Could One Day of Treatment Be the Answer to Treatment-Resistant Depression?

If you've struggled with depression that hasn't responded to medications, you know the exhaustion that comes with trying yet another treatment—especially when it requires weeks of daily appointments. What if there was a different option?

Understanding TMS: A Proven Treatment for Depression

Transcranial Magnetic Stimulation (TMS) has been transforming lives since it was FDA-approved for depression in 2008. Unlike medications that affect your entire body, TMS uses magnetic pulses—similar to those used in MRI machines—to activate specific areas of the brain involved in mood regulation.

How Does TMS Work?

Think of TMS as a way to "reset" underactive areas of your brain. When you're depressed, certain regions of your prefrontal cortex—the part of your brain responsible for mood, motivation, and emotional regulation—often show reduced activity. TMS uses focused magnetic pulses to stimulate these areas, helping restore normal brain function.

The treatment is:

• Non-invasive (no surgery, no anesthesia)
• Well-tolerated (you're awake and alert during treatment)
• Drug-free (no medications enter your system)
• Effective (recent studies show it's even superior to trying another antidepressant medication)

The Traditional TMS Approach

Conventional rTMS treatment typically involves:

• Coming to a clinic 5 days a week
• Sessions lasting 20-40 minutes each
• Treatment continuing for 4-6 weeks
• A total of 20-30+ sessions

For many people, traditional TMS has been life-changing. Studies show that approximately 50-60% of patients experience significant improvement, with about 30-40% achieving complete remission from depression.

But there's a catch: The weeks of daily appointments create significant barriers. Many patients simply can't commit to this schedule due to distance, work obligations, cost, childcare needs, or mobility challenges.

Enter ONE-D: A Breakthrough Approach

Researchers have developed an innovative protocol called ONE-D (Optimized, Neuroplastogen-Enhanced Depression treatment) that addresses these barriers head-on. The question they asked was simple but profound: What if we could deliver an entire course of TMS treatment in a single day?

What Makes ONE-D Different?

ONE-D combines three evidence-based optimizations:

1. Accelerated Delivery

Instead of spreading treatment over weeks, ONE-D delivers 20 sessions of intermittent theta burst stimulation (a more efficient form of TMS) in one day—one 3-minute session every 30 minutes over a period of 9.5 hours.

2. Enhanced Neuroplasticity

The brain's ability to form new connections—called neuroplasticity—is key to TMS working. ONE-D enhances this with two medications taken before treatment:

• D-cycloserine: A medication that helps strengthen the brain's response to TMS
• Lisdexamfetamine (Vyvanse): A stimulant that research suggests may boost the brain's plastic changes

In our clinic we have had great results with just using the D-cycloserine for plasticity with a patient sample of 8 patients.

If you're concerned about taking a medication you've never heard of, that's completely understandable. Let's talk about D-cycloserine and why the single-dose approach used in ONE-D is particularly safe.

D-cycloserine has been used in medicine for over 50 years, originally developed as an antibiotic for tuberculosis. In recent decades, researchers discovered it also enhances learning and memory formation in the brain—which is exactly what makes it useful for boosting TMS effects.

Here's what makes the ONE-D approach especially safe:

It's just one dose. Unlike daily antidepressants you take indefinitely, or even antibiotics you take for weeks, ONE-D uses a single 125mg dose of d-cycloserine taken once, one hour before your TMS treatment. That's it. You're not starting a new medication regimen or taking pills every day. This one-time use means:

• No long-term side effects given as a single dose
• No need to wean on or off the medication
• No drug interactions with your regular medications (after the treatment day)
• No risk of dependency or tolerance
• Minimal exposure, maximum benefit

The dose is well-studied. The 125mg dose used in ONE-D is actually lower than doses commonly used in other applications. Research has shown that doses ranging from 50mg to 250mg are well-tolerated, and the recent clinical trial that boosted TMS response rates from 29% to 74% used just 100mg—even less than what ONE-D employs.

