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Existing treatments for posttraumatic stress disorder (PTSD) are few in number and, too often, ineffective. Although still classified as a Schedule I drug, methylenedioxymethamphetamine (MDMA) has improved symptoms PTSD in 

In this Mental Health Minute, Tiago Reis Marques, MD, PhD, shares the results of 

, in which the MDMA-assisted arm of the study outperformed the placebo by 35%. He revisits the history of MDMA and looks to the future, when this Schedule I drug may be approved as a legal treatment.

is a senior clinical fellow on the Faculty of Medicine at Imperial College London, an instructor at the Institute of Psychiatry in King’s College, and the CEO of Pasithea Therapeutics.

Would you prescribe a psychedelic like MDMA? 

Share comments with your colleagues by emailing 

. Comments may be shared online pending review and editing for style.

The latest trial results for MDMA-assisted therapy are in—and they are eye-catching.  

New Hope for PTSD Treatment?

Psychodynamic psychotherapy has receded into the background in many residency programs. But according to Richard D. Lane, MD, PhD, psychotherapy is not only foundational to the history of psychiatry—it still has a lot to offer.

In this Mental Health Minute, Lane uses a brain-based perspective to reimagine how psychotherapy works. In his latest book, 

Neuroscience of Enduring Change: Implications for Psychotherapy

, he collects the latest neuroscientific research on how psychotherapy works and translates the scientific findings into ideas for effective clinical practice.

is Professor of Psychiatry, Psychology, and Neuroscience at the University of Arizona.

How should neuroscience inform psychiatric practice? 

Key neural mechanisms are responsible for emotion, memory consolidation, and lasting personal change. 

What Are the Neuroscientific Secrets to Successful Psychotherapy?

“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

Motherhood depicted in film is replete with meaning, symbolic to the core.

17 Films About the Horrors of Motherhood

The poem “No Sympathy for Other” is inscribed on the face of the United Nations Building. The words were written by the Persian poet Saadi more than 800 years ago:

The sons of Adam are limbs of each other,

Having been created of one essence.
When the calamity of time affects one limb

The other limbs cannot remain at rest.
If thou hast no sympathy for the troubles of others
Thou art unworthy to be called by the name of a human.

We are interconnected. The worldwide COVID-19 pandemic has made that crystal clear.

The same is true for the worldwide crisis posed by climate change. Each crisis dramatically reveals the preexisting fractures in our society. Communities of color are first and most profoundly impacted by both COVID-19 and climate change and are least able to 

 The roots that link climate change and COVID-19 are neither inherent to the virus, nor to the dynamics of global warming. The profound disparities are driven by social determinants and the socioeconomic and political structures embedded in our society.

As early as the mid-1970s, scientists began warning the world community about threats of climate change. Most of their predictions fell on deaf ears. Yet their predictions have been remarkably accurate. What the scientists did not accurately predict was just how quickly we would be facing the consequences. The impacts are not in faraway places, nor in the distant future. No longer can we turn a blind eye as the fury and frequency of climate-driven disasters intrude on our lives.

We are forced to face multiple crises simultaneously: the pandemic, climate change, and the effects of racism. The worldwide COVID-19 pandemic has triggered a massive international health crisis and fueled economic decline, in which escalating poverty and disparities of wealth are inescapable. Rightful rage about centuries of simmering structural racism has ignited a movement demanding urgent racial justice.

Nightly news broadcasts reporting on the daily death toll of COVID-19 keep us attuned to the presence of the pandemic. Since the climate disasters occur more episodically and are spread across different locales, it is all too easy to let concerns recede into the background. How much can we face at one time? Nonetheless, we cannot afford to ignore the climate crisis; physics and Mother Nature will not wait. We ignore this at our own peril.

