 is an award-winning psychiatrist who has specialized in the cultural and ethical aspects of psychiatry. A prolific writer and speaker, he received the one-time designation of Hero of Public Psychiatry from the Assembly of the American Psychiatric Association in 2002. To create a better world, he is an advocate for treating mental health issues related to climate instability, burnout, Islamophobia, and anti-Semitism. He serves on the Editorial Board of

Yesterday was the second annual Major League Baseball Field of Dreams game. It takes place in Iowa, near the site of the popular 1989 movie titled “Field of Dreams.”

Going Into the Woods with Child Psychiatry

The Positive Psychiatry Baseball Hug of Sportsmanship Seen Around the World

I watched the first game. I recall that I cried trice, once when Kevin Costner led players from both teams from the towering cornstalks onto the field and at the end when my beloved Chicago White Sox won with a walk-off home run.

I had once dreamed of playing for the White Sox and have something like that come true. When I had a compound fraction of my left ankle skiing in my senior year of high school, my dream turned to psychiatry and addressing the dreams of patients.

The movie itself time travels over baseball history and a father son relationship. To summarize, Ray Kinsella, played by Costner, facing financial ruin, hears a voice saying:

He then razes a cornfield and builds the baseball diamond. In some sort of vision, the field draws in real life legendary baseball players who missed out on their dream. That stimulates Ray to look into his own regrets. As the last player is ready to leave after resolving their regrets, Ray recognizes that it is his father as a young, happy man. Ray then hears the field whispering “ease his pain,” and realizes that refers to his own Oedipal-like guilt about his torn relationship with his father. Ray asks his father to play catch and forgives him. In life imitating art, the former well-known Black father-son baseball duo, Ken Griffey Sr. and Jr. played catch before this year’s real game started yesterday.

The United States of America, has traditionally been founded and thought to have been a field of dreams, at least when it is open to immigrants, as the famous 1903 poem by Emma Lazarus inside the Statue of Liberty states:

Your huddled masses yearning to breathe free . . .”

My 18-year-old paternal grandfather was one of them, escaping conscription into the Romanian army in 1898. Apparently, the rest of his family died in the Holocaust. On the other hand, much earlier in our country’s history, the forcible nightmarish bringing of Africans here to be slaves occurred. Intergenerational transmission of trauma may still need more resolution on both sides, former immigrants and slaves.

The voices and visions that Ray has are not like that of a psychotic depression, but maybe more like a psychiatrist making key interpretations. We can see here that a simple game of baseball can have much deeper meanings, just like in working with a patient.

I, too, had some similar conflicts with my father, who often played catch with me and took me to White Sox games when I was a child. Seeing the movie and then the first Field of Dreams game brought tears of relief, as if I had hit a relationship saving home run of life.

is an award-winning psychiatrist who has specialized in the cultural and ethical aspects of psychiatry. A prolific writer and speaker, he received the one-time designation of Hero of Public Psychiatry from the Assembly of the American Psychiatric Association in 2002. He is an advocate for mental health issues related to climate instability, burnout, Islamophobia, and anti-Semitism for a better world. He serves on the Editorial Board of

Articles

America and Psychiatry as Fields of Dreams

has been writing a poem about his experience of being a doctor every month for the past 24 years in

in a column called “Poetry of the Times.” He is instructor in psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts. His latest book is

Videos

"...I would take you and take you and take you deep into any kind of nest you ever wanted."


The Hummingbird: A Seduction

is an outpatient psychiatrist at Prisma Health-Upstate and clinical associate professor at the University of South Carolina School of Medicine, Greenville. He served on the American Psychiatric Association’s Task Force to Address Structural Racism Throughout Psychiatry, and he currently serves as the Diversity and Inclusion section editor and advisory board member for

 fosters innovative perspectives on peace via the arts. By looking to artists from various disciplines (eg, painting, sculpting, music, photography, and poetry), the festival hopes to cross cultural boundaries and cultivate open dialogues, healing, and reconciliation. With his impressive work in the arts and healing, this year 

Diversity and Inclusion Editor, will be a featured speaker.

We invited Dr Clark to share his thoughts on the festival, and how the arts and psychiatry can and should work closely with one another.

: How has the arts helped you to find peace and healing? How do you leverage the arts in your clinical practice to promote understanding and resiliency?

: The arts provide a perpetual sense of inward renewal and transformation for my mind, body, and soul. We all seek to find balance and improve self-regulation throughout our lives. Writing poetry has allowed me to strive toward these goals.

I first started writing poetry when I was medical school and used poetry to transcend living with clinical depression and cope with the arduous journey of medical school. It remains a cathartic antidote for me. It also has helped me become more vulnerable in regard to sharing my work with a wider audience.