Side effects are rare. In clinical studies of single-dose d-cycloserine for enhancing brain plasticity, side effects have been minimal. When they do occur, they're typically limited to:

• Mild headache (which is difficult to distinguish from TMS-related headache)
• Slight dizziness
• Mild fatigue

It's been tested specifically with TMS. The groundbreaking 2022 study published in JAMA Psychiatry demonstrated that d-cycloserine combined with TMS was not only more effective than TMS alone, but also safe and well-tolerated. Importantly, there were no serious adverse events related to the medication. [2022 Study Link]

Think of it this way: you're not adding another daily medication to your routine. You're using a single, well-researched dose of a medication that's been safely used for decades, specifically timed to help your brain get the most benefit from TMS treatment. After that single dose is metabolized (within 24 hours), you're done with it—but the enhanced neuroplastic changes it helped create continue working for weeks and months afterward.

3. Optimized Targeting

ONE-D uses a carefully researched target in the left dorsolateral prefrontal cortex—a brain region identified through advanced mapping techniques as particularly important for depression treatment. We go one step further at Cognitive FX, giving our patients an fMRI on site to get the most precise and personalized target possible. We then model our patient's brain and run an electric field (e field) simulation which allows us to not only target the right location but ensure we are getting enough energy into the targets we want.

The Science Behind the Single-Day Approach

You might wonder: can cramming 20 sessions into one day really work as well as spacing them out?

The researchers designed ONE-D based on cutting-edge neuroscience about how the brain forms lasting changes. They discovered that:

• 30-minute intervals between sessions allow the brain to consolidate changes from each treatment
• Neuroplasticity enhancers help the brain retain these changes long after treatment ends
• The combination creates durable improvements that continue developing over weeks

This isn't just theoretical—the results speak for themselves.

The Results Are Compelling

In a recent study, 32 people with medication-resistant depression underwent ONE-D treatment:

Completion and Safety

• All 32 patients completed the full treatment on the same day without serious side effects
• No seizures, no mania, and no treatment-limiting complications
• Average scalp discomfort rated 5.8 out of 10 (similar to traditional rTMS)

Effectiveness for Depression

• 90% showed significant response by 6 weeks post-treatment
• 74% achieved complete remission (essentially symptom-free)
• Depression scores dropped by an average of 75%
• Benefits persisted: At 3 months, 93% maintained their response and 78% remained in remission

Beyond Depression: Anxiety Benefits

For those who also struggled with anxiety:

• 93% response rate for anxiety symptoms
• 77% achieved remission from anxiety
• Average anxiety scores dropped by 79%

The Timeline of Improvement

One of the most interesting—and important—findings is that ONE-D doesn't work instantly. Unlike ketamine, which can provide immediate relief that fades over days, ONE-D works the opposite way:

• Week 1: Minimal improvement (most patients still symptomatic)
• Weeks 2-3: Steady, progressive improvement begins
• Weeks 4-6: Improvement continues and reaches a plateau
• Week 12+: Benefits remain stable

This pattern suggests that ONE-D triggers genuine, lasting changes in brain function rather than providing temporary symptom relief.

With fMRI targeting, we have found that patients respond in a much quicker timeline. Some have seen results as soon as 48 hours after treatment.

Who Are the Ideal Candidates?

ONE-D could be especially beneficial if you:

Face Logistical Barriers

• Live far from TMS centers (rural areas, small towns)
• Have mobility or transportation challenges
• Care for young children or elderly parents
• Can't afford weeks away from work

Have Treatment-Resistant Depression

• Haven't responded to 2+ antidepressant medications
• Experience intolerable side effects from medications
• Want a drug-free treatment option
• Have previously tried traditional TMS with good results but relapsed

Have Comorbid Anxiety

The study showed particularly strong results for those with both depression and anxiety disorders—a common combination that can be especially difficult to treat.

What to Expect on Treatment Day

If you pursue ONE-D treatment at Cognitive FX, here's what a typical day involves:

Day Before Treatment

Arrive at the clinic and spend 45 minutes getting your brain scanned so we have a personalized target based on your brain's specific needs.

Morning (before TMS begins):

• Arrive at the clinic
• Take the D-cycloserine neuroplasticity-enhancing medication (Vyvanse can also be taken if patient wants to take both)
• Complete baseline assessments
• Have your motor threshold determined (this helps set the right stimulation intensity)

Treatment Phase (9.5 hours):

• Receive your first 3-minute TMS session
• Rest for 27 minutes (you're free to read, eat, rest, or walk around)
• Repeat this cycle 19 more times

We have photo biomodulation, cognitive games, and cardio equipment to pass the time.

