When medication alone is not enough, circuit-based treatments such as TMS are reshaping depression treatment. Justin Ray, MSN, PMHNP-BC of South Chesapeake Psychiatry reviews accelerated and theta-burst protocols and what they mean for patients seeking treatment-resistant depression care in Chesapeake, VA and across Hampton Roads.
Circuit Psychiatry: TMS, theta burst, accelerated protocols, and why the delivery system may be the treatment.
Psychiatry has spent most of the modern era organizing treatment around medication. We talk about SSRIs, SNRIs, dopamine partial agonists, NMDA modulation, AMPA throughput, psychoplastogens, neurosteroids, muscarinic signaling, and an expanding list of compounds designed to alter the brain chemically.
But there is another lane in psychiatry that has become too important to treat as peripheral.
Non-pharmacologic treatment is no longer just psychotherapy, exercise, sleep hygiene, or “try this if medications fail.” Increasingly, it includes interventions that directly modulate circuits, alter network activity, change cortical excitability, and in some cases produce response and remission rates that force us to reconsider what we mean by psychiatric treatment in the first place.
Many psychiatric illnesses are not simply disorders of neurotransmitter concentration.
They are disorders of circuit behavior. Major depressive disorder, obsessive-compulsive disorder, ADHD, anxiety, insomnia, trauma-related hyperarousal, and treatment-resistant mood states all involve maladaptive patterns of network activity. Some treatments attempt to change those patterns chemically. Others attempt to change them magnetically, electrically, behaviorally, or through patterned stimulation of neural systems.
The mistake is assuming those categories are separate. A medication may alter receptor signaling and eventually reshape a circuit. A magnetic pulse may alter cortical excitability and eventually reshape synaptic strength. A psychotherapy session may activate a pathological memory network and create the conditions for corrective learning. A neuromodulation protocol may repeatedly stimulate a region until the network begins to behave differently.
Different entry points. Same broader question.
How do we help a dysregulated brain reorganize itself? That question has become one of the central questions in modern psychiatry, whether we are talking about ketamine, esketamine, psychoplastogens, theta burst stimulation, TMS, or emerging device-based interventions. The treatment may look different on the surface, but the deeper goal is increasingly similar: restore adaptive circuit function in a brain that has become stuck.
Transcranial magnetic stimulation, or TMS, is probably the clearest example of this shift. Conventional repetitive TMS uses magnetic pulses to induce electrical activity in targeted cortical regions, most commonly the left dorsolateral prefrontal cortex in major depressive disorder. The clinical rationale is straightforward: depression is not only a serotonin problem. It is also a network problem involving impaired prefrontal regulation, altered limbic reactivity, disrupted reward processing, and reduced cognitive-emotional integration.
This is where the treatment becomes conceptually different from simply adding another medication.
Standard TMS is not trying to flood the synapse with more serotonin. It is attempting to repeatedly engage a regulatory circuit until the network begins to recalibrate. The target is not just the symptom. The target is the circuitry that allows mood, attention, motivation, and emotional regulation to recover.
That distinction matters clinically because conventional TMS protocols usually require daily treatments, five days per week, for four to six weeks. That schedule is not trivial. For clients who work, care for children, live far from a treatment center, struggle with transportation, or have impaired motivation and executive functioning because of the illness itself, the treatment burden can become the barrier.
The science may say “noninvasive.” The real world may say “not accessible.”
The early pivotal depression data were meaningful, but not magical. In the O’Reardon trial, active TMS was superior to sham, with response rates significantly higher across depression scales and remission rates approximately twice as high with active treatment at week six. One report from that trial noted remission of 15.5% at six weeks and 22.6% after the taper phase using HAMD-17 criteria (O’Reardon et al., 2007). A later meta-analysis of high-frequency rTMS trials found response of 29.3% and remission of 18.6% with active treatment compared with 10.4% response and 5% remission with sham (Berlim et al., 2014).
Those numbers may sound modest compared with some modern real-world claims, but they are important because they established that a noninvasive device could meaningfully separate from sham in depression. Since then, clinical practice has often reported stronger outcomes, especially in less restrictive real-world populations and with more refined protocols. Some practical clinical summaries estimate that approximately 50% to 60% of clients with treatment-resistant depression experience meaningful response to TMS, with about 30% to 35% achieving remission, though these estimates vary by population, device, protocol, and prior treatment resistance.
