Mar 9, 2020 | Psychiatry
Dr. Murrough recently launched a TRD Program, featuring esketamine as a treatment option. He is a leader in clinical research in this area, such as the ongoing multi-center clinical trial known as ELEKT-D, which compares the safety and effectiveness of ketamine vs. electroconvulsive therapy.
In March 2019, intranasal esketamine—a form of ketamine marketed as SPRAVATO™ CIII Nasal Spray*—was approved by the U.S. Food and Drug Administration (FDA) to treat patients with treatment-resistant depression (TRD). James Murrough, MD, PhD, Director of Mount Sinai’s Depression and Anxiety Center for Discovery and Treatment, was deeply involved in the research that led to esketamine’s FDA approval. In November 2019, he launched a TRD Program at the Icahn School of Medicine at Mount Sinai, featuring esketamine as a treatment option. Below, Dr. Murrough breaks down the top five things to know about esketamine based on his experience over the past decade.
1. What it is. Esketamine is a potent variant of the drug ketamine, which has been used for 50 years in medical settings as an FDA-approved anesthetic. Ketamine is used off-label to treat depression, typically via intravenous infusion; esketamine, on the other hand, is administered at registered centers via nasal spray and is now FDA-approved for the treatment of TRD in conjunction with an oral antidepressant. It is classified as a controlled substance, and is not available for use outside of approved treatment centers. Prescription of esketamine is restricted through a specialized FDA-regulated program designed to minimize potential risks associated with a medication, known as a Risk Evaluation and Mitigation Strategy (REMS) program.
2. How it works. Via a series of complex biological processes, esketamine enhances the activity of glutamate in brain regions that are important for mood. (Glutamate is the principal neurotransmitter that excites cells in the brain and throughout the central nervous system.) This alteration in glutamate signaling is thought to increase neuroplasticity to 1) allow the brain to cope more effectively with stress, and 2) reverse depression-related brain changes. Because impaired neuroplasticity is linked to depression, the patient’s symptoms improve as the neuroplasticity increases, enhancing resiliency and enabling the patient to create new, more positive thoughts and behaviors.
3. How it’s administered. Esketamine takes five to ten minutes to administer via nasal spray, but patients remain under supervision for two hours for monitoring and are unable to drive for the rest of the day. The antidepressant effects may occur within days in some patients, in contrast to other antidepressants that typically require at least four to six weeks for effectiveness. As stated in the esketamine prescribing information, the treatment course begins with an acute induction phase that involves administering the nasal spray two times a week for four weeks. The first dose of this induction phase is 56 mg; however, the dose may be increased to 84 mg at subsequent visits depending on the patient’s reaction. If the patient exhibits evidence of the therapeutic benefit at the end of induction phase, the patient enters the maintenance phase of treatment. For this phase, dosing frequency should be decided on a case-by-case basis to determine the least frequent amount that still maintains clinical improvement.
4. Side effects. The most common side effects of esketamine are dissociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk. Additional data is being collected on an ongoing basis, and will likely uncover insights about potential longer-term side effects associated with continuous treatment.
5. The evidence. Years of research beginning in the late 1990s culminated in esketamine being developed and then approved in 2019 as the first mechanistically novel, non-monoaminergic antidepressant for patients with TRD. Early academic studies showed that even single doses of intravenous ketamine led to rapid and robust antidepressant effects in patients with TRD, with short-term responses rates generally between 60 and 70 percent. Subsequently, FDA registration trials testing the antidepressant effects of esketamine in TRD were comprised of three short-term trials, one randomized withdrawal trial, and one open-label longer-term safety study. FDA approval was granted based on two positive efficacy studies (one short-term and the randomized withdrawal trial), together with an acceptable safety profile. Meta-analytic studies using all available data confirm that treatment with esketamine leads to a significant beneficial effect in patients with TRD.
Dr. Murrough an Associate Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai. He is currently a site investigator on the ongoing multi-center clinical trial known as ELEKT-D, which compares the safety and effectiveness of ketamine vs. electroconvulsive therapy. He is actively involved in clinical research aimed at discovering safe, effective antidepressants with novel mechanisms of action.
