Searching for Alternatives to Antidepressants? A New Option for Treatment-Resistant Depression

Many people living with depression spend months cycling through medications, waiting to see if symptoms will ease. For some, relief never fully arrives. Side effects linger, daily life feels harder than it should, and progress comes slowly—if at all.

That experience has led growing numbers of patients and clinicians to look beyond traditional prescriptions and explore alternatives to antidepressants that work differently and act more quickly. For decades, antidepressants were the best tools we had, based on the knowledge of the time. But just as medicine has advanced in treating the heart or the lungs, our understanding of the brain has undergone a revolution.

We now understand that mood disorders are often rooted in specific brain circuitry and when these circuits become “stuck” or disconnected, it can lead to the symptoms of TRD. This knowledge has paved the way for precision treatments that don’t bathe the whole brain in a chemical, but instead target the exact “on switch” for mood regulation. Brain health treatment can now offer a new path toward remission and stability.

Key Takeaways

• Many people living with depression do not improve with antidepressant medication alone. Only 25% of people achieved remission with their first antidepressant, and just 35% had success after trying four different medications.¹
• SAINT® Depression Therapy is an FDA-cleared, medication-free depression treatment for adults with major depressive disorder who did not respond to prior antidepressants.
• Clinical trials show a 79%² remission in an average of 2.6 days³.
• Treatment is non-invasive and completed in just five days.
• Therapy is personalized using fMRI-guided brain targeting.

Why Antidepressants Don’t Work for Everyone

Antidepressants can be effective for many people, but they don’t always work for everyone. Finding the right medication often involves weeks of waiting, adjusting doses, or switching prescriptions entirely. During that time, symptoms may continue to worsen or interfere with work, relationships, sleep, daily routines, and quality of life.

Some people experience side effects that make it hard to continue treatment, while others see only limited improvement even after several medication changes. When depressive symptoms persist despite trying one or more antidepressants at a therapeutic dose, clinicians describe this as treatment-resistant depression.

This experience is common and does not reflect a lack of effort or willpower. Research shows that patients with TRD have a 138% higher risk of psychiatric hospitalization, more than double the rate of those who respond to traditional treatments.⁴ It is one of the main reasons people begin searching for alternatives to antidepressants that work differently and more effectively.

A Different Kind of Alternative: What Is SAINT Depression Therapy?

SAINT Depression Therapy is an FDA-cleared, non-invasive treatment for adults with major depressive disorder who have not improved with antidepressant medication.

Developed at Stanford University and licensed to Magnus Medical, it uses targeted brain stimulation to influence the specific brain networks known to play a role in mood regulation. The treatment is completed over one week and is designed to target the brain’s neural circuitry without relying on medication, making it a clinically validated option for people living with treatment-resistant symptoms of depression. Although SAINT is a medication-free treatment, some individuals may be instructed by their SAINT provider to maintain their use of medications during and/or after treatment. 

How SAINT Works: Precision Brain Targeting With fMRI

Treatment begins with a clinical consultation with a Verified SAINT Provider to answer questions and to confirm that SAINT Depression Therapy is an appropriate and safe option for the patient.

Patients then undergo structural MRI and functional MRI (fMRI) scans to map the brain’s anatomy and neural activity. Essentially, if a standard MRI is the car, the fMRI is the traffic. While the MRI shows us the physical “vehicle” of your brain, the fMRI shows us the flow of information between those regions. These scans provide detailed information about how regions of the brain involved in mood regulation are connected and where they might need a boost. 

Magnus Medical’s proprietary algorithm analyzes this data to identify each patient’s optimal stimulation target. Accelerated intermittent theta burst stimulation (iTBS) is then delivered to this personalized location, allowing treatment to be tailored to the individual rather than using a one-size-fits-all approach.

