If you’ve been through a course of TMS, or ketamine, and you still don’t feel better — this page is for you.
That experience is more common than most patients realize. A 2023 peer-reviewed review published in Frontiers in Neuroscience (Debowska et al.) found that while TMS is effective in 30 to 90% of treatment-resistant depression patients depending on the protocol used, and ketamine is effective in up to 70% — roughly 30% of patients still do not respond to ketamine alone. The question isn’t whether you failed the treatment. The question is whether a different approach — or a combination — might work where a single method couldn’t.
At Interventional Psychiatry of Philadelphia, we offer ketamine and TMS combination therapy for patients with treatment-resistant depression. Here is what that means, why it makes scientific sense, and what the evidence shows.
Ketamine and TMS combination therapy for treatment-resistant depression involves delivering intravenous ketamine infusions and repetitive transcranial magnetic stimulation either concurrently or in a coordinated sequence, with the goal of producing greater and more durable antidepressant effects than either treatment achieves on its own.
The rationale is not simply “more is better.” TMS and ketamine act on the brain through different but overlapping pathways — and those pathways may reinforce each other.
For more on how each treatment works individually, see our TMS Philadelphia page and our Ketamine Philadelphia page
TMS and ketamine approach depression from different angles, and that difference matters clinically.
Ketamine provides relief within hours to days through the glutamate system. TMS takes three to six weeks to show results but produces more durable changes in the circuits involved in mood regulation. Used together, they may address what neither resolves alone — ketamine providing rapid relief while TMS builds the sustained circuit-level change.
At the molecular level, the Debowska et al. review identified a key mechanism: both treatments increase glutamate signaling, both activate AMPA receptors, and both raise BDNF — the molecular driver of neuroplasticity. The authors described the two treatments as acting in a potentially synergistic manner, meaning their combined effects may be greater than the sum of each used separately.
There is also a timing hypothesis with practical clinical implications. Ketamine appears to open a window of heightened neuroplasticity that can last up to a few days. Within that broader window, we believe the optimal sequencing is much tighter, delivering TMS within about 30 minutes of the ketamine infusion, to help the brain consolidate the changes TMS is designed to drive.
The Debowska et al. review examined 11 published studies of combined TMS and ketamine for treatment-resistant depression — mostly small case studies and case series, with one retrospective study of 28 patients and one of 21. Results across these studies were generally positive: patients showed substantial symptom reduction, and some achieved full remission. The authors noted that combination therapy showed higher efficacy compared to either treatment used alone across the studies reviewed.
Adverse effects were generally mild and transient, with no severe adverse events reported. The review also addressed a theoretical safety concern — that ketamine could increase motor cortex excitability when paired with excitatory rTMS — but noted this has not been observed in the prefrontal cortex, which is the region targeted for depression treatment.
It is worth being direct about the state of the evidence: the Debowska et al. review was clear that no randomized controlled trials of ketamine and TMS combination exist yet, protocols vary widely across the studies reviewed, and the evidence base is preliminary. The research is encouraging and growing — it is not a finished story. Patients should weigh this honestly when considering the option.
For patients who feel they have exhausted their options, one published case report is worth knowing about. A patient was referred for combination treatment after failure to respond to first- and second-line pharmacotherapy and psychotherapy. After minimal response to both rTMS and ketamine when used individually, a combination rTMS and ketamine protocol led to complete and sustained remission. A single case is not clinical evidence — but it illustrates the clinical logic for trying the combination when individual treatments have not succeeded.
This practice is structured specifically to offer combination protocols. Not all practices that offer TMS also offer ketamine, and fewer still coordinate both as an integrated treatment plan under the care of a single treating clinician. We do and have successfully performed this treatment many times.
Combination treatment is worth discussing if you:
It is not automatically the right choice for every patient, and it is not a first-line treatment. The right answer depends on your history, severity, and what you’ve already tried.
A combination protocol is developed individually based on your clinical history. The general approach involves scheduling ketamine infusions and TMS sessions in close sequence, with TMS delivered within about 30 minutes of the ketamine infusion to align with the period when the brain’s response to ketamine is most active. This is not something that can be replicated by receiving the two treatments on different days or at different locations.
This combination is office-based. You don’t need to be hospitalized, and you can generally maintain your normal routine during treatment. Sessions are monitored throughout, and your clinician will adjust the protocol based on how you’re responding.
Non-response to one treatment — or even both separately — does not mean combination therapy won’t work. The Debowska et al. review, which examined 11 studies of combined rTMS and ketamine, found that patients who had not responded to either treatment individually achieved positive outcomes when the combination was used. The mechanisms differ enough that prior non-response does not rule out a response to the combination. This should be discussed directly with a clinician who can review your specific history.
Ketamine and TMS combination therapy coordinates intravenous ketamine infusions with TMS sessions, typically timing the TMS to begin within about 30 minutes of the ketamine infusion, during the period when the brain’s response to ketamine is most elevated. Ketamine rapidly shifts the brain’s glutamate system, activating AMPA receptors and raising BDNF levels. TMS applies targeted magnetic stimulation to the left dorsolateral prefrontal cortex. Together, they promote complementary circuit-level changes that neither produces as reliably on its own.
Adverse effects in the studies reviewed by Debowska et al. were generally mild and transient, with no severe adverse events reported. The theoretical concern about ketamine increasing cortical excitability when combined with excitatory rTMS has not been observed in the prefrontal cortex specifically. Combination treatment requires careful clinical oversight, which is why it is offered in a monitored, office-based setting by a treating clinician.
Yes. Combination ketamine and TMS therapy is available at Interventional Psychiatry of Philadelphia, 2401 Pennsylvania Ave, Suite 1C44-45, Philadelphia, PA 19130.
The difference is coordination. When TMS and ketamine are offered in the same practice, the treating clinician can schedule them in a deliberate sequence — timing TMS sessions to coincide with the neuroplasticity window ketamine opens, monitoring how you respond to each, and adjusting the protocol accordingly. Simply receiving both treatments in the same building from separate providers without a shared protocol is not the same thing.
A consultation. We’ll review your treatment history, discuss your goals, and determine whether combination treatment is appropriate — and if so, what the protocol should look like for you.
If you’ve already tried TMS or ketamine without full relief, combination treatment exists precisely for patients in this situation.
Call 215-222-0310 or request a consultation online. We see patients from Philadelphia and the surrounding area, including Center City, Fairmount, Fishtown, Northern Liberties, South Philadelphia, West Philadelphia, and the broader Delaware Valley.