I encourage my colleagues and my patients to tap into their creative side. We are multi-dimensional beings who must embrace our authenticity as we seek to find meaning and purpose in our lives. The arts serve as the mouthpiece that unites humanity and fosters humility.

: This will be my first time attending the International Peace Festival. I had a providential connection on LinkedIn several months ago with Angelique Codina, the Executive Vice-President of International Peace Festival. I was intrigued by her profile given her affinity for the arts. I figured I had nothing to lose by reaching out to a kindred spirit with shared interests.

We stayed connected on the LinkedIn platform, and I asked if should knew anyone in the music scene who would be interested in performing several of my poems that had been set to music. After the South Carolina Philharmonic 

 by composer Dick Goodwin, DMA, in February 2022, I have been determined to share my work on a global stage. I received positive feedback from Angelique after she listened to the performance. Months later, much to my surprise, she invited me to be a keynote speaker for the festival.

I am most looking forward to the experience of being at festival that promotes peace and healing through multiple forms of art. I believe it will be a gratifying experience to be in a space that fosters transformation, reconciliation, and love.

: Can you tell us a bit about your talk at the festival as well as some of the other speakers?

: I consider it an honor and a blessing to be one of the featured speakers. I will be a part of a panel highlighting the intersectionality between music and medicine specifically focuses on mental health. I plan to talk about my service on the South Carolina Philharmonic board of directors and the creation of the 

, which has had a positive impact on patients and their families in our state. I will also talk about how I utilize poetry and music as a psychiatrist to help illuminate several topics in our society, including trauma, Black mental health, diversity, equity, and inclusion (DEI), and burnout.

The executive team has put together a diverse group of speakers which include, poets, journalists, musicians, composers, and chief executive officers who are have a shared interest in promoting harmony within humanity.

I recently had the opportunity to join a Zoom call with 2 of the speakers, Clifton Joseph and Kostantinos Matzaleris. In addition to this experience, we have begun brainstorming further ways we can collaborate in the future. They are both change agents who have done remarkable things throughout their careers. (You can read more about them at 

https://internationalpeacefestival.com/speakers

.)I am looking forward to their hearing about their experiences and invaluable contributions to help their communities flourish.

: Your commitment to social justice is impressive. Have you always been drawn to issues of “bettering the world?” Do you think it is a common trait among psychiatrists?

: I am of the belief that we are created to serve as vessels of change and light in our communities. Each of us has a gift that can be used to make the world a better place. I believe God has blessed me with the gift of creativity. When I implement this gift, I believe it glorifies Him and blesses others.

Poetry is my way of seeing, hearing, and advocating for humanity. I believe psychiatrists are committed to promoting humanity which beckons social justice.

The festival takes place September 21 – 25, 2022, in Toronto. Readers interested in attending the festival can learn more at 

Psychiatric Times Diversity and Inclusion Editor shares insights on the arts, humanity, and peace.

Psychiatrist Featured at Upcoming Peace Festival

There has been a recent revolution in the development of digital health solutions for various chronic conditions. However, there are relatively few examples of digital health solutions that have been widely adopted in real-world health care settings and are measurably improving patient outcomes or helping health care systems deliver efficient and patient-centric care. From our vantage, there are some fundamental reasons for this “translational gap,” which, if addressed, can go a long way in helping realize the full potential of digital health technologies.

We use mental health/illness as an exemplar because brain-related illnesses will be at the forefront of digital health revolution, as their course can be monitored, outcomes can be measured via digital phenotyping, and interventions can be delivered digitally and remotely. Furthermore, the challenges and opportunities in digital mental health have been further highlighted by the ongoing COVID-19 pandemic, which has added fuel to an already brewing mental health crisis.

Mental Illnesses: The Need and the Opportunity

Mental illnesses represent some of the most prevalent and disabling conditions. Depressive disorders ranked number 4 in age group 10-24 and number 6 in age group 25-49 in the list of leading global causes of level 3 disability-adjusted life-years (DALYS)

 and are associated with a wide range of negative outcomes, including loss of occupational function,

 A key barrier to addressing these challenges stems from inadequate metrics to assess disease status, treatment effectiveness, and patient-relevant outcomes.

Mental illnesses do not have a clear outcome measure such as HbA1C in diabetes; instead, efficacy and outcome measures utilized in clinical practice today are complex and subjective, and are only sporadically collected or recorded in databases. As a result, assessment of quality of mental health care often defaults to the more easily measured process and structure metrics, which are distal from true patient outcomes, and, although they are easier to measure, improvement in these metrics does not always translate to improvement in patient-centric outcomes.

