What to Do When TMS Isn’t Working for Your Patient

By Martha B. Koo, MD, FASAM, FCTMSS, LFAPA, Your Behavioral Health

When a powerful, evidence‑based treatment falls short, the next steps matter even more.

Transcranial magnetic stimulation (TMS) has transformed the treatment landscape for major depressive disorder (MDD). TMS offers, for a majority of appropriately selected patients, meaningful symptom reduction, durable benefit, and the potential for full remission, without the cognitive or systemic side effects associated with electroconvulsive therapy (ECT) and medications. But what happens when TMS doesn’t work?

Despite best efforts, a subset of patients will fail to respond, or will experience only partial relief. This outcome can be devastating-not only for the patient, but also for the clinician- who both believed deeply in the intervention and committed to weeks of treatment. Managing TMS nonresponse requires normalizing expectations, reassessing fundamentals, optimizing protocols, and thoughtfully pivoting when needed.

First, Some Perspective: TMS Works for Most Patients

Across large real‑world registries and clinical trials, TMS produces a clinical response in roughly 60–80% of patients, with remission rates in the range of 30–60%^1,2, depending on patient characteristics, TMS protocols, and outcome measures used. These positive outcomes are particularly notable in patients with treatment‑resistant depression—many of whom have already failed multiple medication trials.

However, not every patient will respond during a standard course of TMS, even when treatment is done “by the book.” When you are caring for that patient, statistics offer little comfort. For both clinician and patient, lack of response can feel personal. Recognizing upfront that nonresponse is a possibility helps frame next steps as a collaborative, clinical problem‑solving situation rather than as a failure.

Setting Expectations Early: Informed Consent Matters

One of the most under-appreciated determinants of how nonresponse is experienced is what the patient was told at the beginning. Informed consent for TMS should cover the likelihood of response and remission, typical timelines for improvement, potential side effects, and alternative or adjunctive treatments to consider in lieu of TMS or if TMS does not work effectively. When patients understand from the outset that TMS is a powerful tool within a broader treatment ecosystem, they are better able to tolerate uncertainty later in the course. Other treatment options to discuss include interventions such as esketamine, medication optimization or augmentation, psychotherapy intensification, vagus nerve stimulation (VNS), and ECT. Discussing these alternative therapies are not meant to undermine confidence in TMS but to reinforce realism, trust, and shared decision‑making.

Understanding the Typical TMS Response Timeline

Before deciding TMS is not working for your patient, it is critical to confirm that enough time and treatment have elapsed. In my experience, after two weeks most patients note subtle improvements- less tearfulness, improved energy, hopefulness and motivation. Often there is a 20-30% reduction in the evidenced- based depression rating scale being used for assessment. Early response, meaning a 50% or more reduction in the rating scale, may be seen at four weeks. Between 4-6 weeks there is clear clinical separation between responders and non-responders. During the taper phase, weeks 6-9, there may be continued gains, especially in slower responders.

Some patients experience a gradual, linear improvement; others report a delayed but meaningful response near the end of the acute course. Premature conclusions, especially before week four, risk abandoning a therapy that may still work.

Recheck the Basics (Before Changing the Plan)

When response is limited, resist the urge to immediately change protocols. Instead, systematically revisit the foundational elements of treatment. Confirm that the patient is taking any prescribed medications consistently and avoiding alcohol and other substances that may blunt neuroplasticity or worsen mood. Assure that the patient, if able, is practicing good sleep hygiene, exercising, and socializing. Rule-out an underlying medical issue that may masquerade as or worsen depression, such as thyroid dysfunction, sleep apnea, anemia, or low testosterone. Rechecking the diagnosis is not backtracking—it is good medicine. Is the patient in psychotherapy? Lack of response to TMS may reflect untreated cognitive, behavioral, or interpersonal drivers that stimulation alone cannot resolve. The combination of TMS and psychotherapy is synergistic. Evidence suggests that patients who are actively engaged in evidence-based therapy during TMS may show a more robust response.³

Confirm That the TMS Is Optimized

Small, technical factors can have major clinical impacts. Recheck the motor threshold. Confirm that coil placement is anatomically accurate and with consistently strong scalp contact. Technique reassessment and MT recalibration are not overkill but sound, quality control.

One of the most consistent findings across the TMS literature is that the more pulses delivered (within safety limits) means more patients ultimately achieve remission. For patients with a partial response, consider extending the acute course. Many insurers will consider course extensions when patients demonstrate at least a 50% reduction in standardized rating scales, ongoing functional impairment, and a trajectory of improvement without full remission. Peer‑to‑peer reviews are often successful when framed around evidence, safety, and long‑term cost‑effectiveness.

Clinical Remission Should Always Be the Goal

Partial response is meaningful, but remission is transformative. Patients who achieve remission show lower recurrence rates, longer durability of benefit, and better functional and occupational outcomes. In contrast, residual symptoms predict recurrence. If a patient is “better but not well,” and cannot undergo a course extension, holding that partial response and revisiting TMS again, around three months later, may still be a reasonable strategy. Patients who are less depressed at baseline are more likely to remit in subsequent courses.

When TMS Isn’t Enough: Thoughtful Next Steps

If optimization fails to produce remission, the treatment journey is not over. Depending on clinical context, next steps may include esketamine, pharmacology, ECT, VNS, or emerging neuromodulation strategies. The key is intentional sequencing rather than reflexive switching.

A Final Word: Nonresponse Is Not Failure

Non-response is not a reflection of inadequate care or poor judgment. It is an inherent reality when treating complex, heterogeneous neuropsychiatric illness. What matters most is not whether the first intervention succeeds, but how thoughtfully and collaboratively you respond when it does not. By reassessing fundamentals, optimizing technique, aiming for remission, and maintaining a collaborative, informed relationship with the patient, clinicians can turn a moment of disappointment into a pivot point that may ultimately lead to full recovery.

References

Csukly G et al (2025). Response prediction for repetitive transcranial magnetic stimulation treatment. Curr Opin Psychiatry. 38(5):334-340. https://pubmed.ncbi.nlm.nih.gov/40709628/
Sackeim, HA et al (2020). Clinical outcomes in a large registry of patients with major depressive disorder treated with Transcranial Magnetic Stimulation. J. of Affective Disorders, 277: 65-74.https://doi.org/10.1016/j.jad.2020.08.005.
Donse, L et al (2018). Simultaneous rTMS and psychotherapy in major depressive disorder: Clinical outcomes and predictors from a large naturalistic study. Brain Stimulation, 11( 2): 337-345. https://doi.org/10.1016/j.brs.2017.11.004.