*Mount Sinai was involved in the research that led to the development of this new treatment method for treatment-resistant depression and receives financial remuneration from the manufacturer of SPRAVATO. Mount Sinai’s Dean is a co-inventor of patents related to this new treatment method and as such receives remuneration through Mount Sinai from the manufacturer. For more information about these financial interests and Mount Sinai’s leadership role in SPRAVATO, please visit bit.ly/esketamine-development. (Dr. Murrough does not have a financial interest in SPRAVATO.)
Updated on Jun 30, 2022 | Psychiatry
Sabina Lim, MD, MPH, Vice President and Chief of Strategy for Behavioral Health at Mount Sinai Health System, and Joan Bell, LCSW, Clinical Director of The Mount Sinai Hospital’s Psychiatry Ambulatory Services. Photo by Richard Vernon.
On Saturdays during the month of February, a group of organizations that support the homeless known as the Rescue Alliance, including Salvation Army, The Bowery Mission, Hope For New York, and New York City Relief, host an annual service event called Don’t Walk By. Volunteers canvass the streets and subway lines of Manhattan to introduce themselves to those in need, and invite them to dinner at a host site where they are offered a hot meal, a backpack filled with supplies for the winter (socks, blanket, etc.), basic medical care, psychological support, behavioral health referrals, connections to support services, and a safe and warm place to unwind. In 2019 and 2020, clinicians from across the Mount Sinai Health System have participated by providing brief counseling, crisis intervention, and coordination of care to mental health and addiction services.
On February 1, Hillary Perlman, LCSW, Manager of the Mount Sinai Morningside Psychiatric Mobile Crisis Team, Kay Hua, MD, a psychiatry resident at Mount Sinai Morningside and Mount Sinai West, and Laura Diamond, LMHC, EdM, MA, Counseling Supervisor for the inpatient detox/rehab program at Mount Sinai West, provided mental health counseling and opioid/substance use counseling and referrals in downtown Manhattan. The volunteers helped individuals identify which services they wanted to utilize while they were at the event and advocated for them throughout the process. They also distributed naloxone kits to those interested and provided instructions on how to use them.
Hillary Perlman, LCSW, Manager of the Mount Sinai Morningside Psychiatric Mobile Crisis Team, Kay Hua, MD, a psychiatry resident at Mount Sinai Morningside and Mount Sinai West, and Laura Diamond, LMHC, EdM, MA, Counseling Supervisor for the inpatient detox/rehab program at Mount Sinai West. Photo by Richard Vernon.
“We were honored to be a part of such an important event,” said Ms. Diamond. “It’s inspiring to see different organizations come together to help the community that we are all a part of and to bridge the gap to care and support. This is our community, so this is exactly where we should be. A simple conversation with someone can provide us with enough information to easily connect individuals to life-saving services. For the most part, many of the participants were simply looking for someone to talk to, and it was extremely gratifying for each of us to be that person.”
On February 22, Sabina Lim, MD, MPH, Vice President and Chief of Strategy for Behavioral Health at Mount Sinai Health System; Joan Bell, LCSW, Clinical Director of The Mount Sinai Hospital’s Psychiatry Ambulatory Services; and Anita Kennedy, CRPA, CMA, Peer Engagement Specialist at the Addiction Institute of Mount Sinai at Mount Sinai Beth Israel, provided mental health and opioid/substance use counseling and referrals, distributed more than 50 naloxone kits, and trained 57 people on their use.
Ciarra Leocadio, a REACH patient navigator/outreach worker, provided overdose prevention education and naloxone distribution.
Several volunteers attended from Mount Sinai’s Respectful and Equitable Access to Comprehensive Healthcare (REACH) Program, which provides a patient-centered, harm reduction approach to primary care for persons who use alcohol and other drugs, and for individuals living with hepatitis C. Martha Giardina, RN, a REACH nurse, Katherine Dunham, a REACH patient navigator/outreach worker, and Ciarra Leocadio, a REACH patient navigator/outreach worker, provided overdose prevention education and naloxone distribution. “The work of the REACH Program would not be possible without our strong connection to our community partners; we were grateful to be part of this event and are inspired by the commitment to help those in need of mental health and addiction services,” said Jeffrey Weiss, PhD, MS, Director of REACH and Associate Professor of Medicine.
