gleason, PhD

The Long Shadow of the Towers

Slideshows

Statistical findings from longitudinal studies of mental health among 9/11 witnesses and first responders.


8 Ways to Observe the 20th Anniversary of 9/11

How can we remember those who lost their lives in the 9/11 attacks, and support the mental health of survivors and their families?

8 CMEs You Can Take Today

Our roundup of free CMEs features innovating strategies for diagnosing and addressing the neuropsychiatric signs of multiple sclerosis, the therapeutic potential of psilocybin, poststroke depression, and more. 

Is It a Psychiatric Disorder or a TBI Medical Mimic?

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

 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.

 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,

 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. 

https://www.cdc.gov/traumaticbraininjury/pdf/TBI-Surveillance-Report-FINAL_508.pdf

2. Ponsford J, Alway Y, Gould KR. Epidemiology and natural history of psychiatric disorders after TBI. 

3. Beyer C, Zaytsev J, Donegan D, et al. The effects of traumatic brain injury on pituitary function: a systematic review and meta-analysis. 

Ketamine: Not a Simple Treatment, but a Worthy One

"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 

“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.

 Data from additional studies demonstrated how ketamine functioned for patients with suicidal ideation.

“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.

2. Berman RM, Narasimhan M, Sanacora G, et al. A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression. 

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. 

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. 

5. Daly EJ, Singh JB. Adjunctive intranasal esketamine in treatment-resistant depression—reply. 

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). 

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. 

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. 

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). 

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. 

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. 

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). 

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). 

Experts Express Concern Over Excited Delirium Syndrome Diagnosis

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 

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. 

https://www.psychiatry.org/File%20Library/About-APA/Organization-Documents-Policies/Policies/Position-Use-of-Term-Excited-Delirium.pdf

"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: 

https://www.psychiatry.org/psychiatrists/practice/ethics

. Queries can be submitted to the APA’s Ethics Committee staff liaison for further guidance at apaethics@psych.org. Alternately,

readers can submit ethical dilemmas to our Ethics Editor via 

Articles

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.

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

“Sleep problems are understudied,” Ellen Lee, MD, told attendees at the 2021 American Psychiatric Association (APA) Annual Meeting. “They’re underdiagnosed and undertreated in people with mental illness.” Thus, Lee encouraged clinicians to screen for sleep problems, because sleep “is a modifiable and important target for intervention.” Lee, along with other colleagues, shared insights and preliminary research results on how sleep may impact mental health and psychiatric disorders.

Sleep problems affect between 30 and 80% of individuals with schizophrenia and are associated with lower quality of life and poorer cognitive and frontal lobe functioning, explained Lee, assistant professor in residence in the Department of Psychiatry at the University of California at 

 In as-yet unpublished research, Lee found that sleep apnea is associated with increased inflammation, while higher subjective reports of sleep quality are associated with lower levels of inflammation. Since inflammation is also associated with 

 treating sleep problems could also improve the symptoms of mental illnesses.

Beyond schizophrenia, sleep issues also appear in mood disorders like depression. Stephen Smagula, PhD, presented research on possible links between morning activation deficits and depression among family members caring for patients with dementia.

Older individuals with depression often report difficulty getting up and active in the 

 Morning activation deficits are sometimes thought to be immutable (some individuals are just not morning people), but in functional magnetic resonance imaging readings, dementia caregivers with depression showed higher resting-state amygdala-PCC connectivity, which is associated with stress, fear, and 

 “Although this is speculative,” Smagula cautioned, “it seems plausible that the non-morning type caregivers are doing behaviorally disengaged, emotion-focused coping. So put another way, some caregivers might wake up, feel overwhelmed, say ‘Expletive! I’m going back to bed.’”

This raises the possibility, according to Smagula, who is assistant professor of psychiatry and epidemiology at the University of Pittsburg, that “instead of treating the depression and hoping the morning activation deficit goes away, we could be targeting the morning activation deficit to treat the depression.” Clinicians could consider treatments such as activity scheduling, which would get the caregivers up and moving, increase their light exposure, decrease fragmented sleep, and limit the time they spend ruminating—all of which could improve their depressive symptoms.

Sleep also affects cognition, especially in older adults. Ruth O’Hara, PhD, presented initial data on the impacts of delta activity at sleep onset (DASO). Study participants with DASO demonstrated better affective function overall and over time, which led O’Hara to conclude that testing DASO or other variables may help clinicians predict patients’ cognitive futures. “We think that characterizing sleep dysregulation in older adults may in fact identify valuable biomarkers,” explained O’Hara, who is the Josephine Q. Berry Professor of Psychiatry and Behavioral Sciences at Stanford University. They could “help us predict cognitive decline and onset of dementia, as well as predicting affective dysfunction.”

