D-Cycloserine and TMS: A Patient's Guide

Key takeaways

• D-cycloserine (also called DCS) is a medication that was originally invented as an antibiotic, and is now sometimes prescribed alongside alongside transcranial magnetic stimulation (TMS).
• Studies have shown that D-cycloserine might boost neuroplasticity in some circumstances. For that reason, researchers are studying whether or not that property might mean that TMS would work better if combined with D-cycloserine.
• The evidence is promising, but current research is limited and mixed.
• Your TMS provider can help determine whether D-cycloserine is right for you, along with potential benefits, side effects, and costs.

Hearing that D-cycloserine and TMS can work together to ease treatment-resistant depression might give you pause. After all, what does an antibiotic used for tuberculosis have to do with brain health? 

Researchers are studying D-cycloserine (DCS) as an add-on to transcranial magnetic stimulation (TMS) because it acts on a receptor involved in neuroplasticity — the brain’s ability to change and strengthen connections, according to MaryEllen Eller, MD, Radial’s southeast regional medical director. The hope is that DCS could help TMS relieve depression, but the evidence is still emerging. Some clinicians prescribe it off-label, though it isn’t a standard or necessary part of TMS.

Considering another treatment can feel overwhelming, especially when you’ve already tried several. But getting a clearer picture is a good place to start. Below, we’ll explain how it works, what the research says, and how to explore this option with your provider.

What is D-cycloserine, and why is it sometimes paired with TMS?

D-cycloserine is an antibiotic long used to treat tuberculosis. Now, some clinicians prescribe it off-label as an adjunct treatment given alongside TMS to potentially help the brain respond better to treatment.

So why bring an antibiotic into depression care? It turns out, DCS does more than fight bacteria. According to Dr. Eller, it’s a partial NMDA receptor agonist at low doses. That means it influences proteins on brain cells that help them communicate and support learning and memory. These receptors also support neuroplasticity, the brain’s ability to adapt and strengthen connections.

That’s where TMS comes in. TMS treatment stimulates brain circuits involved in mood, which can create lasting mood changes that help relieve conditions like treatment-resistant depression.

“The benefit of TMS is driven by targeted neuroplasticity,” says Dr. Eller. “DCS's potential to promote neuroplasticity led neuromodulation researchers to explore how it could improve TMS outcomes.”

TMS isn’t the first treatment researchers have tried pairing with DCS. Before studying this combination, they explored whether DCS could support exposure therapy for anxiety, according to a meta-analysis published in PLoS One. That earlier work helped build interest in using DCS to strengthen the effects of other mental health treatments like TMS. 

How is D-cycloserine used with TMS?

D-cycloserine is prescribed alongside TMS treatment to potentially support its neurological effects, not as an ongoing, standalone depression medication. When and how often you take the medication depends on your specific TMS protocol. 

Using DCS to enhance TMS is also an off-label use. That means that while DCS is FDA-approved to treat tuberculosis and urinary tract infection, the FDA hasn’t approved it specifically to improve TMS outcomes. Off-label prescribing remains common, and your clinician can explain why they recommend DCS and what evidence supports its use for you.

Research is moving forward, though. In May 2026, the FDA cleared a clinical trial testing NRX-101 — a combination of DCS and the psychiatric medication lurasidone — alongside TMS. That clearance allows researchers to study the approach; it doesn’t mean the FDA has approved it as a treatment. 

It’s also worth checking costs with the clinic and your insurance provider before starting. Even if you have TMS insurance coverage, your plan may not cover the added medication.

What is ONE-D TMS?

ONE-D TMS combines D-cycloserine with 20 short TMS sessions in a single day. Unlike the standard TMS schedule of one session a day over several weeks, this accelerated TMS approach compresses all those visits into one full treatment day.

You take DCS about one hour before starting your TMS sessions, sometimes alongside lisdexamfetamine (Vyvanse), a medication used for ADHD. Then you receive treatments throughout the day, with breaks between sessions. ONE-D uses intermittent theta burst stimulation (iTBS), a form of TMS that delivers magnetic pulses in quick bursts, so each session lasts just a few minutes.

What does the research show so far?

Some studies suggest that adding D-cycloserine to TMS could improve depression symptoms more than TMS alone. Others haven’t found an added benefit.

Here’s what the research shows so far:

Daily TMS

Some of the most promising research about DCS for TMS was published in JAMA Psychiatry. In the study, 50 adults with depression received once-daily iTBS for a month. Some also received DCS for the first two weeks of treatment, while others received a placebo pill. 

After four weeks, the DCS group had better results. Depression symptoms decreased by at least half in about 74% of participants, compared with 29% in the placebo group. And about 39% reached remission (meaning they had few or no remaining depression symptoms), compared with 4% in the placebo group.

Because both groups received the same TMS treatment, this comparison gives researchers a stronger reason to think DCS made a difference. But 50 people is still a very small population to study. Larger trials are needed to confirm the findings and understand who is most likely to benefit.

One-day and accelerated TMS

The research on accelerated treatment is less clear. A 2025 study in Transcranial Magnetic Stimulation followed 32 adults with treatment-resistant depression who received the ONE-D protocol. After six weeks, using various assessments, roughly 87-90% reported a significant drop in symptoms, and between 56-75% reached remission.