“I am so proud of and grateful to the Mount Sinai Behavioral Health team who have volunteered at this important community event,” said Dr. Lim. “As clinicians, it is important for us not to wait for people to come in, but to go out into the communities we serve to make the connections. I am also so impressed by and thankful to the Rescue Alliance agencies for organizing this event and for the incredible work they do every day for the homeless.”
Updated on Jun 30, 2022 | Psychiatry
Due to the team’s consistent engagement and follow-up, 98 percent of patients involved with MOT intervention have shown up for their first appointment.
As part of the state’s ongoing effort to further innovate in behavioral health care and develop more effective alternatives to emergency rooms, the New York State Office of Mental Health (OMH) asked Mount Sinai Morningside (formerly known as Mount Sinai St. Luke’s) to lead the Upper Manhattan Behavioral Health Crisis Response Pilot. This pilot aimed to improve the response times of existing mental health mobile crisis teams (MCTs) and to better ensure follow-up outpatient care. MCTs go out into the community to do clinical in-person assessments for people experiencing a behavioral health crisis, and provide short-term follow-up post-crisis. The goal of the pilot was to reduce response time for individuals served by the Mount Sinai Morningside MCT (increasing the likelihood of face-to-face contact), and also to create a network of outpatient mental health providers committed to providing timely outpatient appointments. Ultimately, the pilot aimed to develop a model of response and post-crisis connections to outpatient care that can be replicated throughout New York City.
The Mount Sinai Morningside team more than exceeded their goals. They reduced response time from 24-48 hours to just two hours, which led to a more than 10 percent increase in face-to-face contact with patients, and ultimately higher outpatient appointment acceptance and attendance rates. Mount Sinai’s success led to the expansion of the pilot into a New York City-wide pilot during the second and third years, and to include Mount Sinai Beth Israel and several other hospitals in New York City. In addition, the Mount Sinai Morningside MCT expanded their geographic catchment area for crisis response.
A data-driven evolution: The mobile outreach team
Part of the charge of the pilot was to develop deep quantitative and qualitative understanding of the nature of behavioral health crises. The data showed that only approximately half of patients who reached out were in a true state of crisis. The other half were at risk of a future crisis because they were disconnected to outpatient treatment or had difficulty getting access to treatment. Early in the test, the team realized they could use MCT resources more efficiently by creating an offshoot mobile outreach team (MOT) to handle the non-crisis cases. This would enable the MCT to reach the patients in crisis more quickly and efficiently, and the MOT could focus on the patients who didn’t require urgent or emergent care. The MOT’s purpose was to proactively try to prevent crises, rather than rapidly respond to crises. And the primary way to try to prevent crises was to engage meaningfully and connect patients to outpatient care.
While the MCT consists of social workers, the MOT is made up of a social worker and a credentialed peer counselor. “This combination is unique,” said Kristina Monti, PhD, LCSW, Director of Special Projects for the Psychiatric ER at Mount Sinai Morningside and Mount Sinai West. “It’s unique to the intervention itself in that it’s providing a transition of care, and it’s focused not so much on crisis intervention but on engagement.”
How it works
The MOT’s social worker, Sara Kluge, LCSW, screens the referrals from various sources within Mount Sinai Morningside and Mount Sinai West (inpatient and outpatient psychiatric services). Once screened, she and the peer counselor, Antonio Muñoz-Hilliard, have their first meeting with the patient, often on the inpatient unit. During this meeting, a rapport is established through supportive engagement; potential barriers to psychiatric stability are identified; and patients are provided with psychoeducation/planning regarding follow-up appointments. “We’ve had a very high engagement rate—in the first year, 97 percent of patients we met with agreed to the service,” Ms. Kluge said.
