Precision Neuromodulation for Treatment-Resistant Depression

For millions of people, depression is a persistent and often disabling illness. Despite decades of research and new medications, many people continue to struggle even after trying multiple forms of treatment. Known as treatment-resistant depression, this condition affects people who find little or no effective relief from conventional therapies and who often face limited options for recovery. 

We approach brain health with scientific precision and human understanding. One of the most promising, proven therapies we offer is SAINT^®, or Stanford Accelerated Intelligent Neuromodulation Therapy. Developed at the Stanford Brain Stimulation Lab, SAINT is the first FDA-cleared, rapid-acting neuromodulation therapy for severe depression, and the first to use functional MRI to map out an individual’s brain connectivity to identify the optimal anatomic region for stimulation. 

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Understanding the Circuitry of Depression

Modern neuroimaging has reshaped how we understand major depressive disorder (MDD). Rather than a chemical imbalance, depression is increasingly recognized as a disorder of the brain networks that regulate thought and emotion. Two regions are particularly important in this process. The dorsolateral prefrontal cortex, or the DLPFC, helps with emotional regulation and cognitive control. The subgenual anterior cingulate cortex, or sgACC, processes emotion and internal states.

In people with depression, the DLPFC is often underactive while the sgACC becomes overactive. This imbalance limits the brain’s ability to shift out of negative self-focused thought patterns and contributes to persistent low mood. SAINT works by restoring balance between these two regions. 

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How SAINT Works

SAINT utilizes a combination of structural and resting-state functional MRI to find the exact spot in the DLPFC that connects most strongly to the sgACC. Once identified, treatment begins with focused neuromodulation to help regulate activity in this network. Each session lasts about 10 minutes. People receive 10 sessions a day for five consecutive days, with 50-minute breaks between sessions where they can rest, catch up on emails or listen to a podcast. This structure is based on the principle of spaced learning, which shows that short, repeated intervals of stimulation create stronger and longer-lasting effects on brain activity.

SAINT’s high-dose intermittent theta-burst stimulation helps the brain build new, healthy patterns of connectivity. Many people begin to notice improvement within days instead of weeks or months. 

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Evidence and Outcomes

Clinical trials at Stanford University and other institutions have shown remission rates approaching 80% in patients with treatment-resistant depression after a single five-day course of SAINT. In a double-blinded randomized controlled trial, 79% of participants receiving SAINT achieved remission compared to just 13% who received a placebo treatment. These findings confirm that personalized, MRI-guided targeting enhances outcomes compared to standard stimulation methods.

Additional studies have found that SAINT may also correct abnormal signaling between the anterior cingulate cortex and the insula, providing a potential biomarker for treatment response.  Research also shows no significant cognitive side effects, and in some cases, people demonstrate improved attention and executive functioning following treatment.

SAINT therapy is cleared by the U.S. Food & Drug Administration (FDA) for the treatment of MDD in adults who have not improved with antidepressant medication (FDA, 2022). It is also being studied for other conditions such as postpartum depression, obsessive-compulsive disorder, bipolar disorder and other neuropsychiatric conditions. 

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Integrating SAINT into Precision Brain Healthcare

At Salma Health, SAINT is part of a connected care system that combines advanced diagnostics, imaging and biomarker analysis to tailor treatment to each person’s needs. We integrate neuromodulation with complementary interventions, such as pharmacology, cognitive therapy, and addressing co-occurring neurological disorders, to match each patient with the approach most likely to deliver effective relief.

Our approach emphasizes continuous monitoring and collaboration among medical professionals. Every patient’s plan adapts over time as we track outcomes and adjust treatments to sustain progress. This model ensures that recovery remains a guided, supported process rather than care at a single point in time. 

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Looking Ahead

Depression remains the leading cause of disability worldwide, yet research continues to reveal new ways to intervene more effectively. SAINT represents a new era of precision psychiatry, one where imaging, data and targeted therapy work together to repair the brain’s natural rhythm of regulation and balance. 

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I had the honor of working with Dr. Nolan Williams at Stanford University’s Brain Stimulation Lab on the development and testing of SAINT. Our work focused on understanding the brain’s circuitry to develop new ways to treat major depression with greater precision and speed. That experience shaped how I view psychiatry and the possibilities of neuroscience. I later co-founded Magnus Medical to bring this therapy into clinical practice and make it widely available. I then worked with Nolan and our founding team to create Salma Health, a system of brain healthcare that combines science, compassion and innovation. My work will be forever dedicated to the vision Nolan gifted to us to all.