Heidi Moawad, MD
With increasing options for migraine therapy, the right choice for each patient might not be clear. And many individual patients could experience relief from any of the different choices, meaning that there is often more than one “right” answer when it comes to selecting a migraine treatment approach for each patient. Triptans and nonsteroidal anti-inflammatory drugs (NSAIDs), which have been around for decades, have shown consistent success in treating migraine episodes. Newer therapies could be safer for patients who have contraindications to triptans or NSAIDs, and these newer medications could be more effective for some patients, but we are still trying to fully understand which types of patients. Studies aimed at reaching conclusions regarding comparisons between triptans, calcitonin gene-related peptide inhibitors (CGRPi), and other treatments can help us determine which of the different categories of treatments are most effective for certain migraine populations (age or migraine subtype) or indications (acute vs preventive therapy).
A review published in 2023 in Aging and Disease described several markers of aging that are associated with migraine, including epigenetic aging and oxidative stress. 2 The review authors noted that markers of cellular senescence (ie, irreversible inhibition of cellular division) were increased in association with migraine. Additionally, endothelial progenitor cells, which reflect an increased ability for cell renewal, were decreased among migraine patients compared with the control group.
Telomeres, composed of nucleotides, are part of chromosome structures, serving to protect the molecular integrity of DNA. It has been established that shortened telomeres, often considered a reflection of aging and a marker of high potential for genetic and cellular damage, are a risk factor for physiologic changes that occur with the aging process. The 2024 Scientific Reports cross-sectional study included data from 6169 participants in the National Health and Nutrition Survey (NHANES) from 1999 to 2002. 1 The researchers used statistical analysis to determine whether there was an age-influenced telomere length in relation to migraine. They found that “telomere length was inversely associated with migraine risk in those aged 20-50 years, while no relationship was observed in those aged > 50 years.” The significance of this association among the younger group, but not among the older group, is not clear.
The limited research regarding the links between migraine and physiologic markers of aging has not untangled cause-and-effect distinctions. And while there is no evidence that preventing or treating migraine could slow down these pro-aging molecular processes, we do know that the distress of migraine episodes contributes to pain, anxiety, stress, depression, and sleep disruption. Given that we can’t change a patient’s hereditary predisposition to migraines, we can make an effort to alleviate the impact of migraine by using the tools that we have.
An article published in September 2024 in the BMJ described the results of a meta-analysis that included “137 randomized controlled trials with 89,445 participants allocated to 1 of 17 active interventions or placebo.” 3 Treatments included NSAIDs, paracetamol, triptans, and CGRPi. The authors observed that triptans “had the best profiles and were more efficacious” than other treatment categories, including CGRPi. Interestingly, they observed that eletriptan and ibuprofen performed better for sustained pain freedom. Efficacy and sustained relief are crucial for patients with migraine, and for those who experience relief with simple over-the-counter ibuprofen, it makes sense to avoid making changes. But for those who are not getting the relief they need with established migraine therapies, trying the newer medications, such as CGRPi, could provide a solution. It is also important to keep in mind that triptans are contraindicated for some patients, such as those with a high-risk cardiovascular profile. Additionally, some patients may have contraindications to NSAIDs.
Prevention is another important aspect of migraine care. A September 2024 article in Headache: The Journal of Head and Face Pain used a retrospective cohort analysis of Patient-Reported Outcomes Measurement Information System (PROMIS) data, which included 1245 patients using a variety of migraine preventive therapies: antidepressants, antiseizure medications, beta-blockers, and CGRPi. 4 The researchers reported that patients taking “CGRPi had a statistically significant reduction in pain T-scores (60.4 [standard deviation (SD) 7.4] to 58.4 [SD 8.2], p = 0.003), especially those who switched from other preventative medications to CGRPi.” This, along with the BMJ meta-analysis,3 helps in assessing relative benefits for treatments of acute migraine episodes and for migraine prevention. However, the efficacy of various types of therapy highlights the value of considering all options for each patient.
Individual patient characteristics, particularly contraindications, also play an important role in guiding therapeutic selection. And trial and error remain part of migraine treatment, given that there are no pretesting determinants that can predict treatment success for individual patients. We need to emphasize to patients that effective migraine therapy is obtainable and important — for comfort, quality of life, and possibly overall healthy aging.
References
- Geng D, Liu H, Wang H, Wang H . Telomere length exhibits inverse association with migraine among Americans aged 20-50 years, without implications beyond age 50: a cross-sectional study. Sci Rep. 2024;14:22597. Source
- Fila M, Pawlowska E, Szczepanska J, Blasiak J. Different aspects of aging in migraine. Aging Dis. 2023;14:6. Source
- Karlsson WK, Ostinelli EG, Zhuang ZA, et al. Comparative effects of drug interventions for the acute management of migraine episodes in adults: Systematic review and network meta-analysis. BMJ. 2024;386:e080107. Source
- Peasah SK, Soh YH, Huang Y, Nguyen J, Hanmer J, Good C. Patient reported outcomes and real-world use of calcitonin gene-related peptide medications in migraine. Headache. Published online September 30, 202 Source