By Kat Procyk
Photography by Tom Altany/University of Pittsburgh
Major depression is one of the most common mental health disorders in the United States, affecting an estimated 21 million adults per year.
Rebecca Price, associate professor of psychiatry, School of Medicine, is developing innovative therapies that rapidly relieve patients of depression symptoms, like persistent sadness and hopelessness, and retrain the brain’s thought patterns to improve the perception of self-worth with lasting results.
The condition is caused by a complex interplay of factors like genetics, stress, personality traits and medical conditions. Some individuals are more susceptible to major depression than others. Though, people of any race, sex or age can experience it.
Several treatments for major depression exist, with psychotherapy and antidepressant medications being considered among the most effective; however, remission rates are low, and relapse rates are high. Some patients are treatment-resistant from the start.
Price’s approach shows promise in making a difference, even for them.
"I first got interested in mechanistically targeted techniques, like brain retraining, because of my background in cognitive science,” said Price, who is also associate professor of clinical and translational science, health sciences; and of psychology, Kenneth P. Dietrich School of Arts and Sciences. “I liked the idea of measuring how the brain processes information and using that information to design targeted neurocognitive interventions that could be therapeutic or beneficial."
Retrain the Brain
Price developed new computer-based exercises called Automated Self-Association Training (ASAT). During these exercises, patients are shown repeated groups of self-related words and images paired together with positive cues. A patient, for example, could be shown a photo of themself followed by a photo of a stranger smiling. Such pairings can be repeated hundreds of times within the space of a few minutes.
The goal is to harness the brain’s neuroplasticity—its ability to form and reorganize synaptic connections—which supports learning and recovery from injury.
However, patients may require an external stimulus to boost neuroplasticity and unlock the benefits of ASAT. In Price’s previous study, published in the American Journal of Psychiatry, participants received a single low-dose infusion of ketamine—an anesthetic known for its rapid antidepressant effects, achieved by quickly enhancing neuroplasticity. Patients were then enrolled in ASAT after the infusion.
And it worked.
Patients who received a ketamine infusion and the training reported an immediate reduction in depression symptoms that continued for about 90 days.
The Cost of Ketamine
Still, the use of ketamine has its pitfalls. An infusion of ketamine, on average, can cost $400 or more without insurance coverage, must be administered in a doctor’s office and is time-consuming. Excluding transportation, an infusion takes approximately 40 minutes and another hour to recover from the sedative effects.
“It’s not practical for the average person,” Price said. “So, as the patient, what are you going to do? Show up at your doctor’s office for an infusion every week for the rest of your life? We can’t expect that.”
The drug can also induce a dissociative state for some patients. Reactions are mixed, with a smaller portion of patients saying the reaction caused anxiety while most say it has a calming effect. Nevertheless, infusions require careful clinical monitoring of the patient’s cognitive state, during and after the infusion.
Bringing Mental Health to Market
Price is now partnering with Syndeio Biosciences, a clinical-stage biotechnology company, for an investigator-initiated study to test their new drug candidate, apimostinel, as a substitute for ketamine.
Apimostinel, like ketamine, acts on N-methyl-aspartate (NMDA) receptors in neurons to increase the neurotransmitter glutamate and the release of brain-derived neurotrophic factor (BDNF), a protein that helps repair and grow neurons. But unlike ketamine, apimostinel targets the NMDA receptor in a different way to avoid the dissociative “trip” that patients often experience with ketamine. Syndeio Biosciences believes apimostinel’s safer approach, delivered as a rapid injectable drug versus instead of a 40-minute infusion, gives patients and doctors a more attractive alternative to ketamine.
These new approaches by both ketamine and apimostinel may make the brain work better and lift moods faster than conventional antidepressants. Typically, it can take around four to six weeks of daily dosing of antidepressants for patients to start seeing benefits of treatment. Combined with apimostinel, Price’s therapy has the potential to significantly extend relief time, meaning a patient may need to take medication only intermittently.
Together, as of December 2024, Price and Syndeio Biosciences are conducting a trial of apimostinel combined with ASAT, like Price’s ketamine study.
“We’re very excited to be partnering with Dr. Price,” said Michael G. McCully, president and COO of Syndeio Biosciences. “The ASAT tool has already shown promising results that underscore neuroplasticity and synaptic function, making it an ideal treatment alongside apimostinel.”
Price recently joined Pitt’s Innovation Institute and through their partnership, patent applications for ASAT, either with or without plasticity-boosting agents like ketamine or apimostinel, are currently being filed in multiple countries.
Price never intended to be an entrepreneur, but she dreams that it will lead to a long-term outcome of relief for mental health patients worldwide.
“Bringing this therapy to market isn't just about innovation—it's about impact,” Price said. “Every step toward commercialization is a step closer to someone getting their life back.”
A senior University official has financial interests in the study sponsor, Syndeio Biosciences.