 This hampers outcome-relevant assessment of quality, which in turns hampers creation of value-based incentive structures that would lead to true patient-centric care and direct resources based toward the most impactful interventions (“pay for performance”).

The relative value of patient-generated digital data in driving measurement- and outcome-based care will be disproportionately high in mental health since brain-based disorders manifest with changes in behavior, cognition, and mood that are ripe for digital phenotyping. For example, recent and ongoing digital phenotyping efforts in patients with depression are demonstrating correlations between symptom severity and smartphone and wearable-derived features relevant to daily functioning such as physical activity and sleep as measured by actigraphy,

 sociability as measured by blue-tooth handshakes,

 and anxiety or stress as detected in speech features (natural language processing, or NLP) or physiological read-outs such as Galvanic Skin Response (GSR) and Heart Rate/Heart Rate Variability (HR/HRV). Such digital readouts can be more sensitive to real-time measures of symptom severity, functional impairment, and recovery status than episodic clinical assessments. These digital measures may also serve as proxy measures to assess value and efficacy of clinical care and interventions.

Of course, payers and clinicians will require that evidence for this be generated through long-term digital phenotyping studies that relate digital biomarkers with clinical milestones and cost. This will require long-term adherence to digital phenotyping solutions from the ultimate data source: the patient. Adoption and adherence have been challenges

 that can only be addressed if, regardless of the eventual utility for clinicians and payers, digital phenotyping solutions treat the patient as their first and foremost customer.

Using Patient-Generated Data and Digital Tech for Patient-Centric Care

Utilizing digital health technologies and patient-generated data for enabling outcome-based care hinges on developing a “data partnership” with the patient that is built on principles of trust, mutual benefit, and informed data access and use. This will become more urgent as advances in wearable technology and mobile health provide patients greater control over, access to, and use of their personalized health data. In fact, eventually the boundary between health care data primarily housed in electronic health records (EHRs) and so-called patient-generated health data will blur as agency shifts to the patient and we realize that all data—whether in EHRs or generated by wearable devices—is ultimately patient-generated, and thus, is patient owned and controlled.

Matters of privacy, transparent consenting, and, more broadly, trust are clearly “table stakes” for patient participation in a digital data collection regime. Beyond that, in our experience, conducting long-term multimodal digital phenotyping studies in patients with mental illnesses, 3 factors are most important for patient acceptance, engagement, and long-term adherence. First, any sustained digital phenotyping data collection, in the context of research studies or clinical care, must provide immediate “here and now” value and utility back to the patient, over the friction and burden it creates. This equation can be helped by relying on passive data collection and developing bandwidth-frugal applications with minimal impact on smartphone battery life and other factors important to patients.

Furthermore, the end-user interface and visualizations must be engaging and useful to patients.

 Designing such a solution requires a systematic data-driven understanding of patients’ attitudes, motivations, and barriers toward data collection.

 It is important to follow the common tech industry practice of co-designing solutions in close partnership with end-customers (patients), with iterative learn and improve cycles. We may find ourselves surprised at how often the end-users’/patients’ views on which features are important to them diverge from experts’ preconceived notions.

Second, altruism remains a significant motivator; most patients diagnosed with a serious condition are willing—even eager—for their data to be utilized in research that helps their fellow patients, assuming privacy and security safeguards. This propensity to be part of citizen-science efforts should be leveraged to develop “learning engines” wherein pooled, deidentified digital phenotyping data can be used to solve important problems of broad utility and impact.

Finally, we see physicians’ use of patient-generated data to improve clinical care as crucial motivator for patients to adhere to a digital data regime. In fact, this is perhaps the single most important criterion for patients with serious mental illness who are under the care of a clinician. From the physician’s perspective, the data and visualizations should make the clinic visit more efficient and should integrate readily with their current workflows. Such a system will also improve outcomes by improving patient engagement and enabling more measurement-based care,

 We believe digital health solutions that enhance the patient-physician interface and generate near-term value for both may require more effort for initial uptake, but are most likely to stick than direct-to-patient approaches often utilized by insurance companies and digital health solution providers.

While physicians’ awareness of patient-derived digital data and overall digital platforms was already on the upswing prior to COVID, the pandemic has provided further tailwinds for such solutions.

 The initial deployment of digital phenotyping in clinical care settings will necessarily rely on validated self-reported scales of symptoms, function, and quality of life such as the disease set recommendations by the International Consortium for Health Outcomes and Measurement (ICHOM)

 to implement simple, interpretable flags and known treatment algorithms to aid clinical decision making.

