A Risk-Difference Meta-Analysis for the Prophylactic Treatments of Chronic Migraine.

Chronic migraine (CM) imposes significant personal, societal, and financial burdens, historically lacking specific prophylactic treatments. Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) represent a novel, mechanism-based, and migraine-specific prophylactic approach. Four mAbs, namely, erenumab, fremanezumab, galcanezumab, and eptinezumab, have been marketed, although head-to-head trials with standard anti-migraine treatments are absent. This study aimed to compare the efficacy and safety of anti-CGRP mAbs with standard anti-migraine treatments using a cross-trial indirect model of the absolute risk difference (ARD) of a 50% responder rate, in order to express the final results in terms of the number needed to treat (NNT) and number needed to harm (NNH). Phase 3 and 2b randomized controlled trials (RCTs) for CM prophylaxis were searched in the MEDLINE and CENTRAL databases with specific inclusion and exclusion criteria. The ARD between groups for the percentage of trial participants who reported a 50% reduction in monthly migraine days and the differences in the number of adverse events (AEs), serious adverse events (SAEs), and participants who withdrew from each RCT were calculated, and subsequently, the NNT and NNH were calculated for each one of the outcome measures. In total, eight RCTs were considered eligible. A similar efficacy and safety have been demonstrated among CGRP mAbs and all standard CM treatments. The results of the ARD for the total number of studies concerning efficacy, total adverse events, serious adverse events, and dropout from the RCTs ranged from -0.688 (95% confidence interval (CI): -0.821-(-0.513)) to -0.018 (95% CI: -0.044-(0.007)), from 0.032 (95% CI: -0.041, 0.104) to -0.380 (95% CI: -0.589, -0.126), from -0.025 (95% CI: -0.046, -0.006) to 0.014 (95% CI: -0.015, 0.42), from 0.048 (95% CI: -0.112, 0.014) to 0.232 (95% CI: -0.016, 0.458) correspondingly. All anti-CGRP mAbs showed a roughly equal statistically significant ARD and similar NNTs, ranging from 5 to 8, while the ARD of onbotulinum toxin A (oBTA) was not significant with an NNT 56. The two studies of topiramate showed contradictory results, the one significant while the other not, with NNTs 2 and 22, respectively. All four anti-CGRP mAbs showed an invariably high efficacy among their studies, in terms of the ARD and its derivative measure of NNT, in contrast to oBTA, while in topiramate, the results are contradictory between the two studies.

Primary headache subtypes and thyroid dysfunction: Is there any association?

BACKGROUND: Primary headaches, and particularly migraine and tension-type headache (TTH) as well as hypothyroidism are common medical conditions. To date, numerous studies have suggested a possible bidirectional relationship between migraine and hypothyroidism, although certain studies had contradictory results. OBJECTIVE: To investigate whether there is any association between primary headache subtypes and thyroid disorders. METHODS: A retrospective study of consecutive patients aged ≥18 years referred to the Headache Outpatient Clinic of Aeginition Hospital and diagnosed with primary headache and any thyroid disorder. RESULTS: Out of 427 patients (males/females=76/351), 253 (59.3%) were diagnosed with migraine without aura, 53 (12.4%) with TTH, 49 (11.5%) with migraine with aura, 29 (6.8%) with medication-overuse headache, 23 (5.4%) with mixed-type headache (migraine with/without aura and TTH), nine (2.1%) with cluster headache, and 11 (2.6%) with other types of primary headaches. The prevalence of any type of thyroid disorder was 20.8% (89/427 patients). In the total sample, 27 patients (6.3%) reported hypothyroidism, 18 (4.2%) unspecified thyroidopathy, 14 (3.3%) thyroid nodules, 12 (2.8%) Hashimoto thyroiditis, 12 (2.8%) thyroidectomy, three (0.7%) thyroid goiter, and three (0.7%) hyperthyroidism. Further statistical analysis between categorical variables did not reveal any significant association between headache subtypes and thyroid dysfunction. CONCLUSIONS: No specific association was found between primary headache subtypes and specific thyroid disorder. However, a high prevalence of thyroid dysfunction in general and specifically hypothyroidism was demonstrated among patients with primary headaches, which lays the foundation for further clarification in prospective longitudinal studies.

Primary headache subtypes and thyroid dysfunction: Is there any association? / Subtipos de cefaleia primária e disfunção tireoidiana: existe alguma associação?