After Treatment:

• Go home the same day
• Return to normal activities
• Complete a brief check-in (over video call) 6 weeks after treatment
• No additional clinic visits required

Side Effects to Anticipate:

• Scalp discomfort during sessions (manageable with over-the-counter pain relievers)
• Possible mild headache for a few days after treatment
• Temporary jaw discomfort (less common)

The Bigger Picture: Why ONE-D Matters

Depression affects over 280 million people worldwide, and approximately one-third don't respond adequately to first-line treatments. For these individuals, finding effective treatment can feel like an exhausting, never-ending journey.

ONE-D represents a paradigm shift in how we think about brain stimulation therapy. By removing the logistical barriers of traditional TMS while potentially enhancing effectiveness, it could make this life-changing treatment accessible to millions more people.

Beyond Depression

While this study focused on depression, the researchers note that ONE-D principles might extend to other conditions TMS can treat:

• Obsessive-compulsive disorder (OCD)
• Post-traumatic stress disorder (PTSD)
• Chronic pain
• Symptoms of Parkinson's disease
• Certain aspects of Alzheimer's disease

The study even included one additional patient with OCD who experienced dramatic improvement—dropping from severe symptoms to minimal symptoms that remained stable for 3 months.

Important Considerations

While ONE-D shows tremendous promise, it's important to understand:

It's Still Emerging

• ONE-D is not yet FDA-approved as a specific protocol
• It involves "off-label" use of approved components (TMS and medications)
• Not all TMS centers currently offer this approach
• Larger controlled studies are still needed

It Requires the Right Setting

• Treatment must be delivered by experienced TMS providers
• Proper screening is essential to ensure safety
• Medical supervision throughout the day is necessary
• The neuroplasticity-enhancing medications require careful prescribing

Individual Results Vary

• While 90% of study participants responded, 10% did not
• Studies show it can take up to 6 weeks after treatment to experience results
• Insurance coverage varies and may be limited
• Some people may need retreatment if symptoms return

Is ONE-D Right for You?

If you're reading this and thinking "this sounds exactly like what I need," you're not alone. The promise of effective depression treatment in a single day is compelling—especially if you've been struggling for months or years.

Here are some questions to consider:

• Have you tried multiple antidepressant medications without adequate relief?
• Would the logistical burden of 4-6 weeks of daily rTMS visits prevent you from pursuing treatment?
• Are accelerated TMS treatments (like SAINT) too expensive or not covered by your insurance?
• Are you willing to commit one full day to treatment, then wait for 2-6 weeks for the full benefits to develop?
• Do you have realistic expectations that this is not a guaranteed cure, but a highly promising option?
• Are you stable enough to safely pursue outpatient treatment? (ONE-D may not be appropriate for acute suicidal crises requiring inpatient care)

Next Steps

If you're interested in exploring whether ONE-D might be right for you, we encourage you to reach out for a consultation. During this conversation, we can:

• Review your complete treatment history
• Discuss whether you meet the criteria for TMS treatment
• Explain the ONE-D protocol in detail specific to your situation
• Answer all your questions about safety, effectiveness, and logistics
• Discuss costs and insurance coverage options
• Help you make an informed decision about your care

The Bottom Line

Depression is treatable, and advances like ONE-D are expanding what's possible. While no treatment works for everyone, the combination of a 90% response rate and a single-day commitment represents a new and promising option for people who have struggled to find relief.

You don't have to struggle alone, and you don't have to settle for treatments that aren't working. If ONE-D sounds like it might be the breakthrough you've been looking for, we're here to help you explore whether it's the right choice for your unique situation.

Ready to Learn More?

Contact us today to schedule a consultation and discover if ONE-D treatment could be your path to recovery.

Schedule Free Consult Link

Note: ONE-D is an off-label treatment protocol combining FDA-approved TMS with off-label use of medications to enhance neuroplasticity. As with any medical treatment, individual results may vary. This blog post is for informational purposes only and does not constitute medical advice. Always consult with qualified healthcare providers about your specific situation.