This variability is not unique to TMS.
It is one of psychiatry’s recurring problems. Study design, population selection, symptom severity, placebo response, adherence, endpoint choice, and real-world implementation all shape what we believe a treatment can do. A protocol can look modest in a tightly controlled trial and more impressive in clinical practice. It can also look promising in open-label settings and then shrink under sham-controlled conditions.
Theta burst stimulation changed the access conversation by changing the time burden.
Intermittent theta burst stimulation, or iTBS, delivers patterned bursts intended to induce plasticity-like changes in cortical excitability. The THREE-D trial helped establish that iTBS was noninferior to standard 10 Hz rTMS in depression while dramatically shortening treatment sessions (Blumberger et al., 2018). In practice, that difference is not cosmetic. A treatment session that takes minutes rather than nearly forty minutes changes scheduling, staffing, throughput, and tolerability.
In a clinic, chair time is not a detail. Chair time is access. Theta burst created the foundation for accelerated protocols because if a single session can be delivered in a few minutes, then the next question becomes whether multiple sessions can be delivered in the same day. That question led to some of the most interesting developments in modern interventional psychiatry.
The Stanford Accelerated Intelligent Neuromodulation Therapy protocol, commonly known as SAINT and now often discussed as Stanford Neuromodulation Therapy, pushed this idea forward. Instead of spreading treatment over six weeks, the protocol compresses stimulation into multiple iTBS sessions per day across a five-day course, using individualized targeting informed by functional connectivity. In the sham-controlled trial, remission was reported in 57.1% of participants receiving active treatment compared with 0% receiving sham, with response in 71.4% versus 13.3% (Cole et al., 2022).
That is not just a faster version of TMS.
It is a different treatment philosophy. Conventional TMS asks whether repeated stimulation over weeks can gradually restore prefrontal-limbic regulation. Accelerated personalized TMS asks whether intensive, precisely targeted stimulation can create a rapid circuit state change. The disease process is still major depression, often treatment-resistant depression, but the intervention moves closer to what I would call circuit recalibration.
This is where psychiatry becomes less about medication categories and more about network behavior. But the same clinical excitement that makes SAINT compelling also creates real-world friction. Accelerated personalized protocols often require more infrastructure, more sessions per day, specialized targeting, device availability, and sometimes imaging-based personalization. Insurance coverage does not automatically follow scientific excitement. Conventional TMS for treatment-resistant depression is often covered when criteria are met, but accelerated protocols, SAINT-style delivery, maintenance TMS, single-day models, and off-label targets are frequently not covered or are covered inconsistently.
This is where the payer becomes the third person in the room again.
A protocol can be biologically elegant, evidence-informed, and clinically compelling while still being inaccessible to the person sitting across from you. Science evolves by iteration. Insurance coverage evolves by policy. Those timelines rarely match.
The recent ONE-D case series pushes the access question even further. In that report, investigators described a single-day TMS regimen using 20 iTBS sessions over 9.5 hours, delivered every 30 minutes, paired with off-label pharmacologic augmentation using D-cycloserine and lisdexamfetamine. In 32 adults with unipolar depression, there were no serious adverse events, and week-six HDRS-17 response was 87.5%, with HDRS-17 remission of 71.9%. At week 26, 50% showed sustained remission on HDRS-17 and BDI-II (Vaughn et al., 2025).
Those numbers are hard not to notice.
They also require restraint. This was an open-label case series, not a blinded randomized controlled trial. It included some individuals who had previously responded to TMS, and the protocol combined stimulation with pharmacologic augmentation, making it impossible to know how much of the outcome came from stimulation, how much from D-cycloserine, how much from lisdexamfetamine, how much from patient selection, and how much from nonspecific treatment effects. The authors acknowledged that the observed response trajectory was delayed, building over weeks rather than appearing immediately, which differs from the pattern often seen with ketamine or esketamine (Vaughn et al., 2025).
