Clinical effectiveness of pharmacological interventions for managing chronic migraine in adults: a systematic review and network meta-analysis

Abstract

Background Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication is the most effective. We present a network meta-analysis to determine the effectiveness and rank of preventive drugs for chronic migraine in adults. Methods We identified, reviewed, and extracted data from randomised controlled trials (RCTs) of preventive drugs for chronic migraine with at least 200 participants. Data were analysed using network meta-analysis. Findings We included 12 RCTs of six medications (Eptinezumab, Erenumab, Fremanezumab, Galcanezumab, Onabotulinumtoxin A, and Topiramate) compared to placebo or each other. All drugs effectively reduced monthly headache and migraine days compared with placebo. The most effective drug for monthly headache days was Eptinezumab 300mg, with a mean difference of -2.46 days, 95% Credible Interval (CrI): -3.23 to -1.69. On the Surface Under the Cumulative Ranking Area (SUCRA) analysis, the probability that Eptinezumab 300mg was ranked highest was 0.82. For monthly migraine days, the most effective medication was Fremanezumab-monthly, with a mean difference: -2.77 days, 95% CrI: -3.36 to -2.17, and 0.98 probability of being ranked the highest. All included drugs, except Topiramate, improved headache-related quality of life. No eligible studies were identified for the other common preventive oral medications such as Amitriptyline, Candesartan, and Propranolol. The main reasons were that the studies did not define chronic migraine, were undertaken before the definition of chronic migraine, or were too small. Interpretation All six medications were more effective than the placebo on monthly headache and migraine days. The absolute differences in the number of headache/migraine days are, at best, modest. No evidence was found to determine the relative effectiveness of the six included drugs with other oral preventive medications. Registration PROSPERO (number CRD42021265990).

Research priorities for randomised controlled trials in chronic migraine preventive medication: A stakeholder consensus workshop

“…Since each of the drugs work through different pathways it is plausible that more substantial effects could be achieved through combinations. Our literature reviews found modest effect sizes, the smallest being 1.49 fewer monthly migraine days for topiramate, and the largest being 2.77 fewer migraine days per month for Fremanezumab 5 . Effect sizes describe the whole population, including those who did not respond to a medication at all, and so the effect on an individual can be much higher.…”

“…Our 2023 systematic review found that further definitive evidence is needed on many commonly prescribed medications (e.g. amitriptyline, Candesartan, propranolol) [5][6][7] . However, no work exists to guide researchers and funders designing and commissioning research in terms of the priorities of patients and healthcare professionals.…”

Does pain self-efficacy predict, moderate or mediate outcomes in people with chronic headache; an exploratory analysis of the CHESS trial

“…Chronic headache disorders can be profoundly disabling. In comparison to the substantial amount of research on the biological mechanisms of chronic headache disorders, and success in finding drug treatments of proven benefit for chronic migraine [ 1 ], there has been rather less focus on, and less success with, treatments addressing the social and psychological components of the disability caused by chronic headache disorders [ 2 ]. The international classification of headache disorders does not recognise the disorder of ‘chronic headache’ as a distinct disorder.…”

Subarachnoid Hemorrhage Depletes Calcitonin Gene-Related Peptide Levels of Trigeminal Neurons in Rat Dura Mater

“…CGRP is a 37-amino acid peptide expressed in a significant proportion of trigeminal primary sensory neurons; it can be Cells 2024, 13, 653 2 of 18 demonstrated to be present in cerebral and meningeal sensory nerves and is also abundantly expressed throughout the central nervous system [7,8]. Increased levels of CGRP are highly associated with headache disorders such as migraines; the importance of CGRP in pain-related research became obvious following the introduction of CGRP antagonists as antimigraine pharmaceuticals [9,10]. The CGRP-release and the consequent dilation of meningeal and cerebral blood vessels are involved in the regulation of cerebral blood flow, showcasing its importance in certain pathological conditions such as ischemia and SAH [11,12].…”