Eventually, growing datasets will enable validation of digital biomarkers and predictive algorithms that are leading indicators of disease burden, health care utilization, crises, relapses, and other cost-driving events that could provide payers with real-time, leading quality metrics that can duly reward risk reduction and preemption. The 

 summarizes the framework of a “learning engine”

 digital health solution that we think can be deployed in mental health to bring together patient-derived digital data and clinical data from EHRs to deliver value to all key stakeholders: patients, physicians, and payers.

Digital Health Solution Framework for Filling the Measurement Gap to Enable Outcome-Based Care in Mental Health

The previously described digital phenotyping framework could become an extension of existing EHRs and clinical decision-enabling software systems, but given the already noted challenges in integrating patient-generated health data (PGHD) into EMRs,

 we expect earlier evolution of stand-alone digital phenotyping solutions that are interoperable with multiple EMR systems.

Collection of longitudinal digital phenotyping data at scale in the real world would necessarily imply reliance on data from patient-owned consumer devices. This will require a concerted effort to develop platform-independent data standards and APIs that can ensure that digital biomarker readouts across different devices are comparable.

Increasingly, data will be analyzed and appropriate features extracted in-situ on the device, which will ease privacy concerns and reduce bandwidth requirements, both of which can severely limit scalability and deployment. We should also note that digital phenotyping solutions that collect continuous data for asynchronous use during patient-physician interaction are distinct from—and in fact, complementary to and synergistic with—synchronous telemedicine solutions that enhance physician reach and accessibility.

In addition to lack of actionable patient-generated outcomes data, true patient-centric and value-based care in mental health is also hindered due to fissures between mental and physical care (ie, a lack of a “whole person” approach). For instance, there is mounting evidence that patients suffering from mental health conditions have markedly poorer outcomes while incurring significantly higher direct medical costs for their physical comorbidities.

 However, such comorbid depression is often undiagnosed or otherwise poorly treated, if at all. Remote assessments and digital diagnostics now offer new scalable ways to detect depression and anxiety and set individuals on a path to formal diagnosis. Digital health solutions can also provide evidence-based tools for self-monitoring, self-care, and management of depression, anxiety, and stress for patients with a primary physical health diagnosis.

Furthermore, comorbid patients can be provided access to high-quality behavioral health care virtually. The virtual behavioral health team can work in partnership with primary/secondary providers treating their chronic physical comorbidities. In this context, use of physician-supervised or autonomous digital therapeutics can also be considered to further address behavioral health co-morbidities in a scalable and effective manner.

The COVID-19 pandemic has illustrated the value of digital technology in health care and has created significant momentum that should be leveraged. Although significant advances have been made, we believe digital solutions can play an even greater role in transforming care. This is particularly true in mental health, where there are inadequate objective measures of disease status or progression. These gaps hinder effective measurement-based patient care as well as an opportunity to better align incentives and scarce resources through more meaningful outcomes-based care. We believe an appropriately designed and safeguarded digital health solution can be used to improve patient care and, at the same time, begin to address critical data gaps needed to enable patient-centric, value-based care.

head of strategy and innovation, Davos Alzheimer’s Collaborative. 

 is the founder and CEO of Holmusk Technologies Inc. 

 is chairman of the board at TheSteinberg Institute. 

 is lead of the Brain Capital Alliance, co-lead of the OECD Neuroscience-inspired Policy Initiative in collaboration with the PRODEO Institute, and senior fellow for Brain Capital with the Meadows Mental Health Policy Institute. 

 is director of the San Bernardino County Department of Behavioral Health. 

 is visiting professor, Oxford University and Duke University, and previously global therapeutic head of neuroscience for Janssen Research & Development, LLC.

 Dr Insel is an advisor to Alto Neuroscience, Cerebral, Compass Pathways, Koa Health, and Valera Health. Drs Narayan and Manji are employees of Jansen Research & Development, LLC, and may hold company stock.

1. GBD 2019 Diseases and Injuries Collaborators. 

Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

 [published correction appears in Lancet. 2020 Nov 14;396(10262):1562]. 

