Neuromodulation Strategies in Lifelong Bipolar Disorder: A Narrative Review

Abstract

Bipolar disorder is a debilitating psychiatric condition characterized by recurrent episodes of mania and depression, affecting millions worldwide. While pharmacotherapy remains the cornerstone of treatment, a significant proportion of patients exhibit inadequate response or intolerable side effects to conventional medications. In recent years, neuromodulation techniques have emerged as promising adjunctive or alternative treatments for bipolar disorder. We performed a narrative review, according to the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines, to provide a comprehensive overview of the current literature on neuromodulation interventions in bipolar disorder across the course of lifespan. Specifically, it examines the efficacy, safety, and mechanisms of action of various neuromodulation strategies, including, among others, transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), vagus nerve stimulation (VNS), deep brain stimulation (DBS), and it describes the therapeutic experiences across the different ages of illness. Additionally, this review discusses the clinical implications, challenges, and future directions of the integration, in clinical practice, of neuromodulation into the management of bipolar disorder. By synthesizing evidence from different studies, this review aims to inform clinicians, researchers, and stakeholders about the evolving landscape of neuromodulation treatments and their potential role in improving outcomes for individuals with bipolar disorder.

Keywords: DBS; ECT; TMS; VNS; bipolar disorder; neurofeedback; neuromodulation; tDCS.

Figure 1

Differences among the neuromodulation approaches. Note: TMS (Transcranial Magnetic Stimulation); TES (Transcranial Electrical Stimulation); TUS (Transcranial Ultrasound Stimulation); tDCS (Transcranial Direct Current Stimulation); PBM (Photobiomodulation); NF (Neurofeedback); ECT (Electroconvulsive Therapy); DBS (Deep Brain Stimulation); VNS (Vagus Nerve Stimulation); DLPFC (Dorso Lateral Prefrontal Cortex); CCO (Cytochrome C Oxidase); EEG (Electroencephalogram); HPA (Hypothalamus–Pituitary–Adrenal); HPT (Hypothalamus–Pituitary–Thyroid). Level of evidence qualifying studies:—I high-quality, multicenter or single-center, randomized controlled trial with adequate power; or systematic review of these studies;—II lesser-quality, randomized controlled trial; prospective cohort or comparative study; or systematic review of these studies;—III retrospective cohort or comparative study; case–control study; or systematic review of these studies;—IV case series with pre/post-test or only post-test;—V expert opinion developed via consensus process; case report or clinical example; or evidence based on physiology, bench research, or “first principles”.