Structural racism refers to the laws and regulations, the resulting systems, and the cultural practices and norms that result in differential access to 

resources, opportunities, power, and wealth

 These are core sociopolitical issues that are embedded in American history and current society. The legacy of inadequately addressed racism has created the current intolerable disparities in our society, including marked disparities in health outcomes for communities of color. These structural components combine with the climate crisis to exacerbate the differential impacts that climate-driven events and disasters have on poor individuals and communities of color. Climate events act as threat multipliers, adding to and exacerbating current dangers.

Although we Americans are not unique in our capacity for racism, our history is built on genocide, slavery, colonialism, and the annihilation of what, in psychoanalytic language, is often called “the other.” Founded on principles of the Doctrine of Discovery and Manifest Destiny, European settlers saw the New World through 

 They hardly questioned the belief that what was here was for their taking. Progress was to exploit the land, expropriate the homeland from native occupants, and to extract the most out of African slave labor. Marching through time also meant the annexation and colonization of Brown communities. Later in 20th century, our foreign policy was dictated by securing alliances and controlling puppet governments for access to greater wealth and power. Examples abound in our efforts to control emerging countries in Central America and Southeast Asia.

Although the accumulation of wealth has been the preeminent economic driver of American imperialism, there are profound connections between psychic mechanisms and industrial capitalist growth. Enabling this quest for wealth, deeply embedded unconscious intra-psychic processes have allowed us to hold at arms’ length the historical suffering inflicted by genocide, slavery, and colonialism. These are the very same mechanisms in play when it comes to ignoring the destruction and aggression inflicted today on the communities that are most dramatically impacted by climate disruption.

Additionally, these same unconscious processes underpin our attitudes and our relationship with the natural world; destruction and aggressive plundering of our environment are all too common. We are left with damaged, scared, soiled places all the while feeling nostalgically perplexed about what has happened. What has gone wrong? How did the natural world, which previously brought solace and psychic restoration, begin to bring pain and mourning for the past? Note the new concept of 

, describing that deep melancholic grief when experiencing the change to our natural environment, 

Psychoanalyst Melanie Klein describes primitive paranoid-schizoid states that shed light the intra-psychic mechanisms operative in this realm.

 Only the “I” exists, and “the Other,” the mother, only exists as an extension of the desires and needs of the voracious infantilized self. Since there is no “other,” we are unable to experience other humans as brothers and sisters.

This infantile state also allows us to view the earth as nothing other than an inexhaustible source of supplies that exist for our pleasures. This has allowed us to take from Mother Earth endlessly and deny any limits on consumption.

Just as we have plundered the earth with willful disregard for the consequences, we have discounted the suffering of those who are most affected by climate ravages. Primarily, psychic defenses must minimize the suffering of people of color and keep our minds in a detached, distorted, intellectualized sphere. The false belief that African Americans do not experience pain in the same way that Whites do is an example of 

 To retain our emotional comfort requires us to unconsciously experience “the other” in 2 dimensional and dehumanized ways, or worse, as nonexistent in our minds.

We are also faced with a modern psychological epidemic within 

 Just as hysteria was the dominant psychic disorder during Freud’s time, we are now facing a modern epidemic of narcissism: a preoccupation with the individual or the self.

Narcissistic qualities are efforts to manage underlying, often unconscious feelings of inadequacy, inferiority, and insecurity. Such fragile states are managed through an inflated sense of superiority, self-aggrandizement, and a sense of entitled attitudes and behaviors. This requires undervaluing others to sustain the delicately inflated sense of self, often resulting in disregard for others and 

Such narcissistic qualities in individuals can be extended to broader manifestations seen in our socioeconomic-political groups. Isabella Wilkenson, the first woman of African-American heritage to win the Pulitzer Prize in journalism, builds on ideas of narcissism as she reframes the issues of racism through the lens of a 

 As on the fixed rungs of a ladder, each knows his specified place in the caste hierarchy. For example, the decades of socioeconomic losses of the white underclass and working classes have threatened their previously more stable place in the caste hierarchy. Struggling with the greater economic disparities and insecurity have threatened whole communities. Reacting against mounting pressure for justice from communities of color, some white communities collectively manage these threats with the compensatory sense of superiority and entitlement. In the effort to keep out the pain that would come with loss of status, the downtrodden find solace in collective grandiose fantasy. Desperate attempts to restore the threatened equilibrium have unleashed the current white supremacy movement, along with its violence.