Within 24 hours after this initial meeting, the two reach out to the patient to arrange a second meeting. This meeting takes place in the community, often in the patient’s home. In this setting, Sara and Antonio work to remove barriers such as transportation to appointments, ambivalence about mental health treatment, and basic needs. This sets the MOT apart from other programs—both the effort to tailor a unique approach for all individuals, and a standard of reaching out to patients within one day of discharge.
The third meeting is the “warm hand-off,” where the team meets the patient at the clinic and helps with paperwork. Due to the team’s consistent engagement and follow-up, 98 percent of patients involved with MOT intervention have shown up for this first appointment. The first clinic visit can often feel daunting. “Some of the patients are only 18 or so, and this is their first time filling out this type of paperwork,” said Sara. “I’ve had patients who would have left if I hadn’t been there to help them through it. Having someone sit and walk them through the process has really increased the likelihood of them attending that next appointment.”
An empathetic perspective
As a peer counselor, Antonio has real-life experience and therefore can engage with the patient on a level that a social worker can’t. He has been a peer counselor for 12 years, and Mount Sinai hired him for the MOT. He provides tools for recovery, serves as a model of sustained wellness in order to provide hope, and aims to help patients focus on the whole picture of their lives. “Sometimes we have to look at what’s happening in the life of the individual to promote a trauma-informed way of relating,” he said. “I like to look at it not from the perspective of what’s wrong, but what happened. If they lost their job, failed at school, ended a relationship, got evicted, are suffering from physical health problems—all these things affect the way that we take care of ourselves and how we view crisis. The focus should not be on what we want to avoid doing, but to encourage a move to who and where we want to be.”
A successful proof of concept
The MOT has an 86 percent retention rate of patients returning to the next appointment and continuing clinic treatment. Providers feel the MOT is a vital part of successful continuity of care. “There are several examples in which MOT involvement has been so essential for transition to our clinic. MOT does such a good job of connecting to patients and using patient-centered interventions,” said Joyce Thomashefsky, LCSW, a Mount Sinai West inpatient social worker. “I feel most comfortable with discharge plans when MOT is involved, as I can see more patients are showing for their appointments,” added Hafina Allen, LCSW, a Mount Sinai Morningside inpatient social worker.
Patients also know who they can go to if they have problems in the future, due to the rapport they have built with the MOT. “MOT saved my life that day,” said one patient. “I was hurting myself and I felt comfortable telling them that when they visited me at home.”
Updated on Jun 30, 2022 | Mental Health, Psychiatry, Your Health
Interest in cannabidiol (CBD) has increased dramatically in recent years. Available in oils, lotions, and vaping fluid, the substance has been touted as a cure-all for various ailments including anxiety, arthritis, and insomnia. While its growing reputation is impressive, is CBD just an alternative medicine fad or can it really help?
For the past decade, Yasmin Hurd, PhD, Director of the Addiction Institute of Mount Sinai, has been at the forefront of CBD research. Below, she breaks down the three things you should know before adding the substance to your routine.
What is CBD and what can it treat?
CBD is one of more than 100 substances known as cannabinoids found in the Cannabis plant. There are two main cannabinoids, CBD and THC (tetrahydrocannabinol). CBD does not cause a high, unlike THC, which is the main psychoactive ingredient in cannabis (including marijuana and hashish).
Although you can find many advertisements touting CBD’s medicinal uses, the U.S. Food and Drug Administration (FDA) has not approved CBD to treat any disorders in adults. The only FDA approval for CBD is for the treatment of two rare and severe forms of childhood epilepsy. However, CBD has been investigated for the treatment of anxiety, cannabis and opioid use disorder, Crohn’s disease, diabetes, epilepsy, pain, Huntington’s disease, sleep disorders, Parkinson’s disease, and schizophrenia/psychosis.
If there is no FDA approval, what evidence supports CBD use?
In limited clinical trials, CBD was found to help reduce social anxiety, post-traumatic stress disorder, and craving in those with an opioid addiction. However, most of these clinical studies involved a small number of participants. For a more conclusive verdict, larger, more sophisticated trials are needed.
