Non-Invasive Electrical Stimulation Combined with Pharmacotherapy for Insomnia: Mechanisms, Clinical Evidence and Drug Development Implications

© 2026 by the Author. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )

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Abstract

Insomnia has become a global public problem, while traditional treatments have obvious drawbacks regarding safety and accessibility. Non-invasive electrical stimulation (NIBS) refers to a class of safe neuromodulation methods for insomnia. This review first illustrates the neurophysiological pathogenesis of insomnia and core stimulation targets, and then reviews the research progress of typical NIBS techniques, including tDCS, tACS and taVNS. We focus on the synergistic mechanisms, clinical effects and economic advantages of NIBS combined with various medications and summarize the practical workflow of combined therapy. Notably, we systematically analyze the implications of this combination paradigm for insomnia drug development, including low-dose formulation design, fixed-dose combination products and companion device development. We also point out the challenges, such as lack of unified parameters and insufficient long-term safety data during clinical translation, and put forward corresponding improvement strategies. In conclusion, NIBS combined with pharmacotherapy is a reliable and promising intervention for insomnia, which provides a new direction for the development of next-generation insomnia therapeutics and deserves further exploration and popularization in clinical practice.

Keywords

Insomnia

Non-invasive electrical stimulation

Combination therapy

Translational medicine

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