The growing need for mental health services is “the next pandemic” according to the American Hospital Association. The COVID-19 pandemic had a pervasive impact on individuals’ mental health worldwide and brought mental health into acute focus. All mental health issues merit discussion, but here we will focus on depression.

Even before the pandemic, the World Health Organization (WHO) recognized depression as a leading cause of disability worldwide, contributing to poor performance at work, in school and in personal lives. In fact, researchers estimate that every year nearly 7% of adults in the U.S. experience depression. A new report published by the U.S. Centers for Disease Control and Prevention (CDC) suggests that “During 2020, approximately one in five U.S. adults reported having ever received a diagnosis of depression by a health care provider, with prevalence of depression higher in women, younger adults, and adults with lower education levels.” The report also notes that “the prevalence of depression overall was 24% among women compared with 13% among men, and 21.5% in younger adults ages 18 to 24 versus 14.2% in adults 65 and older.”

There are different types of depression, some of which are harder to treat than others. Major depressive disorder (MDD), one of the severest forms of depression, is an episodic disorder that can last months or years and is the leading cause of disability worldwide. The WHO has stated that more than 280 million people suffer from MDD globally; nearly half of those have treatment-resistant depression (TRD); and far too many people with MDD experience suicidal thoughts with no rapidly acting treatment options available to them.

Causes and Impacts of Depression and MDD

Several factors contribute to depression, including brain chemistry, genetics, stressful life events, medical conditions and medication. Neurons absorb and process new information and then transmit electrical and chemical signals. Billions of neurons in the brain are linked together to form complex neural networks. When one neural network in the brain increases in activity, there’s a see-saw reduction in the activity of the other networks. The brain shifts between neural networks appropriate to the specific task a person focuses on—driving a car, writing an essay, playing the piano, etc.

When someone suffers from depression, or MDD, it’s like they are stuck in one neural network. Two neural networks are closely associated with the onset of depression and its symptoms:

  1. The default mode network (DMN), which consists of areas of the brain responsible for managing emotions and is associated with ideation and identification of “the self”; and

  2. The central executive network (CEN), which comprises parts of the brain that manage high-level (executive) cognitive functions, including processing complex thoughts, behavior, planning, multi-tasking and motivation.

The growing need for mental health services is “the next pandemic” according to the American Hospital Association.

The DMN and the CEN are also associated with the efficacy of antidepressants. When CEN connectivity is low, research has found that the efficacy of antidepressants can be predicted to be poor. In patients with MDD, the connections between the DMN and the CEN are sparse and unchanging, whereas people without depression exhibit stronger and more variable connections. Researchers have found that network disruptions between the CEN and DMN relate to the severity of depression, and impacts to these networks can also impair people’s cognitive abilities due to their depression. Studies have shown that depression can significantly impact attention, memory, ability to process information and decision-making. Depression can also impact cognitive flexibility and executive functioning—the core brain processes that allow people to adapt to their surroundings and get things done.

People with depression, especially those with treatment resistant major depression, can feel helpless and hopeless, as though a pervasive dark mood is consuming them.

SAINT™: A Promising New Treatment for MDD

Common treatments for depression—antidepressants, cognitive behavioral therapy (talk therapy), and transcranial magnetic stimulation—often don’t help people suffering from MDD. Fortunately, a novel treatment—the SAINT™ Neuromodulation System—has proven to be effective in treating severe depression.

The SAINT Neuromodulation System uses structural and functional magnetic resonance imaging (MRI) of brain activity to identify the most strongly connected portions of the left dorsolateral prefrontal cortex (DLPFC) with respect to the subgenual anterior cingulate cortex (sgACC), a deeper subregion of the brain. In people who have MDD, the DLPFC is underactive and the sgACC is overactive, which impairs their ability to stop or block out inwardly directed negative thoughts. Locating the specific therapy target in each person is achieved by imaging a patient with both structural MRI and resting-state functional connectivity MRI to precisely find the spot where the DLPFC is connected to the deeper network.

By precisely stimulating part of the DLPFC, SAINT reduces activity in the sgACC, and restores mood regulation. The SAINT Neuromodulation System stimulates this precise region with a specialized, high-dose pattern of repetitive magnetic pulses that induce neurons to fire. This form of stimulation can safely and effectively modify activity in brain networks related to major depression.

People treated with the SAINT Neuromodulation System undergo a 5-day course of high-dose intermittent theta burst stimulation that delivers 1,800 pulses per session. Patients have 10 sessions per day with a 50-minute interval between each session. The SAINT protocol is based on the spaced learning theory: neuroplastic changes are more robust when a stimulus is repeated while allowing an appropriate interval of rest. Take for example the practice of studying flashcards before a test. Hours of continuous studying is not as effective as when a person takes breaks in between periods of studying, like when they use flash cards.
Conventional treatments for treatment-resistant depression take weeks to months to begin working and provide remission from depression for only a fraction of people.

Promising Clinical Results

Typically, in non-depressed people, the anterior insula (the part of the brain that supports sensation and subjective feelings) sends signals to the bilateral anterior cingulate cortex (ACC), but in 80 percent of people with depression, the ACC sends signals to the anterior insula. Results of a study published in 2023 suggest that treatment with SAINT for MDD reverses the direction of these abnormal brain signals. Moreover, this reverse signaling may serve as a biomarker for diagnosing and treating major depressive disorder.

In clinical trials, treatment with SAINT for major depressive disorder has resulted in a significant reduction in depressive symptoms at four-weeks post-treatment following the five-day treatment. In addition to showing no negative cognitive side effects after being treated with SAINT, a double-blinded randomized controlled trial (RCT) showed that some cognitive function improved after treatment, notably the ability to tune out thoughts that are irrelevant to the task or process at hand, referred to as cognitive inhibition. And, conclusive results from the RCT showed that 79% of people in the active treatment arm experienced significant reduction of their depression symptoms compared to 13% of people in the sham treatment arm.
Overall, SAINT has been shown to be effective in the treatment of MDD, with approximately 80–90 percent of people achieving remission from their depression symptoms following the five-day SAINT treatment.

Why SAINT Is Important

A critical need exists in the U.S. and globally for an effective therapy for treatment-resistant depression. The SAINT Neuromodulation System is an FDA-approved treatment for MDD, a hard-to-treat form of depression. With SAINT treatment and appropriate follow-up therapy, people can experience improved mood and cognitive functions. Currently, the SAINT Neuromodulation System is being evaluated in an Open Label Optimization (OLO) clinical trial at multiple sites throughout the U.S. Up to 1,000 participants will be enrolled. For more information, please visit