Still, the concept matters. If replicated under randomized conditions, single-day or highly compressed TMS models could fundamentally change access for clients who cannot realistically attend daily appointments for weeks. That is not merely a convenience issue. It is a health equity issue. A treatment schedule that only works for people with flexible jobs, stable transportation, reliable childcare, and enough executive function to appear in clinic every weekday is already selecting for the people most able to access care.
This is where non-pharmacologic treatment becomes not only a scientific conversation, but a systems conversation.
A six-week protocol and a five-day protocol are not the same intervention in real life, even if both involve stimulation of the dorsolateral prefrontal cortex. The biological target may overlap, but the practical burden does not. In psychiatry, practical burden determines completion.
The D-cycloserine story adds another layer. In a randomized clinical trial of iTBS for major depressive disorder, adjunctive D-cycloserine produced greater improvement than placebo. Response rates were 73.9% with iTBS plus D-cycloserine versus 29.3% with iTBS plus placebo, and remission rates were 39.1% versus 4.2% at four weeks (Cole et al., 2022).
The premise is mechanistically elegant.
If theta burst stimulation depends on NMDA receptor-mediated plasticity, then enhancing NMDA signaling during stimulation may improve treatment effect. This is not simply “TMS plus a pill.” It is stimulation plus plasticity priming. Circuit activation plus synaptic readiness. A device intervention informed by molecular neuroscience.
That is probably where the field is heading. Neuromodulation and pharmacology will become less siloed. We will increasingly ask not only where to stimulate, but what state the brain is in when we stimulate it. We will ask whether medications, sleep, learning, psychotherapy, cognitive engagement, and receptor-level plasticity enhancers influence whether stimulation consolidates into durable improvement.
This same logic is beginning to appear outside depression.
A 2026 sham-controlled crossover trial evaluated iTBS to the left DLPFC in adolescents with ADHD. The study found active iTBS was safe and feasible, with statistically significant improvements in parent-reported working memory, overall ADHD symptoms, anger, depressive symptoms, and anxiety. The effect on core ADHD symptoms was described as medium, while stronger effects were seen in transdiagnostic domains such as working memory, anger, anxiety, and depression (Kavanaugh et al., 2026).
That finding is interesting because ADHD is not merely distractibility. It is a disorder of executive control, working memory, emotional regulation, prefrontal maturation, and network coordination. A DLPFC-targeted intervention may not behave like a stimulant, and it should not be judged as though it is simply another version of stimulant therapy. It may be operating on the organizational architecture beneath the symptom cluster.
That does not mean TMS is ready to become a routine ADHD treatment.
It means we should pay attention. Pediatric and adolescent data remain limited. The study was small. TMS for ADHD remains investigational and off-label. Insurance coverage is unlikely outside research or specialized private-pay settings. A mechanism may make sense, a client may be interested, and a clinician may be intrigued, while the healthcare system still has no practical pathway to deliver or pay for it.
That tension defines much of modern psychiatry. We can often see where the science is going before the system has any pathway to implement it.
The broader implication is that “non-pharmacologic” is becoming an outdated category. It sounds passive, as if these treatments are defined by what they are not. Not medication. Not systemic. Not a pill.
That language undersells what is happening.
These are circuit treatments. Some use magnetic fields. Some use patterned bursts. Some use accelerated dosing schedules. Some use individualized targeting. Some may eventually be paired with pharmacologic plasticity enhancers. Some are clinic-based. Some may become condensed enough to make interventional psychiatry more accessible to people who cannot complete traditional schedules.
The future will likely be less about medication versus neuromodulation and more about sequencing them intelligently.
A client with treatment-resistant depression may need medication to stabilize sleep and anxiety, TMS to improve prefrontal regulation, psychotherapy to consolidate behavioral change, and maintenance strategies to preserve gains. Another client may benefit from accelerated stimulation because a six-week schedule is impossible. Another may eventually receive stimulation paired with a plasticity-enhancing adjunct. Another may not be a candidate at all because the payer will not cover the protocol that best fits the illness.
That is not a side issue.
That is the treatment. Implementation determines whether innovation becomes care. As psychiatry continues moving toward circuit-based treatment, we need to stop treating neuromodulation as an alternative lane. For many clients, it may be the most biologically direct intervention available. It may also be the most operationally difficult to obtain.
