New Pharmacological Perspectives in the Treatment of Fibromyalgia: A Review of Therapeutic Innovations ^†

Introduction: Fibromyalgia is a chronic, multifactorial pain syndrome that is difficult to manage and is characterized by neurochemical changes, dysfunction in pain perception mechanisms, inflammatory factors, and psychosocial aspects. Its pathophysiology involves abnormal modulation of neurotransmitters such as serotonin and noradrenaline, as well as dysfunctions in the neuroimmune axis, resulting in pain amplification and symptoms like fatigue and sleep disturbances. Given the limitations of conventional treatments, new pharmacological approaches have emerged as promising alternatives for individualized management. Accordingly, this review analyzes recent evidence on innovative pharmacological strategies for fibromyalgia, emphasizing their efficacy and safety. Methodology: A review was conducted of articles published between 2021 and 2025 in the PubMed. Twelve studies were selected: one randomized controlled clinical trial that evaluated sublingual cyclobenzaprine and eleven systematic reviews or meta-analyses addressing different pharmacological strategies for the treatment of fibromyalgia. Results: The evidence indicates that duloxetine, pregabalin, and amitriptyline remain the drugs with the strongest scientific support for reducing pain and improving associated symptoms. Sublingual cyclobenzaprine demonstrated significant reduction in pain and improvement in sleep, with an acceptable safety profile. Cannabinoids, particularly cannabidiol (CBD), and low-dose naltrexone show preliminary benefits, including improvement of chronic pain and sleep; however, robust clinical trials are still needed to confirm their long-term efficacy and safety. Conclusions: The findings reinforce the importance of multimodal and personalized therapies that integrate proven drugs, emerging interventions such as cannabinoids, and non-pharmacological strategies, aiming for better pain control, functional improvement, and quality of life in patients with fibromyalgia.