Impacto do tratamento farmacológico profilático da migrânea nos marcadores neuroquímicos e inflamatórios : uma revisão sistemática e meta-análise

Abstract

Introduction: Migraine is one of the most prevalent and disabling neurological disorders, characterized by recurrent attacks of severe headache associated with neurological and autonomic symptoms, whose pathophysiology involves activation of the trigeminovascular system, release of pro-inflammatory neuropeptides, and a state of low-grade systemic inflammation in which cytokines and neurogenic mediators play a central role. Objectives: To evaluate, through meta-analysis, the effect of preventive pharmacological treatment of migraine on plasmatic inflammatory biomarkers, including pro-inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), and neuropeptides such as calcitonin gene- related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), among others. METHODS: Systematic searches were conducted in PubMed/MEDLINE and Embase, restricted to publications from January 1, 2014, to December 31, 2024, including randomized clinical trials evaluating adults with migraine (with or without aura, episodic or chronic), diagnosed according to the International Classification of Headache Disorders (ICHD), who received preventive pharmacological treatment recommended by internationally recognized guidelines, with biomarker measurement in both pre- and post-intervention periods; studies using drugs without recognized efficacy for migraine prevention according to evidence-based guidelines were excluded. Quantitative synthesis was possible only for CGRP, assessed in both included studies (total n = 105 participants). The analysis was conducted in RStudio Desktop 4.3.1, using a random-effects model with between-study variance estimated by the DerSimonian–Laird method and confidence intervals adjusted by the Hartung–Knapp– Sidik–Jonkman method, recommended for meta-analyses with few studies (k = 2) as it provides more realistic coverage of the 95% CI and a more conservative control of type I error. Results: The pooled effect for CGRP yielded a mean difference (MD) of −16.47 pg/mL (95% CI: −46.36 to 13.42), which was not statistically significant, with no heterogeneity (I² = 0%); additionally, the study by Dahri et al. reported a significant reduction in TNF-α levels, which was not included in the synthesis due to lack of comparable data. Conclusion: The available evidence, limited and of moderate-to-low methodological quality, does not confirm a consistent effect of preventive pharmacological treatment of migraine on plasmatic inflammatory biomarkers. Larger and methodologically robust randomized controlled trials are needed to clarify the potential anti-inflammatory role of these interventions.