2. Cambridge OR, Knight MJ, Mills N, Baune BT. 

The clinical relationship between cognitive impairment and psychosocial functioning in major depressive disorder: a systematic review

3. Saragoussi D, Christensen MC, Hammer-Helmich L, et al. 

Long-term follow-up on health-related quality of life in major depressive disorder: a 2-year European cohort study

A reassessment of the relationship between depression and all-cause mortality in 3,604,005 participants from 293 studies

5. Kilbourne AM, Beck K, Spaeth-Rublee B, et al. 

Measuring and improving the quality of mental health care: a global perspective

Relationship between major depression symptom severity and sleep collected using a wristband wearable device: multicenter longitudinal observational study

7. Vesel C, Rashidisabet H, Zulueta J, et al. 

Effects of mood and aging on keystroke dynamics metadata and their diurnal patterns in a large open-science sample: a BiAffect iOS study

8. Laiou P, Kaliukhovich DA, Folarin AA, et al. 

The association between home stay and symptom severity in major depressive disorder: preliminary findings from a multicenter observational study using geolocation data from smartphones

Predicting depressive symptom severity through individuals' nearby Bluetooth device count data collected by mobile phones: preliminary longitudinal study

10. 25% of users abandon apps after one use. Upland Software, Inc. Accessed July 20, 2022. 

https://uplandsoftware.com/localytics/resources/blog/21-percent-of-users-abandon-apps-after-one-use/

11. Simblett S, Matcham F, Curtis H, et al. 

Patients' measurement priorities for remote measurement technologies to aid chronic health conditions: qualitative analysis

12. Richardson S, Sinha A, Vahia I, et al. 

13. Simblett S, Greer B, Matcham F, et al. 

Barriers to and facilitators of engagement with remote measurement technology for managing health: systematic review and content analysis of findings

14. Hickie IB, Davenport TA, Burns JM, et al. 

Project Synergy: co-designing technology-enabled solutions for Australian mental health services reform

15. Hong RH, Murphy JK, Michalak EE, et al. 

Implementing measurement-based care for depression: practical solutions for psychiatrists and primary care physicians

Transforming population-based depression care: a quality improvement initiative using remote, centralized care management

17. Andrews JA, Craven MP, Jamnadas-Khoda J, et al. 

Health care professionals' views on using remote measurement technology in managing central nervous system disorders: qualitative interview study

18. Depression & anxiety. ICHOM Connect. Accessed July 20, 2022. 

https://connect.ichom.org/patient-centered-outcome-measures/depression-anxiety/

Moving from 'diagnose and treat' to 'predict and pre-empt' in neuropsychiatric disorders

20. Cresswell K, McKinstry B, Wolters M, et al. 

Five key strategic priorities of integrating patient generated health data into United Kingdom electronic health records

21. Davenport S, Gray TJ, Melek S. How do individuals with behavioral health conditions contribute to physical and total healthcare spending? Milliman, Inc. August 13, 2020. Accessed July 20, 2022. 

https://www.milliman.com/-/media/milliman/pdfs/articles/milliman-high-cost-patient-study-2020.ashx

Considering challenges and opportunities in digital health solutions for mental health care.

Digital Health as an Enabler for Patient-Centric, Outcome-Based Care

“Too many people are suffering, and this [psychedelic] mental health revolution is so overdue,” said Reid Robison, MD. As depression continues to plague many patients, psychedelic medicine may offer a new option to clinicians and patients. Here, Robison shares his journey in discovering the promise and potential of psychedelics, and how it might hold the answer to addressing mental health care issues.

is a board-certified psychiatrist and chief clinical officer at Numinus. He has been working with ketamine in research and clinical settings for more than 12 years. He is currently principal investigator of a number of psychedelic studies, including ones looking at psilocybin and LSD. Robison previously served as a coordinating investigator for the MAPS-sponsored MDMA-assisted psychotherapy study of eating disorders.

We have an urgent need for new and improved treatment options for depression—are psychedelic medications the answer?

The Potential of Psychedelics

I was attending a lecture on movement disorders approximately 4 years ago when the speaker, a neurologist, described how, in neurology, the term 

 (EPS) is an example of a “4-letter word.” Yes, one of those irreverent and foul 4-letter words that have most of their letters replaced by “*”s. The neurologist went on to say that a psychiatric referral to a neurologist requesting evaluation for EPS is like a neurologist referring us a patient for evaluation for a psychiatric disorder. 

It was refreshing to hear this, as I have always viewed the adverse event term EPS, which includes many potential movement disorder adverse effects from antipsychotics, to be far too vague and nondescript. 

 lists the numerous movement disorders that are defined as an EPS adverse event during clinical trials submitted to the US Food and Drug Administration (FDA).

Movement Disorders Included Under "EPS" as an Adverse Event in FDA Trials of Antipsychotic Medication

Additionally, since the FDA approval of 2 vesicular monoamine transporter type 2 (VMAT2) inhibitors (deutetrabenazine and valbenazine) in 2017 for the treatment of tardive dyskinesia (TD), the new standard is to describe the various medications that can cause TD and other types of EPS by the mechanism by which these movement disorders are putatively caused: dopamine-2 receptor blocking agents (D2RBAs). 

