Objective:

To summarize current knowledge on mechanisms of action of rTMS in bipolar disorder (BD) and identify predictors of treatment response and strategies to enhance therapeutic potential.

Approach:

• Clinical Response Factors: Investigated associations between clinical response to rTMS and factors such as left frontal cortex volume, EEG activity, and default mode network activity.
• Neurochemical Changes: Reviewed evidence of rTMS inducing changes in neurotransmitters and neurochemical substances in BD.
• Targeting Techniques: Explored the potential of neuronavigation and connectivity-guided targeting to enhance rTMS therapeutic outcomes.

Key Findings:

• Lower left frontal cortex volume, slower EEG activity, and lower default mode network activity may correlate with better clinical response to rTMS.
• rTMS can induce neurochemical changes and alterations in EEG patterns in BD, although studies are limited compared to major depressive disorder.
• Navigated rTMS may improve clinical effects and provide insights into therapeutic mechanisms, particularly regarding cognitive performance.

Interpretation:

Several anatomical and neurophysiological factors are associated with therapeutic response to rTMS in BD.

Limitations:

• Available studies on rTMS in BD are limited compared to those in major depressive disorder.
• The understanding of the mechanisms and predictors of response to rTMS in BD remains incomplete.

Conclusion:

rTMS appears to induce significant neurochemical, connectivity, and EEG changes in BD.