The SAINT protocol (Stanford Accelerated Intelligent Neuromodulation Therapy) is currently the TMS protocol with the highest remission rate in a controlled trial for treatment-resistant depression: 78.6% in five days. But it is not the right fit for everyone, and other protocols, including Deep TMS, iTBS, and standard rTMS, carry different evidence profiles suited to different severity levels.
Not every TMS protocol works the same way for severe treatment-resistant depression (TRD). A person who has tried six or more medications without lasting relief faces a different clinical reality than someone earlier in their treatment journey. The protocol matters as much as the decision to try TMS in the first place.
This guide ranks the leading TMS protocols by their evidence for severe TRD, explains how severity profiles map to protocol selection, and walks through how a severity-matched approach works in practice.
What is the SAINT protocol for TMS?
SAINT stands for Stanford Accelerated Intelligent Neuromodulation Therapy. Developed by Dr. Nolan Williams and his team at Stanford University, it compresses a full course of TMS into five days instead of the standard six weeks.
Three features set SAINT apart from conventional TMS:
- It uses functional MRI (fMRI) to locate the exact brain region to target for each person, rather than relying on manual measurement
- It delivers treatment through intermittent theta burst stimulation (iTBS), a pulse pattern that mimics the brain’s natural rhythms in 10-minute sessions
- It provides 10 sessions per day over five days, totaling 90,000 pulses (compared to roughly 54,000 in a typical standard six-week course, though exact pulse counts vary by protocol)
The speed matters for people in crisis. Someone experiencing suicidal ideation or occupational collapse from severe depression cannot always wait four to six weeks for a standard course to take effect. SAINT was designed specifically to close that gap.
In a double-blind, sham-controlled trial by Cole, Phillips, Bentzley et al., published in the American Journal of Psychiatry (2022), 78.6% of participants with treatment-resistant depression achieved remission after five days of active SAINT treatment, compared to 13.3% in the sham group. Dr. Nicholas Trapp at the University of Iowa, one of the first academic centers to offer SAINT (2025), reported that early real-world data suggests up to 80% of patients experience remission, with effects often lasting months.
SAINT received FDA clearance through Magnus Medical, which licensed the technology from Stanford. It is not yet widely covered by insurance, and availability remains limited to select academic medical centers and specialized clinics.
Evidence-ranked TMS protocols for severe TRD
Different protocols carry different levels of evidence for people with severe, medication-resistant depression. Here is how they compare:
| Protocol | Response Rate | Remission Rate | Treatment Timeline | Best Evidence For |
|---|---|---|---|---|
| SAINT (SNT) | NR (see remission) | ~79% (RCT, n=29) | 5 days | Severe TRD, rapid intervention, crisis situations |
| Deep TMS (BrainsWay) | 70-80% (real-world) | 32.6% (RCT); up to ~60% in real-world extended courses | 4-6 weeks | Moderate-to-severe TRD, multiple comorbidities |
| iTBS (standard) | 45-55% | 29-33% | 2-4 weeks | Moderate TRD, older adults, time-constrained schedules |
| Standard rTMS | 50-60% | 30-40% | 6 weeks | Moderate TRD, broadest insurance coverage |
NR = not separately reported in the primary sham-controlled trial. The 78.6% remission rate is from Cole, Phillips, Bentzley et al. (2022). Response rate (50%+ symptom reduction) was not reported independently.
SAINT: highest remission rate in a controlled trial
The data from Stanford’s sham-controlled trial is striking: a 78.6% remission rate exceeds what any other TMS protocol has achieved in a controlled study. However, the trial was small (29 participants at the planned interim analysis), and large-scale independent replication is still underway. Early real-world data, including reports from the University of Iowa’s program, suggests similar efficacy, but the evidence base is young compared to standard rTMS and Deep TMS, which have been validated across thousands of patients in multiple independent trials.
A 2025 durability study by Geoly, Williams et al., published in Brain Stimulation, found that a subset of participants remained in remission at 12 weeks after a single course. A separate preliminary study by Stimpson, Ford et al. (2025) on personalized continuation therapy followed 21 participants for 12 months and found that proactive retreatment triggered by early symptom recurrence helped maintain low depression severity scores over the follow-up period. Larger controlled trials are needed to confirm these maintenance findings.
The precision targeting is part of what drives these results. Standard TMS places the magnetic coil based on a general anatomical estimate. SAINT uses each person’s fMRI scan to identify the specific area of the left dorsolateral prefrontal cortex (DLPFC) most functionally connected to the subgenual anterior cingulate cortex, a region implicated in depression.
Deep TMS (BrainsWay): broader reach, FDA-cleared
Deep TMS uses a specialized H-coil that stimulates deeper and broader brain regions than the standard figure-8 coil. While standard rTMS reaches the superficial dorsolateral prefrontal cortex, deep TMS can reach the ventral lateral and ventral medial prefrontal cortex, areas involved in emotional regulation in severe depression.
BrainsWay’s pivotal multicenter randomized controlled trial, published in World Psychiatry (2015), found response rates of 38.4% vs. 21.4% for sham, and remission rates of 32.6% vs. 14.6% for sham, among patients who had failed one to four prior antidepressant trials. A 2024 phase IV study on late-life depression found that response rates reached approximately 70% after 20 sessions and 80% after 30 sessions among 247 older adults in real-world settings. Remission rates in that study approached 60% after 30 sessions, though this was an open-label study in a specific population, representing a different level of evidence than the pivotal RCT.
