Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder

Abstract

Objective: Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression.

Methods: Ten adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10 Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6-8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5 cm rule and Beam F3 methods.

Results: Seven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5 cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment.

Conclusions: Open-label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted.

Trial registration: ClinicalTrials.gov NCT01502033.

Figures

FIG. 1.

Stealth three-dimensional (3D) rendering of surface fiducial landmarks for a single subject. (A) Coronal view and (B) sagittal oblique view showing the locations of the abductor pollicis brevis (APB) point, the 5 cm rule point (5 cm) rostral/parasagittal from APB, the Beam F3 point (F3), the MRI localized dorsolateral prefrontal cortex (DLPFC) brain target (DBT), and the MRI localized DLPFC scalp target (DST).

FIG. 2.

(A) Coordinates of the dorsolateral prefrontal cortex (DLPFC) scalp target (DST) points (gray circles) in cm from each of the 10 subjects relative to the aligned 5 cm rule point. Note that the majority of DST points are anterior and inferior to the 5 cm rule point. (B) Coordinates of the DST points (black diamonds) relative to the aligned Beam F3 point. Again, the majority of the DST coordinates are anterior and inferior to the F3 point. (C) Coordinates of the 5 cm rule points (gray circles) and Beam F3 points (black diamonds) relative to the aligned DST point. Note that the Beam F3 points are closer to the DST than the 5 cm rule points.