1. Cohrs S. Sleep disturbances in patients with schizophrenia: impact and effect of antipsychotics. 

2. Keshavan MS, Montrose DM, Miewald JM, Jindal RD. Sleep correlates of cognition in early course psychotic disorders. 

3. Bromundt V, Köster M, Georgiev-Kill A, et al. Sleep-wake cycles and cognitive functioning in schizophrenia. 

4. Lee EE, Ancoli-Israel S, Eyler LT, et al. Sleep disturbances and inflammatory biomarkers in schizophrenia: focus on sex differences. 

5. Smagula SF, Capps CS, Krafty RT. Evaluating the timing of differences in activity related to depression symptoms across adulthood in the United States. 

6. Smagula SF, Karim HT, Ibrahim TS, et al. Resting-state function connectivity associated with being a "morning-type" dementia caregiver and having lower depression symptom severity. 

Sleep problems are understudied, underdiagnosed, and undertreated. 

Dreaming of New Treatments

 has partially clarified the role of microglia cells in the progression of Alzheimer disease (AD), which in turn may lead to new targets for 

Normally, microglia cells are responsible for clearing out amyloid plaques and other kinds of cellular debris, but in cases of AD progression 

 Investigators at Duke-National University of Singapore (NUS) Medical School and Monash University set out to discover why. “We sought to understand the molecular mechanisms and differences between microglia that were actively engulfing amyloid plaques in Alzheimer’s disease and those that weren’t,” Enrico Petretto, PhD, associate professor at Duke-NUS Medical School, said in a statement to the press.

When comparing microglia that were and were not eliminating amyloid plaque, Petretto and his co-investigators found that they had different gene expression patterns induced by the 

 gene. The researchers found that microglia cells with reduced 

 expression also had a decreased ability to take up and eliminate an abnormal protein like amyloid. Conversely, high expressions of 

 were associated with more active and effective microglia cells.

“Understanding this mechanism is important because now we have several new targets to go after, and in the future, these targets may open a new front against this devastating disease,” added Jose M. Polo, PhD, an ARC Future Fellow at Monash University.

 This research is built on a larger Duke-NUS initiative to create a comprehensive map of gene expression changes that are associated with AD 

 and AD remains incompletely understood, “future work could focus on using gene editing tool CRISPR to test the impact of manipulating Hif1a on symptom severity and disease progression,” Gabriel Chow, MD-PhD candidate at Duke-NUS Medical School, further explained.

1. Grubman A, Choo XY, Chew G, et al. Transcriptional signature in microglia associated with Aβ plaque phagocytosis. 

Scientists discover gene signature for plaque-eating microglia in Alzheimer’s disease

Duke-NUS study reveals how individual cell types in the brain contribute to Alzheimer’s disease

. Duke-NUS Medical School. November 28, 2019. Accessed May 27, 2021. 

Gene expressions in microglia cells may explain why some of them are ineffective and allow dementia to progress. 

A New Target for Intervention in Alzheimer Disease? 

“There’s more to trauma than physicality,” Rachel Yehuda, PhD told attendees at the 2021 American Psychiatric Association (APA) Annual Meeting. “For decades we have been talking about how to integrate pharmacotherapy with psychotherapy. But we haven’t understood how to do it.” 

For patients with posttraumatic stress disorder (PTSD), one possibility is combining therapy and mind-altering drugs, like 3,4-methyl​enedioxy​methamphetamine (MDMA), panelists explained.

Mark Bates, PhD, former branch chief for Psychological Health Promotion in the Department of Defense’ Psychological Health Center of Excellence, presented findings from 6 phase 2 trials of combined MDMA and psychotherapy in the 

 The studies included 103 participants who had experienced treatment-resistant PTSD symptoms on average for more than 15 years.

Participants progressed through several types of sessions in all of the studies. First, participants and clinicians conducted an initial, 90-minute interview, preparing the participants for the MDMA-assisted sessions and discussing their PTSD. Then participants underwent 8-hour MDMA-assisted or placebo sessions. During this time, participants wore eyeshades and listened to music, and had the option of discussing their troubling experiences.

The participants who received MDMA experienced an altered mental state, which was believed to make the discussion easier on them as compared with those in the placebo group. “One of the most important features,” Bates said, “is this reduced fear response in combination with increased empathy, trust, and closeness. In the words of one participant, ‘it’s like being in a box full of puppies.’ You can actually feel safe to bring up things that were otherwise very uncomfortable.”