Psychoanalyst Donna Orange, PhD, PsyD, has linked racism and climate change with unconscious 

 She describes these processes as states of “exaggerated entitlement,” reflecting attitudes of cultural superiority. The psychic states of denial and disavowal (knowing facts about climate change but experiencing the self as buffered from impacts) are dependent on this irrational sense of specialness and superiority which, she argues, is rooted in centuries of colonialism and slavery. Orange elaborates that we have been “morally numbed,” which contributes to our failure to deal with the climate crisis in general, and specifically the impacts of climate on communities of color.

The retreat to regressive psychic states in face of fears is not only ineffective in creating needed social solutions, but it also comes at great costs. Relying on fragile, unstable psychic structures cuts us off from the full range of feelings. Emerging from paranoid-schizoid position and narcissistic states allows for greater, more nuanced capacities to tolerate real limits, experience our common-ness, and recognize our dependency and interconnections with others and the natural world.

I suggest that we are all too vulnerable to regressive states when confronted by the magnitude and repeated assaults of climate disasters, and we must use our more mature selves to face the dual impacts of structural racism and climate chaos. It is tough to see, feel, and hold sympathy for the troubles of others. But as Saadi’s poem reminds us, we are “created as one essence,” and our “limbs cannot remain at rest” when others are in pain.

I reside in the traditional territory of the Ramaytush-Ohlone-Muwekma Nations and honor the ancestral community that inhabited and cared for this land. It is this dedication and awareness that inspired me to lead this series.

This collection of articles will highlight the specific ways various communities of color have been uniquely impacted by climate disruption. While the specific stories may be idiosyncratic, the shared interconnections cannot be lost. The final article will address some shared solutions.

We must rise to the challenge Saadi issued in his poem centuries ago, when he challenged us to be worthy “to be called by the name of a human.”

is clinical associate professor in the Department of Psychiatry at the University of California, San Francisco.

The impacts of climate change on human health in the United States: a scientific assessment

. US Global Change Research Program. April 4, 2016. Accessed April 15, 2021. 

2. Bailey ZD, Feldman JM, Bassett MT. How structural racism works - racist policies as a root cause of US racial health inequities. 

An Indigenous Peoples’ History of the United States for Young People

4. Albrecht G, Sartore GM, Connor L, et al. Solastalgia: the distress caused by environmental change. 

Introduction to the Work of Melanie Klein

6. Hoffman KM, Trawalter S, Axt JR, Oliver MN. Racial bias in pain assessment and treatment recommendations, and false beliefs about biological differences between blacks and whites

Narcissism: the science behind the rise of a modern ‘epidemic.’

. March 11, 2016. Accessed April 15, 2021. 

New insights into narcissistic personality disorder

. February 29, 2016. Accessed April 15, 2021. 

10. Orange DM. Climate and Justice. Lecture presented at the San Francisco Center for Psychoanalysis. April 1, 2019.

Climate Crisis, Psychoanalysis, and Radical Ethics

. Routledge, Taylor & Francis Group; 2017.

Powerful psychic defenses are keeping humanity from facing a number of interconnected crises. How can these psychic defenses be overcome? 

Introducing a New Series: Racism and Climate Change 

In 2020, I had the honor of receiving The Sigourney Award, a great distinction, but also a great responsibility.