Deep TMS holds full FDA clearance for major depressive disorder and OCD, giving it the strongest regulatory standing among advanced TMS options.
iTBS: shorter sessions, evidence in older adults
Intermittent theta burst stimulation delivers the same pulse pattern used in SAINT but without the accelerated five-day schedule or fMRI-guided targeting. Each session takes about three minutes (compared to 37 minutes for standard rTMS), making it practical for people who struggle with longer sessions.
Emerging evidence suggests iTBS may offer advantages for older adults with TRD, though head-to-head comparisons with standard rTMS in this population are still limited. A network meta-analysis published in Molecular Psychiatry(2024) concluded that iTBS applied to the left DLPFC had a favorable risk-benefit balance compared to other theta burst stimulation protocols. [Note to publisher: add hyperlink to the Molecular Psychiatry 2024 meta-analysis once DOI is confirmed.] The THREE-D trial, which compared iTBS to standard rTMS across a broader population, found iTBS to be non-inferior, with some evidence suggesting advantages in specific subgroups.
Standard rTMS: established safety, broadest access
Standard rTMS has the longest safety record and the most insurance coverage of any TMS protocol. Response rates of 50-60% and remission rates of 30-40% are well-documented across multiple meta-analyses. For someone with moderate TRD and good insurance coverage, standard rTMS is often the most accessible starting point.
The trade-off is time: 30-36 sessions over six weeks. For people managing severe depression alongside work, caregiving, or other responsibilities, this timeline can be difficult to sustain. And for those with five or more medication failures, the evidence favors more intensive protocols.
Which protocol fits your severity profile
Protocol selection should follow from clinical evidence matched to individual circumstances, not from whatever a clinic happens to offer. Here is how severity profiles typically map to protocol recommendations:
SAINT may be recommended when:
- Depression severity scores are high (such as a Hamilton Depression Rating Scale score of 25 or above, indicating very severe depression)
- Five or more medications have been tried without adequate response
- Suicidal ideation requires rapid intervention
- Occupational or social crisis makes a six-week timeline impractical
Deep TMS may be recommended when:
- Moderate-to-severe TRD is present alongside multiple comorbidities
- The person has not responded to standard rTMS
- Research-backed bilateral stimulation and deeper brain targeting are clinically appropriate
iTBS may be recommended when:
- The person is an older adult with TRD
- Shorter session times improve tolerability or adherence
- Depression severity is moderate rather than severe
Standard rTMS may be recommended when:
- TRD is moderate and fewer than five medications have been tried
- Insurance coverage is a primary consideration
- Long-term safety data is a priority for the person’s decision-making
How a severity-matched protocol approach works
Many clinics offer one or two TMS protocol options. A severity-matched approach works differently. It starts with a thorough assessment and matches protocol to the individual’s clinical profile based on the evidence reviewed above. While no published studies have compared outcomes between severity-matched and standard protocol selection, the clinical rationale is grounded in the varying evidence bases described above.
At Nushama, the workflow follows this sequence:
- Psychiatric severity assessment using validated scales (such as the HAM-D) to establish a baseline and quantify depression severity
- Treatment history review documenting medication failures, prior TMS or ECT experience, and comorbid conditions
- Protocol selection guided by evidence: SAINT for the most severe and time-sensitive cases, deep TMS for members needing broader neural stimulation, iTBS or standard rTMS for moderate profiles
- Outcome tracking through weekly symptom scores and cognitive assessment during treatment
- Protocol adjustment if response is inadequate by week three, rather than continuing the same approach
- Maintenance planning tailored to the individual, because relapse prevention requires its own strategy
This process means the recommendation changes based on your specific profile. A person with a HAM-D score of 28 (very severe depression) and seven medication failures gets a different plan than someone with a score of 18 (moderate depression) and two failures.
If you are living with treatment-resistant depression and exploring TMS options, Nushama’s care team can help determine which protocol matches your clinical picture. Speak with our care team to start with a consultation.
For more background, see our guides on how TMS therapy works for depression, accelerated TMS protocols, or the broader landscape of alternative treatments for depression.
FAQs
How long do the results of the SAINT protocol last?
In the Stanford controlled trial, 78.6% of participants achieved remission, and a 2025 durability study by Geoly and Williams found that some participants maintained remission at 12 weeks after a single course. A separate preliminary study on personalized continuation therapy suggested that proactive retreatment may help sustain remission over 12 months, though larger trials are needed to confirm this.
Is SAINT covered by insurance?
Most insurance plans do not yet cover SAINT, since it uses newer fMRI-guided targeting and an accelerated schedule that fall outside standard coverage policies. Standard rTMS has the broadest insurance coverage among TMS options.
What is the difference between deep TMS and standard TMS?
Deep TMS uses a specialized H-coil that reaches deeper brain structures (including the ventral prefrontal cortex) than the standard figure-8 coil. Standard TMS stimulates the more superficial dorsolateral prefrontal cortex. For severe TRD, the ability to reach deeper circuits may improve outcomes, though both are FDA-cleared for depression.
Can TMS be combined with ketamine therapy?
Some people benefit from combining TMS with other treatments, including ketamine-assisted therapy. A care team can help determine whether a combined approach is appropriate based on your treatment history and goals.
