Pioneering Single-Day Transcranial Magnetic Stimulation (TMS) Treatment for Depression and Beyond

Introduction

Transcranial Magnetic Stimulation (TMS) has emerged as a transformative treatment for treatment-resistant depression (TRD) and other psychiatric and neurological disorders. With evidence of superior efficacy compared to pharmacotherapy, TMS is now applied to conditions such as anxiety disorders, PTSD, OCD, and even neurological disorders like Parkinson’s and Alzheimer’s diseases. However, conventional TMS protocols require multiple sessions spread over weeks, posing significant logistical challenges for many patients who need to visit our clinical psychologist in New Delhi, Dr. Anuranjan Bist. This has spurred interest in accelerated Transcranial Magnetic Stimulation (TMS) regimens, including a novel single-day protocol, the Optimized Neuroplasticity-Enhanced Depression (ONE-D) regimen.

Barriers to Access and the Case for Accelerated Transcranial Magnetic Stimulation (TMS)

Traditional Transcranial Magnetic Stimulation (TMS) schedules typically involve 20-30 sessions, requiring frequent clinic visits to the Mind Brain Institute or any other clinic that the patient selects. For patients with mobility challenges or those living in remote areas, this can be prohibitive. Accelerated TMS regimens, delivering multiple sessions per day, aim to address this limitation. The ONE-D regimen represents a groundbreaking approach, condensing 20 sessions into a single day while incorporating evidence-based strategies to enhance neuroplasticity and treatment efficacy.

The ONE-D Regimen: Innovations and Optimization

The ONE-D protocol integrates several advancements:

Intermittent Theta-Burst Stimulation (iTBS):

A 3-minute iTBS session replaces the longer 10 Hz sessions previously common, allowing for shorter, effective treatments. Intermittent Theta-Burst Stimulation is a novel development in Transcranial Magnetic Stimulation (TMS) therapy, providing an even more efficient method of treatment. Unlike the conventional 10 Hz sessions that needed to be held for longer periods, iTBS achieves the same therapeutic benefits in just 3 minutes.

This technique applies short, high-frequency bursts of magnetic pulses that are similar to the natural patterns of brain activity, which effectively stimulate neural pathways. By significantly reducing treatment time without compromising efficacy, iTBS has become a game-changer in the field of mental health therapies, making treatment more accessible and convenient for patients. A 3-minute iTBS session replaces the longer 10 Hz sessions previously common, allowing for shorter, effective treatments.

Optimized Session Intervals:

A 30-minute gap between sessions maximizes neuroplasticity, based on preclinical findings. Research indicates that adding a 30-minute break between Transcranial Magnetic Stimulation (TMS) sessions can enhance neuroplasticity to a great extent. This time gap provides the brain with the opportunity to process and consolidate the effects of stimulation, thereby increasing the therapeutic benefits. According to preclinical studies, this method ensures that treatments are not only effective but also optimized for long-term benefits in neural reorganization and recovery.

Pharmacological Augmentation:

The regimen includes d-cycloserine (DCS), an NMDA receptor partial agonist, and lisdexamfetamine, a dopamine precursor, both enhancing neuroplastic effects.

Personalized Targeting:

Using scalp-based heuristics derived from causal network mapping, the regimen ensures precise stimulation of the left dorsolateral prefrontal cortex (DLPFC). To augment the effects of neuroplasticity achieved by Transcranial Magnetic Stimulation (TMS), the combination includes pharmacologic agents like d-cycloserine, an NMDA partial agonist; and lisdexamfetamine, a precursor to dopamine, which increases both glutamate (facilitating the synaptic plasticity) and enhances dopamine levels promoting neural connectivity in the brain, thereby synergistic with Transcranial Magnetic Stimulation (TMS) improving therapeutic outcomes over time.

Study Design and Implementation

A retrospective case series evaluated the ONE-D regimen’s feasibility, safety, and efficacy among 32 patients with unipolar major depression. Patients underwent 20 Transcranial Magnetic Stimulation (TMS) sessions in a single day, supported by DCS and lisdexamfetamine pre-administration. The sessions targeted the left posterior DLPFC using updated localization heuristics, with follow-up assessments conducted over 12 weeks.

Key Findings

Efficacy:

At six weeks post-treatment, 90.3% of patients met response criteria, and 74.2% achieved remission based on the Hamilton Depression Rating Scale (HDRS-17). These results surpassed typical outcomes for standard and accelerated TMS regimens.

Durability:

Improvements were sustained at 12 weeks, with minimal relapse. One patient experiencing partial relapse successfully responded to re-treatment.