Fortunately, more extensive research is in the works. In May 2019, my team published study results from a clinical trial showing that CBD reduced craving and anxiety in individuals with a history of heroin abuse. This suggests that it may play a role in helping to break the cycle of addiction. We are now starting larger studies.
Is CBD safe? If I decide to use it, should I tell my doctor?
Yes and yes. A consistent finding in clinical studies is that CBD is safe. However, it is not FDA-approved and researchers are still investigating its use. Because of this, it is critical that your doctor is aware of your CBD use. Making your doctor aware will help to avoid any potential for CBD to interact with medications you may be taking. Even if you do not take regular medications, you should keep a log of your daily activity, including any changes in your physical state, mood, and sleep following use.
Additionally, because CBD is not regulated by the FDA, you should be careful about the source of your CBD. Many products sold as “pure CBD” contain THC and other ingredients that can be harmful, such as lead, mold, or synthetic cannabinoids, which can cause paranoia, hallucinations, or other psychotic symptoms. For a safer, higher-quality product, look for CBD that has a certificate of analysis—this indicates that the product has been thoroughly checked for contaminants and allows you to view its THC and CBD levels.
Feb 20, 2020 | Psychiatry
Dr. Yehuda’s interest in MDMA-assisted psychotherapy represents the culmination of her 30-year career spent investigating the pathophysiology, treatment, and prevention of PTSD.
MDMA, the psychoactive drug sometimes known as ecstasy, is poised to become a powerful tool in the treatment of PTSD. In 2017, the U.S. Food and Drug Administration (FDA) designated MDMA-assisted psychotherapy as a breakthrough therapy. Although MDMA itself is not officially legal or approved for clinical use, phase III trials are underway, and expanded access status was granted in 2020 in the United States and Israel. The results of preliminary clinical studies are extremely promising, and the FDA could approve MDMA-assisted psychotherapy for PTSD as early as 2023.
Rachel Yehuda, PhD, Director of Mount Sinai’s Traumatic Stress Studies Division, has completed the clinician training for MDMA-assisted psychotherapy sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS). She plans to launch a Center for Psychedelic Psychotherapy and Trauma at Mount Sinai later this year that will focus on MDMA-assisted psychotherapy and other psychedelic-assisted psychotherapies with compounds such as psilocybin. Below, she breaks down the top five things psychiatrists need to know about MDMA-assisted psychotherapy.
1. The backstory. MDMA was first synthesized and patented by the German pharmaceutical company Merck in 1912, but it wasn’t until the 1970s and 1980s that psychiatrists began using it in therapy to enhance communication and introspection. Because MDMA was also used recreationally in ways that could potentially lead to abuse or harm, the U.S. Drug Enforcement Administration banned this compound in 1985, and the FDA designated it as a Schedule 1 controlled substance.
2. How it works. The pharmacologic effects of MDMA involve the release of neurotransmitters such as serotonin, dopamine, and norepinephrine, with a subsequent increased secretion of several hormones such as oxytocin, prolactin, cortisol, and vasopressin. “But these properties do not fully explain the sense of empathy towards self and openness to engage in self-reflection,” said Dr. Yehuda. “People taking MDMA report feelings of energy, well-being, empathy, transcendence, and sensory pleasure, and these are optimal conditions for engaging in processing of difficult or traumatic material.”
3. How it’s administered. A typical MDMA-assisted psychotherapy session involves ingesting 120 mg of MDMA, followed by an optional half-dose of 40 mg administered about two hours after the initial dose to extend the therapeutic effects. The effects can last as long as eight hours, during which the patient has the opportunity to revisit important past events and emotions with two trained therapists. Preparation and integration sessions help the patient consolidate therapeutic gains. Generally, patients receive two or three sessions within a 12-week period.
4. What to tell patients. Patients wishing to try MDMA-assisted psychotherapy should do so within the context of a clinical trial until the treatment is approved by the FDA. Taking MDMA recreationally will not produce the therapeutic effects associated with MDMA-assisted psychotherapy because the goal of the treatment is to provide an opportunity for processing painful emotions under the guidance of trained psychotherapists. There are some contraindications for taking MDMA, so patients must undergo a physical clearance process. However, MDMA has an acceptable safety profile if administered according to the protocol. Patients interested in participating in the study should visit mdmaptsd.org.