Participants and therapists debriefed for 90 minutes the day after the MDMA session. Integration, Bates explained, helps “the patients retrieve and consolidate much of what happened during the dosing session and integrate it into their daily lives.”

The results of the studies were encouraging, he reported. Among participants who received MDMA, 56% no longer met PTSD criteria by the end of the study and, at a 12-month follow-up, that number rose to 67%.

 Mean change on participants’ Clinician Administered PTSD Scale (CAPS-IV) fell around 45 points. Meanwhile, 23% of participants who received the placebo did not meet criteria for PTSD by the end of the study.

Robert Koffman, MD, dug deeper into the science behind MDMA’s potential effects. “We really don’t know how it is that MDMA actually works,” admitted Koffman, first senior consultant for integrative medicine and behavioral health at the National Intrepid Center of Excellence. He noted research indicates that MDMA seems to create the exact opposite effects of PTSD: Whereas PTSD is associated with increases in amygdalar activity, heightened fear responses, decreased hippocampal activity, emotional numbness and distrustful hypervigilance, MDMA is associated with reduced amygdalar activity, increased hippocampal activity, reductions in fear and defensiveness, and higher feelings of 

 In short, Koffman said, “MDMA increases access to these traumatic memories without the kind of flooding and emotional numbing characterized by the speechless terrors” that usually accompany PTSD.

However, Koffman noted the altered mental state induced by MDMA is not enough to achieve positive results. “What we are really discussing in this talk,” he said, “is the relationship between the drug and the therapy.” In addition, the therapy involves additional training to be successful, he cautioned. A therapist should not try to understand the patients’ problems rationally and then use specific techniques to change their situation; instead, he explained, therapist’ goal should be to mediate their patient’s access to deep states of their psyches and facilitate “a powerful transformational experience of a 

During the Q and A session Yehuda, who is director of the Center for Psychedelic Psychotherapy and Trauma Research at Mount Sinai School of Medicine, said that psychedelic-assisted psychotherapy raised important questions about the nature of psychiatric healing. “This is almost treasonous for a psychiatry meeting,” she admitted, “but the actual molecule and neurochemical effects are probably a lot less important to the healing than the fact that you have provided an opportunity to look at something that [the patient] couldn’t see, because it was either too painful or it was blocked.”

“The future is here,” Koffman concluded. Although MDMA is currently a Schedule 1 drug, the Multidisciplinary Association for Psychedelic Studies “fully expects MDMA to be rescheduled by 2023, possibly even by next year.”

In fact, MDMA treatments are about to pass another important milestone. Next month 

will publish results of a phase 3 trial in which 67% of participants no longer met criteria for PTSD after 2 months of treatment with 

“We are so comfortable with our molecules and our neurochemistry,” said Yehuda. “But I know enough to know that the answers are not just in the molecule. It has to do with the entire healing process. The good news is that makes clinicians really important.”

1. Jerome L, Feduccia AA, Wang JB, et al. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. 

2. Mithoefer MC, Wagner MT, Mithoefer AT, et al. The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. 

3. Feduccia AA, Mithoefer MC. MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? 

Prog Neuropsychopharmacol Biol Psychiatry

4. Mithoefer, MD. A manual for MDMA-assisted psychotherapy in the treatment of posttraumatic stress disorder. Multidisciplinary Association for Psychedelic Studies. August 19, 2015. Accessed May 5, 2021. 

5. Nuwer R. A psychedelic drug passes a big test for PTSD treatment. 

New research find altered states of consciousness may allow veterans and other patients with PTSD to face unspeakable experiences and find peace. 

Looking to the Future of MDMA-Assisted Psychotherapy

Psychiatry may be lagging behind other branches of medicine in an important way.

“In the rest of medicine, as you increase the acuity you increase the number of treatments,” Nolan Williams, MD, told the attendees of the 2021 American Psychiatric Association (APA) Annual Meeting, but in psychiatry, “as we increase acuity we actually lose treatment options.”

Williams and his fellow presenters at a panel on rapidly acting medications

 all had the same question: How can psychiatrists design treatments to respond to sudden-onset conditions?

Williams, assistant professor of psychiatry and behavioral sciences at Stanford University Medical Center, described the situation as “emergency room purgatory.” Because of slow-acting treatments and limited hospital capacity, “the whole process of going through the inpatient unit can take several months,” he said. “The only treatment that we have available for these folks is ECT [electroconvulsive therapy.” But ECT is available in only 10% of US hospitals.