Although all antipsychotics do block the dopamine-2 (D-2) receptor, drugs in other classes also block this same receptor and have the same risks of causing EPS. A few common examples include metoclopramide, which is used for the treatment of gastroesophageal reflux disorder and diabetic gastroparesis, and prochlorperazine, which is commonly prescribed to treat nausea and vomiting.

The first description of EPS in medicine occurred in 1952 when drug-induced parkinsonism was seen in patients treated with our very first antipsychotic medication, chlorpromazine.

 Five years later, the first case report of TD was published, which occurred in a patient who was also being treated with chlorpromazine. As the antipsychotic mechanism of chlorpromazine was ultimately believed to be related to its ability to block the D-2 receptor, 2 additional types of EPS were added to the list: acute dystonic reactions and akathisia. 

These 4 movement disorders are common adverse events from all D2RBAs, and as we have increased our understanding of the neuropathophysiology of these 4 movement disorders, we now understand them as distinct from each other both in terms of etiology and treatment. 

 provides a simple overview of the different properties of these 4 types of movement disorders as well as the different treatments for them.

Four Most Common Types of EPS From Antipsychotics

Significantly, the presentation and treatment of these movement disorders are quite heterogenous. Acute dystonias and drug-induced parkinsonism are believed to result from a dopamine-acetylcholine imbalance that results from the blockade of the D-2 receptors. This results in a disequilibrium, creating a relative excess of acetylcholine activity due to the relative decrease in dopamine activity resulting from the D-2 receptor blockade. 

An acute dystonia, such as an oculogyric crisis or torticollis, can be quite frightening to the patient, as the dystonia occurs rapidly and can be painful. Fortunately, the treatment is simple and results in immediate relief. Administering the patient an anticholinergic drug (including diphenhydramine, benztropine, or trihexyphenidyl) appears to restore the dopamine-acetylcholine balance. Treatment is usually only required for a few days or a week at most.

Drug-induced parkinsonism follows a different clinical path, although it is quite variable in both time of onset and duration. The same 3 anticholinergic drugs are used to treat drug-induced parkinsonism; however, the treatment is longer and can last for weeks to months. The ultimate goal is to taper off the anticholinergic medication as soon as possible to minimize the many burdensome adverse events of anticholinergic medications (eg, blurred vision, dry mouth, tachycardia, urinary retention, constipation, cognitive impairment, effects on thermoregulation). Alternatively, amantadine can be used, which has a different—albeit not fully understood—mechanism of action.

Akathisia sits in a category by itself, as there are many etiologies to it in addition to D-2 receptor blockade. One common example is selective serotonin reuptake inhibitor–induced akathisia. Not surprisingly, anticholinergics often do not improve akathisia. Like drug-induced parkinsonism, there is also a large range of variability in both time of onset and duration. 

The first step, if possible, is to lower the dose of the D2RBA or change to a different one. Beta-blockers have proved to be the most effective pharmacological treatment, with most of the published literature supporting propranolol. Second-line treatment, in the appropriate patient, is clonazepam. Some evidence suggests that mirtazapine may also be of benefit.

Tardive dyskinesia emerges over time, often not appearing for years or even decades. If the D2RBA dose is decreased, TD will initially look worse due to withdrawal dyskinesia, which will last from 4 to 8 weeks after lowering the D2RBAs dose. For approximately 80% of patients, some degree of TD will be irreversible. It is well established that anticholinergic medications increase the risk of TD and should be avoided in patients with TD. 

The 2 VMAT2 inhibitors described earlier are both quite effective, and the evidence to date suggests that discontinuation of the VMAT2 inhibitors results in recurrence of the TD symptoms. The recently updated American Psychiatric Association guidelines for the treatment of schizophrenia serve as an excellent reference for the diagnosis and treatment of these 4 movement disorders.

We have come a long way in understanding the relationship between D2RBAs and movement disorders. In addition to the 4 movement disorders reviewed here, Table 1 puts in perspective the immense diversity of potential movement disorders that can emerge from the use of D2RBAs. The diagnosis and treatment for each of these can vary significantly, and treating one can worsen another. So to continue to improve our diagnosis and treatment of the numerous movement disorders that can occur with the use of D2RBA, I would like to ask that 

is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief, 

; Staff Psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Exeter Hospital, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

Extrapyramidal side effects: a historical perspective

2. Pringsheim T, Gardner D, Addington D, et al. 

The assessment and treatment of antipsychotic-induced akathisia

The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia, Third Edition

. American Psychiatric Association; 2021. ❒

Is the term, "extrapyramidal symptoms," an example of a “4-letter word”?

