Psychiatry is undergoing a seismic shift, and nowhere is this transformation more evident than in the treatment of depression that has proven resistant to traditional approaches. At the forefront of this evolution is Dr. Scott Aaronson, chief science officer at Sheppard Pratt, whose pioneering work is charting new territory in the battle against difficult-to-treat depression. Through decades of clinical research, Dr. Aaronson and his colleagues have helped redefine the possibilities of recovery for patients who once had little hope.
Dr. Aaronson is a vocal proponent of changing the language we use to describe persistent depression. He advocates for the term “difficult-to-treat depression” in place of the more stigmatizing “treatment-resistant depression.” This shift in terminology reflects a deeper understanding: The challenge isn’t that patients are resistant, but that traditional treatments often fall short in the face of complex and chronic illness.
Many of the patients Dr. Aaronson treats have failed upward of 10 different treatments. They are often, in his words, “fully disabled by virtue of their depression,” with many living for decades in the grip of suicidality and hopelessness. Yet, within this clinical population, Dr. Aaronson is documenting remarkable progress through cutting-edge interventions.
Vagus nerve stimulation (VNS) is one such intervention showing promise where others have failed. Though approved by the Food and Drug Administration (FDA) in 2007, VNS has long struggled to gain mainstream traction due to limited insurance coverage, long time course to see improvement (often six to twelve months), and a narrow view of treatment success. Dr. Aaronson has been a principal researcher in a landmark Medicare-funded study known as RECOVER, examining the efficacy of VNS in patients with chronic, severe depression. What sets this research apart is its emphasis on quality of life and functionality, not just symptom reduction. “Traditional depression rating scales didn’t capture the depth of change we were seeing. But when you look at whether someone can get off the couch, ride a bike again, or simply wake up without suicidal thoughts, you realize that the treatment is making a real difference,” he notes. This reorientation of success metrics is central to Dr. Aaronson’s philosophy: treat the person, not just the diagnosis.
On the other end of the therapeutic spectrum lies one of the most rapidly acting interventions in psychiatric history: psilocybin, a psychedelic compound currently undergoing extensive clinical trials. Dr. Aaronson has led multiple studies exploring psilocybin’s impact on individuals with chronic depression, bipolar II depression, and even chronic suicidal ideation.
The results are nothing short of remarkable. In one study, 60% of participants who had failed five or more treatments reported meaningful improvements after a single dose. Another study of patients with bipolar II depression found 12 out of 15 in remission 12 weeks post-treatment. The potential is profound, yet Dr. Aaronson cautions that we are still early in understanding how best to administer these substances.
“My guess is that psilocybin may ultimately be used two or three times per year, per person, maybe as a ‘booster’ over time,” he says. But key to its success is context: psychedelic therapies must be delivered in safe, structured environments with clinical oversight. Misuse, particularly in unregulated or recreational settings or with individuals at risk for psychosis, jeopardizes both efficacy and patient safety.
Another area where Sheppard Pratt has led the mental health field is in transcranial magnetic stimulation (TMS), an FDA-approved, noninvasive neuromodulation technique for depression. Dr. Aaronson spearheaded Sheppard Pratt’s TMS program for a decade and continues to mentor others innovating in the space.
Novel protocols are pushing the boundaries of TMS, including the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, which administers intermittent theta-burst stimulation multiple times a day with highly promising outcomes. Looking ahead, Dr. Aaronson is particularly intrigued by advances in brain circuit-based interventions. Unlike traditional approaches that stimulate general regions of the brain, emerging methods aim to target specific circuits implicated in depressive states.
Technologies like pulsed ultrasound are also gaining attention. This technique could enable clinicians to deliver drugs directly to targeted areas in the brain by “popping” microcapsules via focused sound waves. Such precision holds the potential to revolutionize both neuromodulation and pharmacologic interventions.
While depression remains the central focus of Dr. Aaronson’s work, Sheppard Pratt is already expanding its clinical trials into adjacent areas, including generalized anxiety disorder, adjustment disorders due to medical illness, post-traumatic stress disorder, and even substance use disorders. Psilocybin, in particular, shows promise in addressing a wide range of psychiatric conditions characterized by rigid, narrowed cognitive and emotional patterns.
Ultimately, what ties all of Dr. Aaronson’s work together is the reintroduction of hope. For people who have been failed by the system, the mere act of being heard, of being offered something new, can spark a profound shift. “When you’ve been told there’s nothing left to try, and then you enter a study that treats you like a person rather than a diagnosis, that hope alone can be therapeutic.”
At Sheppard Pratt, the future of psychiatry isn’t just arriving—it’s being built. Through an arsenal of innovative treatments and a deeply human-centered approach, clinicians like Dr. Aaronson are dismantling despair and making room for recovery where none seemed possible.
The Institute for Advanced Diagnostics and Therapeutics
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