Allow me to tell you a bit about myself. 

 is my profession and my passion. I began my journey to become a psychoanalyst during my university studies. I attended the Universidad Autónoma Metropolitana in Mexico, then obtained a master’s degree in psychoanalytic theory. I decided to continue my education in France, where I received another master’s degree in psychoanalysis at the Sorbonne University. Later, I completed my PhD at the École des Hautes Eestudes en Sciences Sociales de Paris. I had the honor of studying with Jacques Derrida, Gilles Deleuze, and Élisabeth Roudinesco, and completed my hospital training at La Borde Clinic with Félix Guatarri and Jean Oury. In France, I continued my personal analysis that I had started in Mexico; however, psychoanalysis, for me, cannot remain only in university studies and private practices.

I returned to my country and faced a difficult reality. Mexico is a beautiful country, inhabited by many cultures, and a mosaic of regional languages ​​and diverse histories. But it is also rife with violence. Mexico is one of the countries with the most femicides in the world. Between 2007 and 2016, approximately 22,482 women were murdered in Mexico, according to the National Institute of Statistics and Geography (INEGI). Every 4 hours, the violent death of a girl, young woman, or adult woman occurred. The violent death causes included mutilation, suffocation, drowning, hanging, cut throats, burning, stabbing, or shooting.

 In 2018, the UN found that 6 out of 10 Mexican women have faced an incident of 

. Furthermore, 41.3% of women have been victims of sexual violence and, in its most extreme form, 9 women are murdered every day.

I was born, raised, and developed professionally in Mexico, and I feel this pain keenly. I have 2 daughters: Emi, a Latin Americanist; and Luci, a dancer. I also have a son, Bruno, a poet. My existence was conceived in Latin America. My wife, partner, and colleague, Marcela Martinelli, PhD, came into exile from Argentina for state violence as a child.

In the 1970s, many dissatisfied Latin American citizens suffered the weight of state-supported violence and repression, with quite a few going into exile. One of the most injured countries was Argentina, where the exile involved around 2 million citizens. Between 1908 and 1976, there were 300 concentration camps in Argentina and 30,000 were “disappeared.”

In Mexico, it is estimated that from 1964 to today, 79,000 people have “disappeared.”

What is happening in Mexico and Latin America makes me want to investigate what psychoanalysis could say about cruelty, violence against girls and women, and the painful dimension of trauma in order to breakdown the violence.

In response to this violence, I have created 3 movements with other psychoanalysts. My colleagues and I currently maintain the School of the Psychoanalytic Letter and the Social Trust of Psychoanalysis. The School is a space for study, discussion, and writing, where we ponder the 

 of psychoanalysts. We hold conferences, organize meetings, write books, submit to magazines, and hold international meets for those who want to become psychoanalysts.

In the Social Trust, we try to open clinical spaces so that female victims of violence and relatives of the disappeared can have a space for a psychoanalytic listening. We have designed what we call psychoanalytic listening clinics where psychoanalysts with rigorous training receive low-income patients in addition to the population of the aforementioned groups. Today, we have 2 clinics, 1 in Oaxaca and another in Cuernavaca. Soon we will open others in Puebla and Morelia. The dream is to open clinics throughout Mexico.

The listening clinics are established through the following procedure: first, there is a presentation to the community through an inauguration ceremony and the distribution of flyers in the neighborhood. Then, agreements are made with nongovernmental organizations, human rights groups, feminist groups, and government agencies. Finally, the clinics start to receive patients. The School of Psychoanalytic Letter works on training young psychoanalysts to staff these clinics. In addition to individual sessions and singular supervisions, clinical conferences and case presentations are held every week.


The implementation of these clinics has taught me that psychoanalysis has to be included in city life and society. It is necessary to make citizens aware of the existence of these places and services where they can receive help addressing their pain, and to ensure that psychoanalysts understand the importance of their clinical work with citizens experiencing violence.

is a psychoanalyst and cofounder of the School of the Psychoanalytic Letter and the Social Trust of Psychoanalysis.