Everyone Please Stop (EPS)

To date, there are only 2 medications that have US Food and Drug Administration (FDA) approval for the acute treatment of major depressive disorder in children and adolescents: fluoxetine (ages 8 to 17 years) and escitalopram (ages 12 to 17 years). Placebo response rates in the 50% range have contributed to negative findings in double-blind placebo-controlled antidepressant trials for the treatment of 

 in youth. Further evidence-based antidepressant treatments are needed for children and adolescents with depression. Recent studies provide new information about treatment for depression in youth.

There have been 2 prior randomized double-blind placebo-controlled trials that evaluated the efficacy of duloxetine in the treatment of major depression in children and adolescents.

 Fluoxetine was the active control in these studies. Duloxetine was not statistically different from placebo on change from baseline to endpoint on the Children’s Depression Ratings Scale-Revised (CDRS-R) total score. Similarly, fluoxetine did not statistically differ from placebo. These studies were considered to be inconclusive since neither duloxetine nor fluoxetine separated from placebo on the primary outcome measure.

To further evaluate the efficacy and safety of duloxetine, Saito et al conducted a 6-week randomized double-blind placebo-controlled trial for treatment of children and adolescents with major depressive disorder in Japan.

 In this trial, 149 youth aged 9 to 17 years were randomized to duloxetine or placebo. All participants received 4 video sessions of 

Duloxetine final doses were either 40 or 60 mg/day. There was no significant difference on CDRS-R total score from baseline to endpoint between the duloxetine group and placebo group. Response rates (> 50% improvement on CDRS-R) were similar between duloxetine (32.4%) and placebo (32.4%) groups. The most common treatment-emergent adverse events for duloxetine were nausea, somnolence, decrease appetite, and nasopharyngitis.

The efficacy and safety of vortioxetine was assessed in adolescents (aged 12 to 17 years) with major depressive disorder.

 To minimize placebo response, this study used a 4-week single-blind lead-in period during which adolescents received a standard 3 session Brief Psychosocial Intervention (BPI) plus placebo. To reduce expectation bias, participants and their families were blinded to the time of the randomization. After the 4-week lead-in period, those patients who did not respond to treatment were randomized to 8 weeks of continued BPI plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg (active control), or placebo.

In the lead-in, 784 patients were enrolled and 616 were randomized to 1 of the 4 treatments. The primary outcome measure was change in CDRS-R total score from randomization to week 8. The average effect of the 2 doses of vortioxetine was compared to placebo, and there was no significant difference between vortioxetine and placebo on the primary outcome measure. There was a statistically significant difference between fluoxetine and placebo on the primary endpoint. Response rates (≥ 50% change from randomization in CDRS-R total score) were 42% for vortioxetine 10 mg, 43% for vortioxetine 20 mg, 50% for fluoxetine, and 36% for the placebo groups. Importantly, the placebo response rate in this study was lower than the typical 50% range for other antidepressant trials in adolescents. This may be attributable to the single-blind lead-in and blinding for participants and families as to the timing of randomization employed in this study design. Of note, 13% (103 of 777 patients) of participants responded to treatment during the single-blind treatment phase. Treatment-emergent adverse events with an incidence of 5% or more for vortioxetine treatment were nausea, headache, vomiting, nasopharyngitis, diarrhea, and dizziness.

Antipsychotics are used to treat depression in children and adolescents who have not responded to prior treatment with an antidepressant. To date, there are no controlled trials of combination 

 and antidepressants to treat major depression in youth. Jeon et al examined whether there were neurological adverse events with the adjuvant use of antipsychotics with antidepressants in children and adolescents with depression.

 Their aim was to determine the risks of adjuvant use with antipsychotics compared to antidepressant only use in children with depression.

This retrospective cohort study used the Health Insurance Review and Assessment claims database criteria in Korea. Children and adolescents aged 2 to 18 years with depression who began treatment with antidepressants between 2010 and 2018 were included in the study population. The incidence of movement disorders (Parkinsonism, dystonia, extrapyramidal symptoms, chorea, and tics) and seizures were assessed in 4 time-varying exposures with antidepressant-only use, antipsychotic-only use, concomitant use, and no use.

The final cohort included 9890 children and adolescents. The risk of movement disorders increased during the period of concomitant use (adjusted hazard ratio [aHR], 3.68) and antipsychotic-only use (aHR, 3.84) compared with antidepressant-only use. Similarly, the risk for seizures increased during the period of concomitant use (aHR, 2.06) and antipsychotic-only use (aHR, 2.05) compared to antidepressant-only use. For both cohorts, the antipsychotic dose in the concomitant use was lower than the dose in the antipsychotic-only use group. Higher dose of antipsychotics was associated with an increased risk of movement disorders (low dose: aHR, 3.28; high dose: aHR, 5.38). Similarly, increasing the daily dose of antipsychotics was associated with an increased risk of seizure development (low dose: aHR, 1.91; high dose: aHR, 2.30).

