Depression is one of the most common mental health conditions in the world, and for many people, standard treatments like antidepressant medications and talk therapy don’t work. That’s led researchers to develop newer treatments, including transcranial magnetic stimulation, or TMS.
TMS uses magnetic pulses delivered to the scalp to stimulate specific areas of the brain involved in mood regulation. It’s been approved for depression treatment for over a decade and is offered in clinics across the country. A newer, faster version called intermittent theta-burst stimulation (iTBS) can deliver a full treatment session in about three minutes, compared to the 20 to 40 minutes required by older TMS protocols.
At the NY Headache Center, we use TMS off label for migraines, brain fog, long COVID, postconcussion syndrome, and other neurological disorders. The technology has broad potential beyond its original FDA-approved indications.
TMS works, but not for everyone. Roughly half of patients see meaningful improvement, and only about a quarter achieve full remission. Researchers have been looking for ways to boost those numbers. One promising strategy involves pairing TMS with a medication that helps the brain respond more strongly to the stimulation.
The medication is called D-cycloserine, or DCS. It was originally developed in the 1950s to treat tuberculosis, and it’s still used for that purpose today. But at much lower doses than those used for TB, DCS has a different and interesting effect on the brain: it enhances the activity of a receptor called the NMDA receptor, which plays a central role in how the brain forms new connections and adapts to experience. Scientists call this process neuroplasticity.
TMS is thought to work by promoting neuroplasticity in brain circuits that are underactive in depression. The idea behind combining DCS with TMS is that if TMS promotes the formation of new, healthier brain connections, DCS could amplify that process by making the brain’s learning machinery more responsive during stimulation.
In 2022, a team of researchers at the University of Calgary published the first clinical trial testing this combination. They enrolled 50 adults with moderate to severe depression and randomly assigned them to receive either iTBS with DCS (100 mg taken by mouth before each session) or iTBS with a placebo pill. Neither the patients nor the clinicians knew who was getting the real drug.
Patients who received DCS alongside their brain stimulation improved significantly more than those who got the placebo. About 74% of the DCS group responded to treatment, compared to 29% in the placebo group. Remission rates were also much higher: 39% versus just 4%.
No serious side effects occurred in either group. At the low dose used in this study, DCS was well tolerated.
A follow-up study in 2025 looked at how DCS behaves in the body during a course of TMS treatment. That study showed that the amount of DCS in a patient’s bloodstream predicted how much their depression improved. Patients with higher drug levels (within a specific range) got better faster. The researchers also confirmed that taking DCS on weekdays with weekends off prevented the drug from building up to levels that could actually interfere with the treatment.
Getting the timing right also made a difference. In the clinical trial, patients took DCS at least 60 minutes before their TMS session. That’s because the drug needs about an hour to reach effective levels in the bloodstream. Taking it on an empty stomach helps it absorb more predictably; a high-fat meal can significantly delay absorption.
The researchers also chose to limit how long the two treatments were paired. DCS was given only during the first two weeks of a four-week TMS course. The concern was that using it for too long might cause the brain to adapt in ways that would reduce the benefit.
The 2025 follow-up study tested DCS across all four weeks and still saw strong results, with 83% of patients responding and 75% achieving remission. The optimal duration is still being studied.
DCS is FDA-approved and available by prescription, but the commercially available capsule is 250 mg, which is the dose used for tuberculosis treatment. The dose used in the TMS research is only 100 mg. That low-dose capsule needs to be made by a compounding pharmacy.
The same NMDA receptor system that DCS targets is involved in a wide range of neurological conditions, not just depression. NMDA receptors help regulate pain processing, cognitive function, and the brain’s ability to recover from injury. This is one reason TMS itself has shown promise well beyond its original approval for depression OCD, and anxiety.
Research supports the use of TMS for migraine, with clinical trials showing reductions in monthly migraine days and attack frequency. For postconcussion syndrome, pilot studies have demonstrated improvements in headache, mood, and cognitive symptoms like processing speed and verbal fluency following courses of TMS. And for long COVID, early case series have reported improvements in fatigue, brain fog, depression, and even sense of smell after TMS treatment targeting the prefrontal cortex.
At the NY Headache Center, we often see patients who arrive after multiple failed medication trials and are looking for non‑drug options. In our practice, we have seen these benefits in patients with migraines, brain fog, long COVID, postconcussion syndrome, and other neurological conditions. The principle behind adding DCS is the same regardless of the condition being treated: by enhancing the brain’s capacity for neuroplasticity during stimulation, each TMS session may produce a stronger and more lasting effect. While the clinical trial data on DCS specifically paired with TMS comes from depression research, the underlying biology of NMDA-receptor-dependent plasticity applies to other neurological conditions. This makes the DCS-TMS combination a concept worth considering, and we may try it in some of our patients.
This research is still in its early stages. The initial trial was conducted at a single center with 50 participants, and the researchers have been clear that larger, multi-site studies are needed before this approach can be recommended as standard practice.