However, psychiatrists might have other options for fast-acting treatments. He shared 

showing that accelerated theta burst repetitive transcranial magnetic stimulation (r-TMS) had positive results for mood disorders, including MDD.

 R-TMS treatment works by stimulating the left dorsolateral prefrontal cortex (DLPFC). In MDD, the DLPFC may be failing to inhibit the subgenual cingulate, and the result of this network failure is cognitive impairment and inwardly directed negative thoughts,” Nolan explained. “By stimulating DLPFC, r-TMS corrects the mood imbalance and restores mood regulation.”

In initial numbers from his study of patients with a treatment-resistant mood disorder (TRD), Nolan found that after 5 days of sessions (10 hourly sessions at 1800 theta-burst pulses per hour), participants improved. On the Montgomery Asberg Depression Rating Scale (MADRS), he found an 80% average reduction of participants MADRS scores.

Another options for fast-acting treatment is ketamine. Charles DeBattista, MD, professor of psychiatry and behavioral sciences at Stanford University, presented evidence for its efficacy for TRD. He noted that ketamine is an anesthetic agent, a μ-opioid agonist, and while its effects on TRD are rapid, making it potentially helpful in psychiatric emergencies. “Often within a couple of hours to a day, patients experience a significant improvement, and the effects were sustained for a week or so,” he said. These effects did decrease after a week, but there is also evidence that repeated injections may lead to 

DeBattista also presented the option of esketamine, which has been fast tracked by the US Food and Drug Administration for treating TRD and acute suicidality in MDD. Multiple studies have found that it rapidly 

New mothers represent another population that might benefit from fast-acting medications. “Maternal mental health is something that’s been an enormous problem forever,” said Samantha Meltzer-Brody, MD, MPH. “Those of us that have the privilege of working with perinatal women are always struck by how debilitating PPD [postpartum depression] can be.” Rapidly acting medications could reduce mortality and morbidity, she said, and allow for more positive interactions between mothers and their newborns.

Although many selective serotonin reuptake inhibitors are approved to treat PPD, she pointed out that their initial effects may not be felt for weeks or even months, and many women’s symptoms do not respond to them. Meltzer-Brody, the Assad Meymandi Distinguished Professor and Chair in the University of North Carolina Department of Psychiatry, also considers an alternative to these medications: neurosteroids like brexanolone.

In a 2018 paper, Meltzer-Brody and her coauthors found brexanolone to be effective for

 Using the HDRS for measurement, the researchers found an average 8- to 10-point reduction in 12 hours, and around an 18-point reduction at 60 hours, the study’s primary endpoint. At day 30, participants average reduction remained, on average, 16 points down from baseline. The paper hypothesized that brexanolone works by increasing γ-aminobutyric acid (GABA) function, which appears to be inhibited during PPD.

With these new options, it seems psychiatry may not lag behind other branches of medicine for long. 

1. Williams N. Developing rapidly acting antidepressants: neurosteroids, dissociative agents (Ketamine Analogues and Psilocybin), and Accelerated Theta Burst r-TMS. Paper presented at: American Psychiatric Association Annual Meeting; May 1-3, 2021; virtual.

2. Nettekoven C, Volz LJ, Kutscha M, et al. Dose-dependent effects of theta burst rTMS on cortical excitability and resting-state connectivity of the human motor system. 

3. Li CT, Chen MH, Juan CH, et al. Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. 

4. Yip AG, George MS, Tendler A, et al. 61% of unmedicated treatment resistant depression patients who did not respond to acute TMS treatment responded after four weeks of twice weekly deep TMS in the Brainsway pivotal trial. 

5. Murrough JW, Perez AM, Pillemer S, et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. 

6. 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. 

7. Fu DJ, 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). 

8. Meltzer-Brody S, Colquhoun H, Riesenberg R, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. 

What treatments could handle both psychiatric emergencies and long-standings mental health conditions—in a hurry?  

Fast-Acting Options for Mood Disorders and Psychiatric Emergencies

“Ethical dilemmas arise when there are multiple ethical responsibilities that stand in tension with each other,” Charles Dike, FRCPsych, MBChB, MPH, told the attendees of the American Psychiatric Association (APA) Annual Meeting.

At a panel on “Ethical Dilemmas in Psychiatric Practice,” one dilemma 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.