1. Muedano M. Imparable, el crimen contra las mujeres; cifras del Inegi. 

http://www.excelsior.com.mx/nacional/2017/10/22/1196308

2. World Health Organization. Violence against women. March 9, 2021. Accessed March 11, 2021. 

http://www.who.int/mediacentre/factsheets/fs239/es/

3. Calveiro P. La experiencia concentracionaria. In: Lidia CE, Crespo H, Yankelevich P, eds. Argentina, 1976. 

4. Gomez A. Nearly 79,000 people have disappeared in Mexico since 2006. 

https://aldianews.com/articles/culture/nearly-79000-people-have-disappeared-mexico-2006/61501

Mental health care for victims of violence may be a way out of the darkness for Latin America.  

Psychoanalysis as a Tool Against Violence

In the United States, psychoanalysis has typically been a treatment for the wealthy upper-class. But according to Patricia Gherovici, PhD, this is not the case in her native Argentina, where “everybody does it—rich and poor.”

In this Mental Health Minute, Gherovici reveals the surprising political history of psychoanalysis in Argentina and tells the story of her efforts to bring psychoanalysis to the disenfranchised in the US.

is a psychoanalyst, analytic supervisor, and recipient of the 2020 Sigourney Award. She is associate faculty for the psychoanalytic studies minor at the University of Pennsylvania (PSYS). She is the author of 6 books, most recently 

Psychoanalysis in the Barrios: Race, Class, and the Unconscious

 (with Chris Christian). It received the Gradiva Award for best edited collection and the American Board and Academy of Psychoanalysis Book Prize in 2021. 

See previous coverage of the Sigourney Awards in 

How can psychoanalysts and psychiatrists better serve marginalized communities? 

A psychoanalyst shares her experience working with patients whose lives are marked by poverty, migration, and race and gender discrimination.  

Latinx Psychoanalysis

During the last year of my residency in psychiatry, I watched a TV series called 

, a comedy-drama series that played for 6 years. Main character Joel Fleischman was a neurotic physician from New York City who had just completed his residency in family medicine. Joel had agreed to work for 4 years in Alaska in exchange for the state financing his medical education. He was assigned to work in the remote fictional village of Cicely, which had a lively and eccentric population.

One of my favorite scenes, which I can still vividly recall, was a conversation between Joel and Leonard, the local Inuit shaman. Leonard shares with Joel his wonder at the ways of modern medicine. He cannot understand how Joel can spend only 15 to 20 minutes with a patient and be able to construct a diagnosis and treatment plan from that brief encounter. Leonard explains to Joel that for him to diagnose and treat a patient he needs to live with that individual for several days to see what their stressors are, watch them while they sleep, understand their lifestyle and interpersonal interactions, and observe their diet patterns and exercise activity.

At that time, in 1990, insurance companies allowed us to meet with our patients for 1-hour visits each week. The first 10 minutes was usually focused on medication management, and the remaining 40 minutes were spent engaging in various types of psychotherapy. After my residency I practiced this style for a few years at a local community mental health center. Despite the weekly 50-minute appointments it often took me 6 to 12 months to begin to understand the complexities and biographical significances of each patient. I treated a man who presented with a classic major depressive disorder. He was a successful local businessman who rarely missed his weekly 50-minute appointment. It was only after meeting for 12 months that he started to discuss his chronic and disabling obsessive compulsive symptoms. He felt shame and embarrassment when he first began to share his dark secrets, but ultimately had a great response to treatment.

It was in the early 1990s that the ensuing 

 intruded into the medical profession, patients had to get authorization for their initial psychiatric evaluation and for 1 or 2 follow-up visits. I would then have to fill out a treatment plan form and request authorization for 3 or 4 more visits. After several years of this nuisance, the insurance plans determined they were spending more money to manage treatment authorizations than they were saving by managing us, so this protocol was discontinued.

