Abstract Background/Aims Fibromyalgia (FM) is a chronic centralised pain disorder affecting 2-4% of the global population, predominantly women. Pharmacological therapies offer only partial relief, with effect sizes rarely exceeding 0.3-0.4 on standardised pain scales, highlighting the need for integrative, non-pharmacological strategies targeting neuroplasticity, lifestyle, and psychosocial mechanisms. To evaluate evidence on non-pharmacological interventions in FM, focusing on efficacy, mechanisms, and patient-centred outcomes related to pain modulation. Methods A systematic review was conducted of clinical trials and meta-analyses published between 2010 and 2025 in PubMed, Cochrane Library, and Embase. Eligible studies assessed interventions including exercise, cognitive-behavioural therapy (CBT), mindfulness-based stress reduction (MBSR), neuromodulation techniques, and lifestyle-based strategies. Outcomes included pain intensity, functional capacity, quality of life, and mechanistic biomarkers (e.g., central sensitisation indices). Results From 2,014 studies screened, 112 met inclusion criteria. Key findings included: 1. Exercise-based interventions: Aerobic and resistance training demonstrated consistent pain reduction (standardised mean difference, SMD = −0.37; 95% CI: −0.48 to − 0.26) and functional improvement. Aquatic exercise yielded additional benefits in adherence and fatigue reduction. 2. Psychological therapies: CBT and MBSR improved pain coping and catastrophising, with pooled effect sizes for pain reduction at − 0.29 (95% CI: −0.39 to − 0.19). Benefits were enhanced when delivered in hybrid (digital + in-person) formats, improving accessibility. 3. Neuromodulation and emerging techniques: Non-invasive brain stimulation (tDCS, rTMS) showed modest analgesic effects (pain reduction of 15-25%) and improvements in cortical excitability indices. 4. Lifestyle and multimodal approaches: Sleep hygiene interventions, dietary modification (e.g., anti-inflammatory diets), and integrative multimodal programmes improved patient-reported global functioning, with long-term adherence emerging as a predictor of sustained benefit. 5. Across modalities, patient engagement and perceived empowerment were consistent mediators of therapeutic response. However, heterogeneity of outcome measures and limited long-term follow-up remain barriers to conclusions. Conclusion Non-pharmacological interventions represent essential, evidence-based strategies for FM management, offering clinically meaningful improvements in pain, function, and quality of life beyond pharmacotherapy. Exercise and CBT remain first-line, while neuromodulation and lifestyle-based therapies are promising adjuncts. Importantly, patient co-design and personalised treatment pathways appear critical to maximising outcomes. Future research should focus on biomarker-driven stratification, scalable delivery models, and longitudinal evaluation to advance precision pain medicine in FM. Disclosure S. Roy: None.
Subham Roy (Wed,) studied this question.