One question concerned confidentiality: What should be done when a patient reports her parents are sending another child 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 obligations of psychiatrists, and all physicians, maintaining confidentiality.” Past department chair for psychiatry at Advocate Lutheran General Hospital in Park Ridge, Illinois, Anzia said 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 question asked what psychiatrists should do if patients insisted on being seen in person, even at the height of the pandemic. Panel member, Tia Patricia Powell, MD, Director of the 

, told attendees 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.

Powell noted that many psychiatrists have extended their own knowledge 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, “it could be legitimate for a psychiatrist to say, ‘I’m not at this time able to continue working with you.’”

Along the lines of vaccinations, are psychiatrists obligated to get an available vaccine for SARS-COV-2? 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 

. “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 patient fills in a reports suicidal thoughts on a new pre-visit 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,” said 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 the APA as a whole—should say about the national psyche and potentially dangerous political leaders or movements. Brendel quickly reaffirmed the 

 but 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 “make some comment about what might lead groups of persons to become susceptible to certain beliefs, be prone to questioning authority in violent ways, and also to be thinking about how unrest or extremism or discriminatory views might affect certain members of our society, and in particular their mental health.”

Striking a balance between obligations to patients and society during a plague year might seem like an exceptional circumstance, but Philip Candilis, MD, reminded attendees that medical ethicists have previously faced similar situations. In fact, Candilis, professor of psychiatry and behavioral sciences at George Washington University School of Medicine and Health, noted that the field of medical ethics arguably began during a deadly outbreak. “When Thomas Percival wrote his 

, it was in response to the typhus epidemic in Manchester [UK],” Candilis said. During the plague, doctors fled the city, leaving many patients without care. In response the government demanded new professional guidance and ethical standards for physicians, 

Several decades later, the American Medical Association adopted Percival’s standards. The ethical dilemmas with which he grappled remain relevant today, and they will likely come up again. “How do you protect yourself as a doctor,” asked Candilis, “How do you protect your family, and how do you work for the public good at the same time? This is a difficult, difficult balance to strike.”

The panel reminded attendees that ethics resources and official APA opinions could be find on the APA’s Ethics webpage 

. Queries can be submitted to the APA’s Ethics Committee staff liaison for further guidance at apaethics@psych.org. Similarly, 

 readers can submit ethical dilemmas to our Ethics Editor via 

What’s a psychiatrist to do? An APA ethics panel at the Annual Meeting considered various dilemmas, including possible conflicts between physicians’ obligations to individual patients and their obligation to promote the public good. 

Expert Panel Ponders What It Takes To Be an Ethical Psychiatrist  

has identified a potential new mechanism for treating depression. 

The study, conducted by researchers at the Icahn School of Medicine at Mount Sinai, used the drug ezogabine to open the KCNQ2/3 potassium channels in participants’ brains. The results showed significant improvements in 

 Because anhedonia is associated with poor response to antidepressant medication, worse overall outcomes, and increased suicide risk, this finding is especially important. 

“Our study is the first randomized, placebo-controlled trial to show that a drug affecting this type of ion channel in the brain can improve depression and anhedonia in patients,” said the paper’s lead author, James Murrough, MD, PhD, associate professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai. “Targeting this channel represents a completely different mechanism of action than any currently available antidepressant treatment.”

The study included 45 participants with high levels of anhedonia and divided them into 

 The treatment lasted 5 weeks, with clinical measures of depression and anhedonia taken at weekly visits. Although the study did not meet its primary endpoint at the 5-week mark, it found that participants on ezogabine had increased reward anticipation and large improvements on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Snaith-Hamilton Pleasure Scale (SHAPS), compared with the placebo.

The United States Food and Drug Administration approved ezogabine in 2011 as an anticonvulsant for epilepsy, but this is the first study to test it as a depression treatment. The drug acts on the KCQ2/3 channel, which affects brain cell function by regulating the movement of electrical charges across cell membranes.

A previous study led by co-author Ming-Hu Han, PhD, found that changes in KCNQ2/3 potassium partially determined whether mice showed 

signs of depression and anhedonia following stress

 Mice with increased KCNQ2/3 channels in their brains appeared resistant to depression. When the mice were given drugs to increase KCNQ2/3 channel activity, previously depressed mice no longer showed depressive or anhedonic behaviors.

“The fundamental insight by Dr Han’s group that a drug that essentially mimicked a mechanism of stress resilience in the brain could represent a whole new approach to the treatment of depression was very exciting to us,” said Murrough.

 The previous study by Han’s group paved the way for the current study.

Opening certain potassium channels in the brain reduces depressive symptoms and anhedonia. 