During the period of concomitant use of antipsychotic and antidepressants, the risk of movement disorder was highest with haloperidol, followed by polypharmacy, aripiprazole, risperidone, and quetiapine. Risk of seizure was highest with polypharmacy, followed by 

, aripiprazole, and risperidone. These results suggests that the potential development of movement disorders and seizure should be carefully considered with the use of adjunctive antipsychotics for the treatment of depression in children and adolescents.

Although not commercially available in the United States, agomelatine efficacy and safety were evaluated for the treatment of children and adolescents with major depressive disorder receiving psychosocial counseling in 9 countries.

 After a 3-week run-in period, 400 children and adolescents (aged 7 to 17 years) who were unresponsive to psychosocial therapy were randomized to agomelatine (10 mg/day or 25 mg/day), active control (fluoxetine 10 to 20 mg), or placebo for a 12-week trial. Standardized manualized psychosocial counseling was continued throughout the double-blind randomized controlled trial. At week 12, agomelatine 25 mg/day was statistically significant from placebo on the primary outcome measure of change in the CDRS-R a total score from baseline. Similarly, fluoxetine was significantly superior to placebo. Although statistically significant, Cohen’s effect size for agomelatine 25mg/day was small (0.29) and similar to fluoxetine (0.26).

The most frequent adverse events with agomelatine were thirst, dry mouth, and weight increase. Agomelatine has been associated with the potential to increase liver enzyme concentrations in the blood. The incidence of reversible aminotransferase increases more than 3 times the upper limit of normal was 1% in both agomelatine groups, 2% in fluoxetine group, and 0% in the placebo group in this trial.

In a case series, the effectiveness of a single esketamine administration either subcutaneous (SC) or intravenous (IV) on reducing depressive symptoms and 

 for adolescents with major depressive disorder and suicidal ideation was examined (Faria-Guimaraes et al 2022).

 Eight patients received 0.5 mg/kg esketamine SC, and 2 patients received 0.5 mg/kg esketamine IV.

A significant decrease in depressive symptoms (mean total Montgomery-Asberg Depression Rating Scale score) and suicidal ideation was found from baseline to 24-hour postadministration. The most frequently reported adverse events were dissociation (50%), dizziness (40%), and drowsiness (30%). There was no treatment-emergent suicidality. Although the results are promising, large-scale controlled trials are necessary to further assess the efficacy of esketamine for treatment of depression and suicidality in adolescents with major depression.

In addition to antidepressant medication, 

 (ECT) is an option for treatment resistant depression. To date, there are no controlled trials of ECT for the treatment of children and adolescents with major depression. A recent systematic review examined the effectiveness and adverse-event profile of ECT for treatment-resistant mood disorders in children and adolescents.

 The review included 41 studies (20 case series, 2 case-controlled studies, and 19 case reports). Out of 601 patients, 322 were diagnosed with unipolar depressive disorder. Patients received an average of 12 ECT treatments.

Most studies used the Clinical Global Impression Scale as a measure of improvement and reported response rates for depression ranging from 53% to 77%. For those studies that used objective depression symptom ratings scales, treatment improvement averaged 64%. For those studies with n > 30, response rates for depression were 70 to 82%. The Mini-Mental State Exam was used in 7 studies, and there was no evidence of significant posttreatment cognitive impairment. However, subjective reports of cognitive symptoms were common, particularly short-term memory complaints. Other common adverse effects reported were headache, nausea, vomiting, confusion, agitation, and muscle soreness. Treatment-emergent mania and prolonged seizures were reported in some cases. Discontinuation due to adverse effects occurred in 1.5% of cases.

Based on this review, the investigators suggest that ECT is safe and effective for the treatment of mood disorders in child and adolescent populations and should be considered in severe and treatment-refractory cases. The investigators acknowledge the limitation of the data since most of the literature was case series. Further investigation of the efficacy of ECT for treatment-resistant mood disorders in children and adolescents is needed.

is professor and chair of the Department of Psychiatry and Behavioral Sciences at the University of Texas Medical Branch in Galveston, Texas.

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A double-blind efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder.

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Vortioxetine for major depressive disorder in adolescents: 12- week randomized, placebo-controlled, fluoxetine-referenced, fixed-dose study.

 Association of treatment with antipsychotics, antidepressants, or both with movement disorders and seizures among children and adolescents with depression in Korea.

Further evidence-based antidepressant treatments are needed for children and adolescents with depression.