Neuromodulation to Promote Recovery Following Traumatic Brain Injury: A Narrative Review of Current Pharmacologic and Non-Pharmacologic Approaches

Traumatic brain injury (TBI) is a leading cause of long-term neurological disability worldwide and is frequently associated with persistent impairments in consciousness, cognition, mood, and functional independence. Despite advances in acute neurocritical care, effective therapies that enhance neurological recovery remain limited. Neuromodulation has emerged as a promising strategy to augment neuroplasticity and improve recovery through both pharmacologic and non-pharmacologic approaches. This narrative review summarizes current evidence supporting pharmacologic neuromodulatory therapies, including central nervous system stimulants (methylphenidate and modafinil), dopaminergic agents (amantadine and bromocriptine), acetylcholinesterase inhibitors (donepezil and rivastigmine), and selective serotonin reuptake inhibitors (sertraline and fluoxetine). Mechanisms of action, clinical efficacy, adverse effects, and practical considerations across the acute, subacute, and chronic phases of TBI recovery are discussed. Emerging non-pharmacologic neuromodulation techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation, are also reviewed. Although amantadine remains the only neuromodulator supported by moderate-quality guideline recommendations for accelerating recovery in disorders of consciousness, accumulating evidence suggests that several additional pharmacologic and non-pharmacologic neuromodulation interventions may improve attention, executive function, fatigue, mood, and rehabilitation participation in carefully selected patients. However, current evidence is limited by heterogeneous study populations, small sample sizes, inconsistent outcome measures, and a paucity of long-term randomized controlled trials. Future research should prioritize adequately powered comparative studies, standardized outcome measures, biomarker-guided patient selection, and multimodal treatment strategies to optimize neurological recovery following TBI.