Safety and Tolerability:

All patients completed the protocol without serious adverse effects. Common side effects included transient headaches and scalp discomfort, managed with NSAIDs when necessary.

Delayed Onset of Effect:

Unlike pharmacological interventions like ketamine, which provide immediate relief, the ONE-D regimen showed a gradual improvement trajectory, with significant benefits emerging between weeks 1-6 post-treatment.

Broader Implications and Future Directions

The ONE-D regimen demonstrates the potential to revolutionize Transcranial Magnetic Stimulation (TMS) accessibility by overcoming logistical barriers and providing robust, long-lasting relief within a single day. While the delayed response may limit its suitability for acute settings, it is ideal for outpatient care, offering convenience and efficacy.

Optimization and Research Opportunities

Future studies could refine the regimen by exploring:

Simplification of pharmacological augmentation, possibly using alternative neuroplastogens –

Agents such as d-cycloserine (DCS) and lisdexamfetamine are used in pharmacological augmentation to enhance neuroplasticity during Transcranial Magnetic Stimulation (TMS) treatments. However, these drugs have drawbacks, including side effects, cost, and low efficacy in specific patient populations. Future research could focus on the identification of alternative neuroplastogens—compounds that stimulate neural plasticity more efficiently and with fewer drawbacks. Such alternatives could be new synthetic molecules, natural compounds, or even non-invasive biologics that may modulate the brain’s ability to adapt and rewire itself.

Simplifying pharmacological regimens may also make this treatment easier to administer, potentially making Transcranial Magnetic Stimulation (TMS) therapy more widely available. It may be achieved by replacing multigeneric drugs with a singular, highly effective neuroplastogen. A further potential role for personal medicine is through tailoring the pharmacological agent to the unique neurochemical profile of the individual, thus delivering better results in a greater range of patients. This would not only make Transcranial Magnetic Stimulation (TMS) more efficient but also safer and more inclusive.

Shorter inter-session intervals, further reducing treatment duration-

Current Transcranial Magnetic Stimulation (TMS) protocols usually involve a 30-minute gap between sessions to maximize neuroplasticity. This interval, though effective, extends the overall treatment duration, which can be inconvenient for patients with tight schedules. Future studies may investigate whether shorter inter-session intervals, potentially as short as 10 or 15 minutes, can maintain or even enhance treatment efficacy. Such a reduction in time would make Transcranial Magnetic Stimulation (TMS) more practical, especially for patients who need multiple sessions per day.

Furthermore, preclinical evidence suggests that plasticity remains possible even with shorter intervals, by appropriate adjustment of the stimulation protocol. Advanced neurophysiological monitoring could be the basis for real-time adjustments to avoid compromising outcomes by the application of shorter intervals. Taking shorter treatment durations would make the treatment more accessible and more patient-friendly while reducing the entire costs related to longer clinic visitation. The innovation could increase the scalability of TMS as the treatment significantly.

Personalized targeting via advanced imaging techniques for enhanced outcomes –

Current Transcranial Magnetic Stimulation (TMS) targets brain regions based on generalized maps, which may not account for individual variations in brain structure and function. Advanced imaging techniques, such as functional MRI (fMRI) or diffusion tensor imaging (DTI), could enable more precise, personalized targeting of neural circuits. The exact locations of disrupted neural activity could be identified by clinicians to tailor TMS to the specific needs of each patient, maximizing its therapeutic impact.

Personalized targeting also opens the door to treating conditions that are currently difficult to address with Transcranial Magnetic Stimulation (TMS). For instance, advanced imaging could identify subtle abnormalities in less-studied brain regions linked to conditions like PTSD or bipolar disorder. Over time, integrating these imaging techniques into routine practice could make Transcranial Magnetic Stimulation (TMS) not only more effective but also applicable to a broader range of neurological and psychiatric disorders. This level of accuracy could change the face of medicine, setting a new standard in patient care.

Expanding Applications

The success of the ONE-D regimen for TRD paves the way for its application in other conditions, such as chronic pain, Parkinson’s disease, and Alzheimer’s dementia. Additionally, the promising outcomes for a patient with comorbid OCD suggest its potential in broader psychiatric indications.

Limitations

This study’s open-label design and small sample size necessitate further randomized controlled trials. Additionally, the findings may not generalize to more severe cases or inpatient settings.

Conclusion

The ONE-D regimen represents a significant advancement in TMS treatment, offering a practical, effective, and accessible solution for patients facing logistical barriers. They can visit Mind Brain Institute and see Dr. Anuranjan Bist, who would properly guide them, throughout the treatment process. If validated in larger trials, single-day Transcranial Magnetic Stimulation (TMS) protocols could transform care for TRD and other conditions, expanding access and improving outcomes for countless patients.