Accelerated TMS or accelerated intermittent theta-burst stimulation (aiTBS) is emerging as a promising treatment for those with treatment-resistant bipolar depression. In a recent clinical trial, patients who had not responded to multiple antidepressants showed significant improvements in their symptoms.

Notably, these improvements were seen after just five days of accelerated TMS treatment. With its rapid and non-invasive approach, accelerated TMS could be a solution when traditional therapies have proven ineffective.

What Is Bipolar Depression and Why Is It So Challenging to Treat?

Bipolar disorder (BD) is a chronic mental health condition marked by severe mood swings. These shifts include both depressive and manic episodes. Bipolar depression, the depressive phase, often defines much of the illness’s course.

 According to the World Health Organization (WHO), bipolar disorder affects 2% of the adult population. This makes effective treatment important. Yet, bipolar depression remains notoriously difficult to manage.

Why? Several factors contribute to the treatment challenges:

• Complexity of Symptoms: Patients with bipolar disorder frequently present mixed symptoms, including agitation or irritability, that overlap with depressive features. This symptom overlap often makes diagnosis more challenging. Treatment plans may become more complex.
• Resistance to Antidepressants: Traditional antidepressants, which are effective in major depressive disorder (MDD), can sometimes worsen bipolar symptoms or trigger manic episodes. Patients with treatment-resistant bipolar depression (TRBD) often fail to respond to multiple medication trials, adding to the complexity.
• Risk of Misdiagnosis: Bipolar depression can sometimes be misdiagnosed as unipolar depression due to overlapping symptoms. This can lead to ineffective treatment plans and delays in finding appropriate care.
• Cognitive Impairment: Cognitive dysfunction is common in patients with bipolar disorder during depressive phases. Lack of concentration, memory, and experience of slow thinking are just some of their struggles. Unfortunately, these symptoms often resist typical medications, complicating treatment further.

How Does Transcranial Magnetic Stimulation (TMS) Work?

Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique widely recognized for its effectiveness in treating major depressive disorder (MDD). Recently, TMS has also shown promise in addressing bipolar depression. It works by using electromagnetic fields to stimulate nerve cells in specific brain regions. These regions, particularly the dorsolateral prefrontal cortex (DLPFC), are important for mood regulation.

What Makes Accelerated TMS Different from Traditional TMS?

Accelerated TMS or Accelerated intermittent theta-burst stimulation (aiTBS) and traditional transcranial magnetic stimulation (TMS) both use magnetic pulses to stimulate brain areas related to mood regulation, but they differ in key aspects:

• Speed of Treatment: Accelerated TMS is much faster. Traditional TMS usually requires one session per day over 4-6 weeks. In contrast, accelerated TMS offers up to 10 sessions per day, completed within just 5 days.
• Stimulation Pattern: Accelerated TMS uses a specific burst pattern — 3 pulses at 50 Hz, repeated every 200 ms — that mimics natural brain rhythms, known as theta waves. Traditional TMS delivers a continuous, slower pulse pattern. Difference in pulse structure allows Accelerated TMS to achieve comparable or better effects in a fraction of the time.
• Patient Experience: Accelerated TMS sessions are shorter, lasting just 3 minutes, versus 20-40 minutes for traditional TMS. This reduces the overall time burden for patients without compromising efficacy.

Both options are non-invasive and safe. But, accelerated TMS offers a faster, potentially more efficient alternative.

What Did the Accelerated TMS Study Reveal About Treating Bipolar Depression?

The randomized clinical trial examining accelerated TMS  or accelerated intermittent theta-burst stimulation (aiTBS) for treatment-refractory bipolar depression (TRBD) revealed promising results for this difficult-to-treat condition. Conducted from March 2022 to February 2024, the study focused on 24 individuals with moderate to severe depressive episodes of bipolar disorder (BD). All of whom had failed at least two prior antidepressant treatments. Here’s what the study found:

Significant Reduction in Depression Scores

The primary finding of the study was a substantial reduction in depression scores for participants treated with accelerated TMS compared to those in the sham (placebo) group. All participants were evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS) both before and after treatment.

At baseline, participants in the active accelerated TMS group had a mean MADRS score of 30.4, indicating significant depressive symptoms. After the five-day treatment, their mean score dropped dramatically to 10.5. In contrast, the sham group showed minimal improvement, with scores decreasing only slightly from 28.0 to 25.3.

The estimated difference between the two groups was –14.75, with a confidence interval of –19.73 to –9.77, meaning the difference was statistically significant (P < .001). The Cohen d effect size of –2.19 indicated a large effect, emphasizing the clinical relevance of these results. This suggests that accelerated TMS may be highly effective in reducing depressive symptoms in carefully selected patients with treatment-resistant bipolar depression.