The next step was a classic move-countermove battle of wits. Insurance companies decreased payments to psychiatrists for a 50-minute visit, because the insurance companies were of the opinion that lengthy visits could be provided by other professions who could be paid significantly less. As a result, psychiatric visits shrank to 30 minutes; payment for two 30-minute visits was significantly more than one 50-minute visit. The insurance companies executed their next countermove by lowering the payment amount for a 30-minute visit. A counter-countermove by some psychiatrists was to then see 3 patients per hour, allowing the billing for 3 units of treatment instead of 2. Alas, the response was a predictable counter-counter-countermove that ultimately led to the current general structure for psychiatrists to see patients for a so-called “

Leonard the shaman would be extremely impressed or, more likely, appropriately deeply saddened by how little time psychiatric providers in most clinics now spend with patients. I would like to propose a new model: the 16-minute medication check.

Think of all the additional information we could learn about or convey to our patients if we used that extra minute to simply ask 1 or more of these questions:

1. Tell me about the most important individuals in your life.

2. What is it like for you in your work environment?

3. Do you have any questions about any of the medications that I am prescribing for you?

4. Have you considered a trial to lower one of your medication’s dosage?

5. Could you remind me of your active medical problems?

6. What are your long-term goals in life?

7. Who lives with you, and how do you get along?

9. What is a typical breakfast, lunch, and dinner for you?

10. Do you feel rested when you wake up in the morning?

11. Who do you feel had the greatest influence on you growing up?

14. Do you exercise regularly? If so, what type and how often?

15. Would you like me to review the common and rare side effects of your medications?

16. What is the one bad habit you would like to change?

17. When do you feel most at peace with yourself?

18. Do you feel safe in your home and your neighborhood?

19. How do you feel your treatment here is going?

20. Do you have any questions about your diagnosis(es)?

A final reflection: if you were meeting with a psychiatrist for a 

, how would you feel if you were asked any of these questions? Just asking! ❒

 is medical director, Brain Health, Exeter, NH; editor in chief, 

; staff psychiatrist, Seacoast Mental Health Center, Exeter, NH; consulting psychiatrist, Exeter Hospital, Exeter, NH; consulting psychiatrist, Insight Meditation Society, Barre, MA.

If we had 1 extra minute with our patients, what question would we ask?

The 16-Minute Med Check

“An uplifting experience” is how a prominent Southern California aesthetic medicine specialist described to me the reaction from a notable number of his patients having botulinum toxin treatments during the 

 (COVID-19) pandemic. Multiple needle sticks in their face notwithstanding, these patients took particular relish in cocooning themselves (however briefly) in a 

 of self-indulgence, effectively sequestered from the barrage of unique stressors now understood to be associated with COVID-19.

This isolated anecdote may be simple serendipity or an example of a potential intervention. A recently published article might stimulate discussion about the potential of broadly effective management with neurotoxin injections.

 used the FDA Adverse Event Reporting System (FAERS) to analyze more than 40,000 botulinum toxin treatment reports across a variety of medical and cosmetic indications including hyperhidrosis, facial rhytides, migraine prophylaxis, spasticity, and spasms. They reported a significantly lower number of depression reports across all indications and injection sites compared with patients undergoing alternative treatments for the same conditions.

They also found a significantly lower incidence of depression-related adverse events (AE) with neurotoxin treatment compared with the control groups. For example, reporting odds ratios (ROR) of botulinum toxin’s depression AE frequencies were uniformly significantly lower compared with control, ranging from 0.12 (95% CI: 0.04, 0.33) to 0.60 (95% CI: 0.48, 0.74), irrespective of indication. The ROR analysis necessitates that 

k associated with neurotoxin use has a reasonable underlying pharmacodynamic hypothesis. Therefore, these findings should be considered cautiously, as they may not reflect actual number of cases or frequencies in the general population as the FAERS system is voluntary and open to the public.

Although botulinum toxin does not have regulatory approval for the treatment of depression in the United States, this information should offer food for thought that there is a possibility that neurotoxin treatment may show promise in mitigating depressive symptoms. In fact, numerous reports corroborate the efficacy of botulinum toxin in attenuating symptoms related to major depressive disorder,

 including several randomized placebo-controlled trials and observational studies.