Clinical Results

In clinical trials of adults with major depressive disorder who did not improve with antidepressant medication, SAINT Depression Therapy achieved a 79% remission rate after a five-day treatment course.²

Many participants experienced improvement quickly, with an average time to remission of 2.6 days³. Outcomes vary by individual, but these results show that SAINT may function as a fast-acting depression treatment compared with traditional medication approaches that often take weeks to evaluate.

SAINT is FDA-cleared for this use and is intended to support recovery toward remission, not to replace ongoing clinical care.

How SAINT Compares to Traditional TMS

Standard transcranial magnetic stimulation (TMS) typically involves one session per day over six to nine weeks and uses the same general brain target for most patients.This results in individuals having to take extended time away from family and work obligations.

SAINT follows a different model. It uses fMRI-guided personalization to identify a patient’s unique stimulation target and delivers treatment in multiple short sessions each day over five consecutive days. 

Both treatments are non-invasive and performed in outpatient settings, but SAINT compresses the treatment timeline and individualizes targeting based on brain imaging. For some patients, this makes it a practical option when evaluating different antidepressant alternatives.

What Treatment Is Like

SAINT Depression Therapy is completed over five consecutive days in an outpatient clinic.

Each day includes ten short stimulation sessions, each lasting ten minutes, with rest periods of 50 minutes between sessions. Most patients spend the day at the clinic and return home in the evening. They are welcome to bring a support person, as well as books, devices, or a pillow to stay occupied and rested during breaks. 

The total stimulation time is relatively brief, but the schedule allows the brain to respond between sessions as treatment progresses throughout the week. The breaks harness the brain’s neuroplasticity to strengthen new, healthy neural pathways. 

Safety, Side Effects, and Eligibility

SAINT is non-invasive and does not require anesthesia or surgery.

The most commonly reported side effects are mild to moderate headaches or temporary discomfort at the treatment site. This treatment is not recommended for patients with certain metal implants near the head or implanted electronic devices such as pacemakers.

Eligibility is determined by a clinician and includes a diagnosis of major depressive disorder, prior lack of improvement with antidepressant medication, and the absence of medical conditions that would make the treatment unsafe.

Access, Insurance, and Finding a Provider

SAINT Depression Therapy is available through a growing network of verified providers in hospitals and outpatient clinics around the United States

Medicare has finalized payment stability for 2026 under the outpatient prospective payment system, using CPT codes 0889T–0892T. Many private insurers also provide coverage following medical review and prior authorization.

Patients and clinicians can locate providers through Magnus Medical’s online provider directory.

FAQ

Is SAINT a good alternative to antidepressants?

For people living with treatment-resistant depression, SAINT Depression Therapy is an FDA-cleared, non-invasive option that is designed to target the brain’s neural circuitry. Clinical trials show a 79% remission rate after a five-day treatment course.

How is SAINT different from standard TMS?

Standard TMS takes six or more weeks, uses the same brain target for most patients, and studies show remission rates between 17%⁵and 32%⁶. SAINT uses fMRI-guided personalization and an accelerated five-day protocol, achieving 79%² to 90% remission in an average of 2.6 days in clinical trials³.

Who can receive SAINT Depression Therapy?

Adults with major depressive disorder whose symptoms have not improved after at least one antidepressant medication may be eligible for treatment pending a consultation with a Verified SAINT Provider.

Is SAINT safe?

SAINT is non-invasive and has proven generally well-tolerated in clinical trials. The most common side effects are mild to moderate headache or scalp discomfort. It is not recommended for patients with certain metal implants or implanted electronic devices.

Disclaimer: SAINT is a non-invasive, medication-free treatment; however, many patients continue their current prescriptions during and after the 5-day protocol. All care plans should be reviewed and verified by your SAINT provider to ensure optimal treatment safety.

If you are in a crisis, call or text 988 to reach the Suicide & Crisis Lifeline, or chat via 988lifeline.org.

1 Pigott et al. (2023)

2 Cole et al. (2022) 

3 Cole et al (2020)

4 Jensen et al. (2022)

5 Hsu et al. (2019)

6 Blumberger et al. (2018)