Those results are encouraging, but everyone received the same one-day TMS treatment. Without a group receiving TMS alone, researchers can’t tell whether DCS improved the results.

A 2025 study published in Research Square did make that comparison. In the study, 30 participants received 10 iTBS sessions paired with either DCS or placebo. After a week, the DCS group hadn’t improved significantly more than the placebo group. Just note that this research is currently a preprint, meaning it hasn’t yet been peer-reviewed.

The studies used different treatment schedules over different timelines, so comparing them is not apples-to-apples. Regardless, more research is needed to better understand the potential benefits of using DCS alongside accelerated TMS.

Other conditions

Depression isn’t the only condition researchers are studying. A 2025 trial in The American Journal of Psychiatry found that receiving DCS alongside TMS for OCD may help ease symptoms. But the study was small and ended early, so researchers need to confirm the findings.

Researchers have also tested the combination for fibromyalgia. A 2026 study in Neuropsychopharmacology found that adding DCS improved depressive symptoms more than TMS with placebo, but didn’t provide an added benefit for overall fibromyalgia symptoms. 

Finally, DCS has also been studied alongside other mental health treatments like cognitive behavioral therapy for anxiety and PTSD treatment options like exposure therapy, with mixed results. But those studies don’t show whether adding DCS to TMS would help either condition. 

Is D-cycloserine safe to take with TMS?

D-cycloserine used with TMS is generally well-tolerated with no serious adverse events in the daily-TMS trial. Many of the warnings you may see come from its use for tuberculosis, which involves higher doses taken for much longer, Dr. Eller explains. 

“While anything you put into your mouth can cause side effects, a single dose of DCS one hour prior to TMS is not expected to cause significant side effects,” she says.

But that doesn’t mean they can’t happen. Dr. Eller says possible D-cycloserine side effects include:

• Nausea or stomach pain
• Headache
• Dizziness
• Drowsiness

More serious problems, such as confusion, seizures, or changes in mood or behavior, are possible, though Dr. Eller says they’re rare with brief, low-dose use.

Ultimately, whether DCS is a good fit depends on your health history, medications, and treatment plan. Dr. Eller says a history of seizures, psychosis, severe kidney disease, or ongoing alcohol use would make her especially cautious. The prescribing information also lists depression, severe anxiety, and psychosis as reasons not to use DCS, so ask your provider how they weigh that warning when recommending the medication with TMS.

Even though you can receive TMS while on antidepressants, your provider will review your medications to check whether adding DCS is appropriate. They can also talk you through possible DCS and TMS side effects so you feel more prepared and comfortable starting treatment.

Questions to ask your TMS provider about D-cycloserine

If you’re considering TMS and D-cycloserine for depression, you don’t need to arrive at your appointment with all the answers. These questions can help you and your provider talk through whether it makes sense for you:

• Is TMS a good fit for me? Explore whether you’re a good candidate for TMS by asking how your symptoms, past treatments, and medical history shaped the recommendation.
• Which type of TMS would I receive? Clarify whether the plan involves daily visits or an accelerated schedule, and what the treatment days would look like.
• What research supports adding DCS to that approach? Results from one TMS protocol may not apply to another.
• What are the risks for me? Discuss your medications, health history, and any concerns about the prescribing warnings.
• How will we track whether it’s helping? Set expectations for when TMS starts working, how you'll measure symptoms, and who to contact about side effects.
• What does it cost? Ask whether DCS adds to your treatment costs, what insurance may cover, and what you’d pay out of pocket.
• What happens if it doesn’t help? Get a clear explanation of next steps if TMS doesn't work.

You don’t have to decide on the spot or arrive knowing all the science. It’s okay to ask for a clear explanation, take time to think it over, and share your concerns. If you’re unsure where to start, our team can walk you through Radial’s clinical research and TMS therapy at Radial to help you make an informed, confident decision.

The bottom line

If you’ve tried several depression treatments without enough relief, it’s understandable to feel cautious about something new. D-cycloserine is one option researchers are exploring that may help TMS work better. Early results are encouraging, but it’s still being studied and isn’t a required part of TMS treatment.

You don’t have to figure out whether it’s right for you on your own. Your provider can talk through the potential benefits and risks, answer your questions, and help you make the best decision for you.

Frequently asked questions (FAQs)

Does cycloserine affect mental health?

Yes, D-cycloserine can affect mental health because it acts on receptors involved in learning and the brain’s ability to change. These effects could help TMS relieve depression. But DCS could also cause unwanted mood changes, particularly with higher doses used to treat tuberculosis. Tell your provider if you notice new or worsening mental health symptoms.

Do you need D-cycloserine for TMS to work?

No, TMS can relieve depression without D-cycloserine. DCS is an optional, off-label add-on that researchers are still studying, not a required part of treatment.

Can you drink alcohol while taking D-cycloserine?

D-cycloserine can increase  seizure risk, so you should avoid alcohol while taking the medication. Normally it is best to avoid alcohol around the time of a TMS course anyway. Tell your prescriber how much and how often you drink, and ask how long you should avoid alcohol around treatment. 

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