 Some believe that the muscles involved in facial expression, such as the corrugator muscles that elicit frowning, play a pivotal role in modulating the brain’s emotional circuitry and neural activity.14-17 Put simply, it is postulated that expressive behavior can alter emotional states, likely through afferent sensory modulation.

Botulinum toxin injections have an excellent safety profile. 

 reported no significant differences in the overall incidence of AEs, including serious AEs, in almost 2000 patients treated with botulinum toxin compared with patients treated with placebo injections based on the pooled results of 9 trials. Specifically, in trials of major depression, corrugator and procerus neurotoxin injections have noted that treatment-emergent AEs were localized to the treatment site and were temporary (headache and injection site irritation).

 That said, it will remain critical to evaluate the comparative effectiveness of neurotoxin treatment versus established psychopharmacological options and psychotherapeutic strategies and determine if and where it might fit into the current treatment paradigm.

One of the barriers is training mental health professionals on how to perform freehand injections, particularly those that require dose accuracy at multiple injection sites as with neurotoxin injections. Even with extensive experience, injection dose accuracy is difficult to achieve. 

 recently calculated that the average accuracy error associated with freehand injection of 40 consecutive 0.025 mL doses from a 1.0 cc syringe was approximately 10% for 2 highly-experienced injectors. Recognizing the urgency to achieve dose accuracy, several neurotoxin-dedicated devices have been developed and are undergoing clinical and regulatory evaluation.

In conclusion, preliminary evidence suggests botulinum toxin may have a positive impact on depressive symptoms. Additional research needs to be conducted to better determine the safety and efficacy of this treatment. If the data indicate this may be a worthwhile treatment option, administration barriers also will need to be addressed

is an independent clinical trialist and medical device consultant in San Francisco, CA. Website: 

. The author reports no conflicts of interest concerning the subject matter of this article.

1. Salari N, Hosseinian-Far A, Jalali R, et al. Prevalence of stress, anxiety, depression among the general population during the COVID-19 pandemic: a systematic review and meta-analysis. 

2. Ettman CK, Abdalla SM, Cohen GH, et al. Prevalence of Depression Symptoms in US Adults Before and During the COVID-19 Pandemic. 

Postmarketing safety surveillance data reveals antidepressant effects of botulinum toxin across various indications and injection sites

4. Alam M, Barrett KC, Hodapp RM, Arndt KA. Botulinum toxin and the facial feedback hypothesis: can looking better make you feel happier? 

5. Finzi E. Update: Botulinum Toxin for Depression: More Than Skin Deep. 

6. Parsaik AK, Mascarenhas SS, Hashmi A, et al. Role of Botulinum Toxin in Depression. 

OnabotulinumtoxinA for the treatment of major depressive disorder: a phase 2 randomized, double-blind, placebo-controlled trial in adult females

8. Chugh S, Chhabria A, Jung S, et al. Botulinum Toxin as a Treatment for Depression in a Real-world Setting. 

9. Finzi E, Rosenthal NE. Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial. 

10. Magid M, Finzi E, Kruger TH, et al. Treating depression with botulinum toxin: a pooled analysis of randomized controlled trials. 

11. Magid M, Reichenberg JS, Poth PE, et al. Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study. 

12. Wollmer MA, de Boer C, Kalak N, et al. Facing depression with botulinum toxin: a randomized controlled trial. 

13. Zamanian A, Ghanbari Jolfaei A, Mehran G, Azizian Z. Efficacy of Botox versus Placebo for Treatment of Patients with Major Depression. Iran J Public Health. 2017;46(7):982-984.

14. Franca K, Lotti T. Botulinum toxin for the treatment of depression. 

15. Hennenlotter A, Dresel C, Castrop F, et al. The link between facial feedback and neural activity within central circuitries of emotion--new insights from botulinum toxin-induced denervation of frown muscles. 

Although botulinum toxin does not have regulatory approval for the treatment of depression in the United States, some reports indicate neurotoxin treatment may mitigate symptoms.

Psychotherapy