The development of innovative treatments provides great reason for hope in mental healthcare, despite this time of increasing need and novel challenges.
“I’m witnessing a greater ability to address difficult-to-treat illnesses than I have ever seen,” says Scott Aaronson, MD, chief science officer, Institute for Advanced Diagnostics and Therapeutics at Sheppard Pratt. “Even for a skeptical, cynical scientist like me, I predict that psychiatry will change more in the next decade than it has in the last century.”
From new FDA approvals to improved existing treatments, a host of innovations are set to transform psychiatry and the well-being of patients. We spoke with experts to explore some of the most exciting advances.
Progress for postpartum depression
The FDA’s recent approval of the first oral medication specifically developed to treat postpartum depression (PPD) gives clinicians a welcome new option to help mothers. Zuranolone (brand name Zurzuvae) is taken daily for two weeks and has been shown to ease PPD symptoms in just three days, a drastic improvement over the three to four weeks antidepressants can take to become effective.
Its mechanism of action is similar to brexanolone (brand name Zulresso), the only other FDA-approved medication for PPD, but Zulresso is administered via a 60-hour intravenous infusion in a hospital. “Having a medication that can be taken orally is a significant change. Mom no longer must be away from her newborn for 60 hours. This treatment can be more widely used, and it can be used on an outpatient basis without having to directly supervise the patient,” says Deval Zaveri, MD, director of Sheppard Pratt’s Women’s Mental Health Program and medical director of the Emergency Psychiatry program at Greater Baltimore Medical Center (GBMC).
Dr. Zaveri explains that while psychotherapy remains the first line of treatment for mild PPD, medication management plays a vital role in treating moderate and severe cases. Patients who have responded well to antidepressants in the past should start by trying those, but Zurzuvae can be considered for patients with moderate symptoms and no history of psychiatric illness.
Zurzuvae’s most common side effects include sleepiness, dizziness, and diarrhea. It hasn’t been studied sufficiently in breastfeeding women but is known to pass into breast milk, making its safety for babies unknown at this time.
"For years, there hasn’t been a lot of research into postpartum depression. This investment is a step in the right direction and has definite advantages over existing options,” says Dr. Zaveri.
MDMA closer to FDA approval
One of the studies, published in Nature Medicine in September 2023, included 104 ethnoracially diverse participants with moderate to severe PTSD, many with a history of suicidal thoughts and comorbidities such as alcohol use disorder. PTSD symptoms were significantly reduced in participants who received MDMA with psychotherapy compared to those given a placebo along with psychotherapy, with 71% of MDMA participants improving so much that they no longer met DSM-5 diagnostic criteria for PTSD at the end of the study.
“This is probably the most dramatic development that will happen in the next year,” says Dr. Aaronson. “It’s monumental given that it is repurposing a previously illegal drug for psychiatric use, plus it will be the first time a drug will need to be administered along with psychotherapy. This is a huge leap for patients with PTSD, a distinctly underserved population within mental health.”
“It’s monumental given that it is repurposing a previously illegal drug for psychiatric use, plus it will be the first time a drug will need to be administered along with psychotherapy. This is a huge leap for patients with PTSD, a distinctly underserved population within mental health.”
Treatment included three eight-hour dosing sessions followed by three weeks of therapy after each dose. “During the MDMA sessions, you’re working with the study subject as they’re delving into their prior trauma and finding new ways to cope with it,” says Dr. Aaronson.
Although the Drug Enforcement Administration (DEA) lists MDMA as a Schedule 1 agent, considering it to have no accepted medical use and a high potential for abuse, it has been granted “breakthrough therapy” designation by the FDA. Approval could come in mid-2024.
The promise of psilocybin therapy
The Center of Excellence for Psilocybin Research and Treatment at Sheppard Pratt is at the forefront of innovative treatments for depressive disorders. As a center of research, it’s the leading site of a phase 3 trial of psilocybin therapy for treatment-resistant depression (TRD).
“Our target is treating depression in patients who have failed two to four treatments in the current episode of depression,” says Dr. Aaronson. “Since the odds of responding to a third treatment for depression are 25% or less after two failed treatments, finding novel treatment options for these patients is critical.”
Psilocybin, a naturally occurring psychedelic chemical found in certain mushrooms, is thought to make the brain more flexible and can be used with psychotherapy to change entrenched thinking patterns.
Psilocybin is currently a Schedule 1 agent, with the FDA’s “breakthrough therapy” designation for treating TRD and major depressive disorder (MDD).
But it’s not just TRD and MDD where psilocybin is showing promise as an effective treatment option. Researchers at Sheppard Pratt are also studying the treatment of anorexia and bipolar II disorder with psilocybin. Other research is unearthing the benefits of psilocybin therapy for treating PTSD, obsessive-compulsive disorder (OCD), anxiety, and substance use disorders.
“Almost any illness that constricts your thinking is a potential target,” says Dr. Aaronson.
New and improved TMS
Transcranial magnetic stimulation (TMS) to treat MDD has been FDA-approved and used since 2008. More recently, it was approved as a treatment for OCD and anxiety symptoms in adults.
While not yet approved for use with adolescents, Dr. Aaronson is hopeful that will change. “The data has been problematic because kids have such a high placebo response rate,” he says. “In a recent study, we didn’t separate between sham and active treatment, but we certainly saw a very high level of response. We are preparing to make a plea to have it approved.”
TMS for treatment of TRD was approved in 2022 with the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol. SAINT is a type of TMS treatment that uses MRI to target the region of the brain most needing stimulation. SAINT treatment takes place over only five days compared to five to six weeks for regular TMS.
Studies have shown a rapid and sustained reduction in symptoms in adults with TRD when treated with the SAINT protocol. For example, a study published in The American Journal of Psychiatry reported that participants who received SAINT experienced an average 62% drop in their Montgomery-Åsberg Depression Rating Scale (MADRS) scores compared with a 14% reduction in participants receiving sham stimulation. After four weeks, 69% of the SAINT group had at least a 50% improvement in the MADRS score.
Looking forward
Researchers at Sheppard Pratt and our peer facilities nationwide are dedicated to finding innovative ways to address difficult-to-treat psychiatric illnesses.
“We know treatment as usual does not work for everyone, so it’s our goal to continue to seek new options to help those who are still searching for relief from their disorders,” says Dr. Aaronson.
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Featured Experts
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Scott Aaronson, MD
Chief Science Officer, Institute for Advanced Diagnostics and Therapeutics; Psychiatrist, The Retreat at Sheppard PrattSpecialties:Adult Psychiatry, Biological Psychiatry, Depression, Medication Management, Mood Disorders, Psychopharmacology, Transcranial Magnetic Stimulation (TMS), Treatment-resistant Depression -
Deval Zaveri, MD
Medical Director, GBMC Emergency Psychiatry ServicesSpecialties:Adult Psychiatry, Electroconvulsive Therapy (ECT), Neurology, Women's Issues
The Institute for Advanced Diagnostics and Therapeutics
The Institute for Advanced Diagnostics and Therapeutics brings expert clinical care of difficult-to-treat illnesses together with a center of research developing brand new treatment modalities.