A Preliminary Open‐Label Pilot Study of a Pillow‐Based ELF ‐ ELME (Extremely Low‐Frequency, Extremely Low Magnetic Environment) Intervention for Major Depressive Disorder

ABSTRACT Background Mitochondrial dysfunction has been implicated in the pathogenesis of depression. Major depressive disorder (MDD) is a prevalent condition with substantial individual and societal burden. A novel approach—exposure to an extremely low‐frequency, extremely low magnetic environment (ELF‐ELME)—has shown promise. This preliminary study builds on a previous trial using a head‐mounted ELF‐ELME device and explores the potential efficacy and safety of a pillow‐based ELF‐ELME device in patients with MDD. Methods In this preliminary open‐label pilot study, four patients with MDD were treated using a pillow‐based ELF‐ELME device (10 μTesla, 4 ms, 1–8 Hz/8 s) for 2 h daily over 8 weeks. The primary outcome was change in Montgomery–Åsberg Depression Rating Scale (MADRS) scores from baseline to Week 8. Artificial Intelligence‐based MADRS (AI‐MADRS) scores were also assessed. Results Total MADRS scores showed a unidirectional decrease from baseline (33.8 ± 7.3) to Week 8 (21.5 ± 8.7; p = 0.050, FDR = 0.067), and no time point reached statistical significance after FDR correction. In contrast, AI‐MADRS scores significantly decreased from baseline (34.0 ± 8.3) to Week 8 (19.8 ± 6.8; p = 0.040). No serious adverse events were reported. Conclusion These preliminary findings suggest that an 8‐week course of pillow‐based ELF‐ELME intervention may have potential to alleviate depressive symptoms in patients with MDD. However, given the small sample size and open‐label design, the results should be interpreted with caution. Larger controlled studies are warranted to confirm these findings. Trial Registration jRCT number: jRCTs042240061; https://jrct.mhlw.go.jp/en‐latest‐detail/jRCTs042240061