rTMS vs. Antidepressants: A New Path for Treatment-Resistant Depression

Written by Joao L. de Quevedo, MD, PhD

Introduction

For individuals with treatment-resistant depression (TRD)—those who have not found relief with traditional antidepressants—the search for effective treatment options can be frustrating and exhausting. A recent randomized controlled trial by Dalhuisen et al. (2024) explores an alternative: repetitive transcranial magnetic stimulation (rTMS). The study compared rTMS with the next pharmacological treatment step (a switch in antidepressants) and found promising results in favor of rTMS. This blog post will discuss the study’s key findings and their implications for depression treatment.

What Is rTMS?

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation treatment that uses magnetic pulses to stimulate specific brain regions. In treating depression, rTMS is typically applied to the left dorsolateral prefrontal cortex, an area involved in mood regulation. Unlike electroconvulsive therapy (ECT), rTMS does not require anesthesia and is associated with fewer cognitive side effects.

Study Overview

The study by Dalhuisen et al. (2024) investigated the effectiveness of rTMS compared to a switch in antidepressant medication in 89 patients with moderate treatment-resistant depression (i.e., those who had not responded to at least two prior antidepressant treatments). Both groups also received psychotherapy.

Methods:

• rTMS group: Received 25 high-frequency rTMS sessions over 8 weeks targeting the left dorsolateral prefrontal cortex.
• Medication group: Followed the Dutch treatment algorithm, which involved switching to a tricyclic antidepressant or adding augmentation strategies like lithium or an antipsychotic.
• Primary outcome: Changes in Hamilton Depression Rating Scale (HAM-D) scores.
• Secondary outcomes: Response and remission rates, as well as symptom-specific improvements in anhedonia, anxiety, sleep, rumination, and cognitive reactivity.

Key Findings

1. rTMS Outperformed Medication in Reducing Depressive Symptoms

Patients in the rTMS group showed a significantly more significant reduction in depression severity compared to those who switched medications:

• Mean HAM-D score reduction:
  • rTMS: -10.02
  • Medication: -4.19

2. Higher Response and Remission Rates With rTMS

• Response rate (≥50% improvement in symptoms):
  • rTMS: 37.5%
  • Medication: 14.6%
• Remission rate (HAM-D score <8):
  • rTMS: 27.1%
  • Medication: 4.9%

3. Greater Reduction in Anxiety and Anhedonia With rTMS

• rTMS was more effective than antidepressants in improving symptoms of anxiety and anhedonia (loss of pleasure).
• No significant differences were found between the two groups for rumination, cognitive reactivity, or sleep disturbances.

4. Expectations Influence Treatment Outcomes

• Patients’ expectations of treatment correlated with their improvement.
• Those with higher expectations for rTMS tended to experience more significant symptom relief.

Why These Findings Matter

1. rTMS as an Early Treatment Option

Traditionally, rTMS has been considered a later-stage intervention, often used after multiple failed medication attempts. However, these results suggest that rTMS could be introduced earlier in the treatment algorithm—after just two unsuccessful antidepressant trials.

2. Personalized Treatment Approaches

The study highlights that different treatments target different symptom dimensions. For individuals struggling with anhedonia and anxiety, rTMS may be particularly beneficial compared to medication adjustments.

3. The Role of Patient Preferences

Patient preference should be factored into treatment decisions because of the strong correlation between treatment expectations and outcomes. Those open to rTMS may experience better outcomes simply due to higher engagement and optimism.

Limitations and Future Research

• The study only reports short-term (8-week) outcomes; long-term effectiveness remains to be studied.
• While rTMS was superior to a switch in medication, the comparison did not include other augmentation strategies like ketamine or ECT.
• Future research should examine cost-effectiveness and durability of symptom improvement over extended periods.

Conclusion

The findings from Dalhuisen et al. (2024) provide strong evidence that rTMS is more effective than a switch in antidepressants for patients with moderate treatment-resistant depression. With higher response and remission rates, better improvement in anxiety and anhedonia, and a noninvasive nature, rTMS is emerging as a compelling alternative for those struggling with traditional treatments.

As research continues, rTMS could become a more standard, early treatment option for those with depression. If you or a loved one is considering alternatives to medication, discussing rTMS with a mental health professional may be a worthwhile next step.

Reference

Dalhuisen, I., van Oostrom, I., Spijker, J., Wijnen, B., van Exel, E., van Mierlo, H., de Waardt, D., Arns, M., Tendolkar, I., & van Eijndhoven, P. (2024). rTMS as a Next Step in Antidepressant Nonresponders: A Randomized Comparison With Current Antidepressant Treatment Approaches. American Journal of Psychiatry. https://doi.org/10.1176/appi.ajp.20230556

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