5. The evidence. “MDMA-assisted psychotherapy has demonstrated greater therapeutic efficacy than any other psychotherapy or medication for PTSD,” said Dr. Yehuda. Unlike with many other therapies for PTSD, symptom reduction can be maintained after a single course of treatment by most patients. And the effects last—more than two-thirds of patients receiving MDMA-assisted psychotherapy no longer had PTSD when measured one year later. Researchers attribute these outcomes to MDMA’s unique ability to allow patients to examine traumatic experiences without experiencing the attendant pain, which enables them to work through the issue with their therapist.
Dr. Yehuda’s interest in MDMA-assisted psychotherapy represents the culmination of her 30-year career devoted to identifying biological alterations in PTSD and resilience, and developing novel treatment approaches for the prevention and treatment of PTSD. Her Center for Psychedelic Psychotherapy and Trauma Research uses clinical trials, computational genetics, molecular biology, blood samples, and neuroimaging to accelerate understanding of how MDMA and psilocybin work. The center also holds clinical trainings for therapists in anticipation of FDA approval and leads public and scientific education, including a monthly lecture series.
If you find our research and clinical experience valuable for the field and your patients, please consider voting for The Mount Sinai Hospital via Doximity in the U.S. News & World Report Best Hospitals rankings for Psychiatry. Your vote helps make it possible for us to continue to uncover and explore paths to prevention and treatment of psychiatric disorders.
Dr. Yehuda is a Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai, where she is also the Vice Chair for Veterans Affairs in the Department of Psychiatry as well as Director of the Traumatic Stress Studies Division. This division includes the PTSD Clinical Research Program and the Neurochemistry and Neuroendocrinology Lab at the James J. Peters VA Medical Center in the Bronx. Her PhD is in psychology and neurochemistry, and her MS is in biological psychology.
Updated on Jun 30, 2022 | Psychiatry
From left: Dennis S. Charney, MD; Nora Volkow, MD; Yasmin Hurd, PhD; Sabina Lim, MD, MPH, Professor of Psychiatry, Icahn School of Medicine at Mount Sinai, and Vice President and Chief of Strategy, Behavioral Health, Mount Sinai Health System; and Eric J. Nestler, MD, PhD.
Luminaries in addiction research, policy, and clinical care, led by keynote speaker Nora Volkow, MD, Director of the National Institute on Drug Abuse (NIDA), participated in an all-day conference in the fall hosted by the Addiction Institute of Mount Sinai (AIMS) at the New York Academy of Medicine.
“Today is about solutions,” said AIMS Director Yasmin Hurd, PhD, Ward-Coleman Chair of Translational Neuroscience, as she welcomed guests to the “Confronting Addiction: Science, Policy, and Care” conference. “Our objective is to start a dialogue among scientists, policymakers, and clinicians so we can create more opportunities to collaborate on developing more effective treatment strategies, support structures, and policy infrastructure for people and families struggling with addiction.” Dr. Hurd, a world-renowned researcher in the neurobiology of addiction disorders, is also Professor of Psychiatry, Neuroscience, and Pharmacological Sciences at the Icahn School of Medicine at Mount Sinai. Her remarks were followed by introductions from Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai, and President for Academic Affairs for the Mount Sinai Health System, and Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience, Dean for Academic and Scientific Affairs, and Director of The Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai.
In her speech, “The Role of Science in Substance Abuse Policy and Care,” Dr. Volkow challenged the audience: “When I first came to Washington, D.C., as Director of NIDA, one of the most frustrating things was my naïve perception that policy would be guided by science—and it’s not.” She asked: “So what do we need to do to make sure it’s not ignored? What can we, as scientists, do to increase the likelihood that our evidence-based findings are implemented into policy?”
The event also included discussions on four key topics: Taking Addiction Policy into the 21st Century; Early Predictors of Addiction; Objective Assessment of Addiction Symptoms and Treatment Outcomes; and New Frontiers in Addiction Treatment.