Personalization of Treatment

One of the unique aspects of the study was the personalized approach to targeting brain regions for stimulation. Using resting-state functional magnetic resonance imaging (fMRI), the researchers identified the optimal target in each patient’s brain. The left dorsolateral prefrontal cortex (DLPFC) was selected based on its connectivity to the subgenual anterior cingulate cortex, a region implicated in mood regulation. This precision-guided method likely contributed to the effectiveness of accelerated TMS, as targeting the correct brain regions is critical for maximizing treatment outcomes in neurostimulation therapies.

This personalized approach sets accelerated TMS apart from more generalized treatments and highlights the importance of advanced imaging techniques in optimizing treatment for patients with complex mental health conditions like bipolar disorder.

Accelerated Treatment Schedule

Unlike traditional transcranial magnetic stimulation (TMS), which typically requires daily sessions over four to six weeks, accelerated TMS compresses the treatment into an accelerated five-day schedule. Participants in the study underwent 10 sessions per day, one session every hour, for five consecutive days. Each session delivered 90,000 pulses at 90% of the resting motor threshold. This accelerated approach is particularly appealing for individuals seeking faster symptom relief, as traditional TMS can be time-consuming and difficult to sustain over weeks.

Implications for Clinical Practice

The findings of this study suggest that accelerated TMS could offer a new, effective treatment option for individuals with treatment-resistant bipolar depression, a population that has historically been difficult to treat. The large effect size and rapid symptom reduction observed in this study are highly encouraging, especially given the limited effectiveness of conventional treatments for TRBD. The ability to significantly reduce depressive symptoms in just five days offers hope for individuals who have not responded to other therapies.

However, while the results are promising, the study acknowledges certain limitations. First, the sample size was relatively small, with only 24 participants. Larger studies will be needed to confirm these findings and evaluate the long-term durability of accelerated TMS effects. Additionally, the use of personalized fMRI-guided stimulation may not be feasible in all clinical settings, potentially limiting the widespread application of this approach.

Can Other Mental Health Disorders Benefit from Accelerated TMS?

Accelerated TMS has shown promise beyond bipolar depression. This non-invasive brain stimulation technique may benefit other mental health disorders, particularly those resistant to conventional treatments. 

• Post-Traumatic Stress Disorder (PTSD): Early trials suggest that accelerated TMS could benefit individuals with PTSD. Stimulating the prefrontal cortex, a region implicated in regulating fear and emotional responses, may reduce PTSD symptoms like hypervigilance and anxiety. While more studies are needed, initial findings indicate potential therapeutic value.
• Obsessive-Compulsive Disorder (OCD): ccelerated TMS may also help patients with treatment-resistant OCD. By targeting brain circuits involved in compulsive behaviors and intrusive thoughts, accelerated TMS offers a new avenue for symptom relief. Traditional treatments like medications and cognitive-behavioral therapy can be enhanced with accelerated TMS, potentially improving outcomes.
• Anxiety Disorders: Generalized anxiety disorder (GAD) and panic disorder are other potential candidates for accelerated TMS treatment. Preliminary studies indicate that stimulating areas of the brain responsible for anxiety regulation may reduce symptoms and improve quality of life.

Although research is ongoing, accelerated TMS offers rapid and effective symptom reduction. It’s especially valuable for patients unresponsive to other therapies. This makes accelerated TMS an important tool in psychiatric care.

Why Should You Trust the TMS Institute of Arizona for Your Depression Treatment Needs?

We are leaders in innovative care for depression, offering advanced TMS therapies. Our experienced team creates treatment plans tailored to fit your needs. With modern technology and compassionate support, we’ve helped many overcome treatment-resistant conditions.

Let us help you improve your mental health. Contact us today to schedule a consultation. see how our proven treatments can help you take control of your well-being.

References

Sheline, Y. I., Makhoul, W., Batzdorf, A. S., Nitchie, F. J., Lynch, K. G., Cash, R., & Balderston, N. L. (2024). Accelerated Intermittent Theta-Burst Stimulation and Treatment-Refractory Bipolar Depression. JAMA Psychiatry, 81(9), 936–936. https://doi.org/10.1001/jamapsychiatry.2024.1787

‌ Dembek, C., Mackie, deMauri, Modi, K., Zhu, Y., Niu, X., & Grinnell, T. (2023). The economic and humanistic burden of bipolar disorder in adults in the United States. Annals of General Psychiatry, 22(1). https://doi.org/10.1186/s12991-023-00440-7

‌Bipolar Disorder. (2017). National Institute of Mental Health (NIMH). https://www.nimh.nih.gov/health/statistics/bipolar-disorder

‌Note: Information from this study is provided for general knowledge. Consult a healthcare professional for specific medical advice.