Peripheral nerve block in patients with medication-overuse headache: systematic review and meta-analysis

Background: Medication-overuse headache (MOH) is a disabling condition, particularly in settings with limited access to advanced preventive therapies. Peripheral nerve blocks (PNB) may offer a pragmatic option to reduce headache burden during MOH management. We aimed to assess the efficacy and safety of PNB in adults with MOH. Methods: We conducted a systematic review in January 2025 using Scopus, PubMed, Embase, Web of Science, and the Cochrane Library. Randomized clinical trials comparing PNB with standard of care or other active interventions in adults with MOH were eligible. Primary outcomes included headache frequency, headache intensity, successful detoxification, and adverse effects. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2.0. Random-effects meta-analyses were conducted when appropriate, and certainty of evidence was evaluated using the GRADE approach. Results: Three randomized clinical trials involving 249 adults with MOH were included. All trials evaluated bilateral greater occipital nerve blocks, with variability in anesthetic agents, number of sessions, and use of additional nerve block sites. Standard of care consisted of medication withdrawal, hydration, and preventive therapy. Follow-up ranged from 1 to 4 months. Compared with standard of care alone, a single PNB session significantly reduced headache frequency (–4.56 days/month; 95%CI: − 7.46 to − 1.66) and monthly rescue medication use (–2.30 doses of medication/month; 95%CI: − 2.71 to − 1.89), without significant effects on headache intensity or detoxification success. Multiple PNB sessions were associated with greater reductions in headache frequency (–9.00 days/month; 95%CI: − 9.45 to − 8.55), headache intensity (–2.65 units in visual analog scale; 95%CI: − 2.77 to − 2.53), and monthly rescue medication use (–6.70 doses of medication/month; 95%CI: − 7.10 to − 6.30), with low to moderate certainty of evidence. Compared with topiramate, a single PNB session did not reduce headache frequency (+ 1.50 days/month; 95%CI: +1.21 to + 1.79), with no differences in headache intensity (very low certainty). Adverse effects were only reported by one trial, with no significant differences compared with topiramate. Conclusion: PNB, particularly when administered in multiple sessions, may reduce headache frequency and intensity in adults with MOH when other therapies are unavailable. However, given the limited evidence and low certainty, further high-quality trials are needed to define optimal protocols and long-term effectiveness and safety.