That tension is where the next phase of psychiatric care will unfold. The medication era is not ending. It is expanding into a broader model where chemistry, electricity, magnetism, behavior, and plasticity all intersect. The future is not medication versus device. The future is matching the intervention to the circuit, the severity, the timeline, the client’s life, and the system that has to pay for it.
Because in the real world, the best treatment is not only the one that works in a trial, it is the one the client can actually receive, complete, tolerate, and sustain.
Berlim, M. T., Van den Eynde, F., Tovar-Perdomo, S., & Daskalakis, Z. J. (2014). Response, remission and drop-out rates following high-frequency repetitive transcranial magnetic stimulation for treating major depression: A systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. Psychological Medicine, 44(2), 225–239.
Blumberger, D. M., Vila-Rodriguez, F., Thorpe, K. E., Feffer, K., Noda, Y., Giacobbe, P., Knyahnytska, Y., Kennedy, S. H., Lam, R. W., Daskalakis, Z. J., & Downar, J. (2018). Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression: The THREE-D randomized non-inferiority trial. The Lancet, 391(10131), 1683–1692.
Cole, E. J., Phillips, A. L., Bentzley, B. S., Stimpson, K. H., Nejad, R., Barmak, F., Veerapal, C., Khan, N., Cherian, K., Felber, E., Brown, R., Choi, E., King, S., Pankow, H., Espil, F., Pannu, J., Xiao, X., Duvio, D., Solvason, H. B., Hawkins, J., Guerra, A., Jo, B., Raj, K. S., Phillips, M. L., Schatzberg, A. F., & Williams, N. R. (2022). Stanford Neuromodulation Therapy for treatment-resistant depression. American Journal of Psychiatry, 179(2), 132–141.
Cole, J., Sohn, M. N., Harris, A. D., Bray, S. L., Patten, S. B., & McGirr, A. (2022). Efficacy of adjunctive D-cycloserine to intermittent theta-burst stimulation for major depressive disorder: A randomized clinical trial. JAMA Psychiatry, 79(12), 1153–1161. https://doi.org/10.1001/jamapsychiatry.2022.3255
Kavanaugh, B. C., Vigne, M. M., Legere, C., DePamphilis, G., Tirrell, E., Acuff, W. L., Brown, J., Jones, R., Spirito, A., & Carpenter, L. L. (2026). Intermittent theta burst stimulation for attention deficit hyperactivity disorder. Brain Stimulation, 19, 103098.
O’Reardon, J. P., Solvason, H. B., Janicak, P. G., Sampson, S., Isenberg, K. E., Nahas, Z., McDonald, W. M., Avery, D., Fitzgerald, P. B., Loo, C., Demitrack, M. A., George, M. S., & Sackeim, H. A. (2007). Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial. Biological Psychiatry, 62(11), 1208–1216.
Vaughn, D. A., Marino, B., Engelbertson, A., Dojnov, A., Johnson, L., Stine, M., Vila-Rodriguez, F., Weiss, N., Nanos, G., & Downar, J. (2025). Real-world effectiveness of a single-day regimen for transcranial magnetic stimulation using optimized, neuroplasticity-enhanced techniques in depression. Transcranial Magnetic Stimulation, 5, 100200.
South Chesapeake Psychiatry offers psychiatric evaluation and depression treatment in Chesapeake, VA and can discuss whether circuit-based options like TMS fit your care plan, in person or by telepsychiatry across Hampton Roads.
TMS (transcranial magnetic stimulation) uses targeted magnetic pulses to modulate brain circuits involved in depression. It is typically considered for treatment-resistant depression alongside medication management and therapy.
Yes. Many patients begin with virtual psychiatric care in VA to review symptoms and options, then coordinate in-person or clinic-based treatments as needed.
South Chesapeake Psychiatry provides expert psychiatric care and medication management in Chesapeake, VA, with in-person visits and secure telepsychiatry for patients across Hampton Roads and throughout Virginia. To request an appointment for treatment-resistant depression and advanced therapies, contact South Chesapeake Psychiatry today.
To schedule an appointment with South Chesapeake Psychiatry, call 757-908-2124.
This article is for educational purposes only and is not medical advice. Always consult a qualified clinician about your individual care.
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