ABSTRACT Background: Primary headaches, and particularly migraine and tension-type headache (TTH) as well as hypothyroidism are common medical conditions. To date, numerous studies have suggested a possible bidirectional relationship between migraine and hypothyroidism, although certain studies had contradictory results. Objective: To investigate whether there is any association between primary headache subtypes and thyroid disorders. Methods: A retrospective study of consecutive patients aged ≥18 years referred to the Headache Outpatient Clinic of Aeginition Hospital and diagnosed with primary headache and any thyroid disorder. Results: Out of 427 patients (males/females=76/351), 253 (59.3%) were diagnosed with migraine without aura, 53 (12.4%) with TTH, 49 (11.5%) with migraine with aura, 29 (6.8%) with medication-overuse headache, 23 (5.4%) with mixed-type headache (migraine with/without aura and TTH), nine (2.1%) with cluster headache, and 11 (2.6%) with other types of primary headaches. The prevalence of any type of thyroid disorder was 20.8% (89/427 patients). In the total sample, 27 patients (6.3%) reported hypothyroidism, 18 (4.2%) unspecified thyroidopathy, 14 (3.3%) thyroid nodules, 12 (2.8%) Hashimoto thyroiditis, 12 (2.8%) thyroidectomy, three (0.7%) thyroid goiter, and three (0.7%) hyperthyroidism. Further statistical analysis between categorical variables did not reveal any significant association between headache subtypes and thyroid dysfunction. Conclusions: No specific association was found between primary headache subtypes and specific thyroid disorder. However, a high prevalence of thyroid dysfunction in general and specifically hypothyroidism was demonstrated among patients with primary headaches, which lays the foundation for further clarification in prospective longitudinal studies.

RESUMO Introdução: Cefaleias primárias e, particularmente, enxaqueca e cefaleia do tipo tensional (CTT), bem como hipotiroidismo, constituem condições médicas comuns. Até o momento, vários estudos sugeriram uma possível relação bidirecional entre enxaqueca e hipotireoidismo, embora alguns estudos tenham resultados contraditórios. Objetivo: Investigar se existe associação entre subtipos de cefaleia primária e distúrbios da tireoide. Métodos: Estudo retrospectivo de pacientes consecutivos com idade ≥18 anos encaminhados ao Ambulatório de Cefaleia do Hospital Aeginition, com diagnóstico de cefaleia primária e qualquer distúrbio da tireoide. Resultados: De 427 pacientes (homens/mulheres=76/351), 253 pacientes (59,3%) foram diagnosticados com enxaqueca sem aura, 53 (12,4%) com CTT, 49 (11,5%) com enxaqueca com aura, 29 (6,8 %) com cefaleia por uso excessivo de medicamentos, 23 (5,4%) com cefaleia mista (enxaqueca com/sem aura e CTT), nove (2,1%) com cefaleia em salvas e 11 (2,6%) com outros tipos de cefaleias primárias. A prevalência de qualquer tipo de distúrbio tireoidiano foi de 20,8% (89/427 pacientes). Na amostra total, 27 pacientes (6,3%) relataram hipotireoidismo, 18 (4,2%) tireoidopatia não especificada, 14 (3,3%) nódulos de tireoide, 12 (2,8%) tireoidite de Hashimoto, 12 (2,8%) tireoidectomia, três (0,7%) bócio da tireoide e três (0,7%) hipertireoidismo. Uma análise estatística posterior entre as variáveis categóricas não revelou qualquer associação significativa entre os subtipos de cefaleia e disfunção tireoidiana. Conclusões: Não encontramos associação entre subtipos de cefaleia primária e distúrbio específico da tireoide. No entanto, foi observada prevalência elevada de disfunção tireoidiana em geral e especificamente hipotireoidismo entre pacientes com cefaleia primária, o que estabelece base para maiores esclarecimentos em estudos longitudinais prospectivos.

Relationship of Migraine and Tension-Type Headache With Hypothyroidism: A Literature Review.

BACKGROUND: Migraine, tension-type headache, and hypothyroidism constitute very common medical conditions. Headache is one of the most common symptoms of hypothyroidism, occurring in approximately one-third of the patients. To date, data about the relationship between migraine and tension-type headache and thyroid dysfunction, and in particular hypothyroidism have been contradictory, while the underlying pathophysiological basis explaining this association is still unclear. OBJECTIVE: In this review, we investigated the association between primary headaches and hypothyroidism, with the aim of shedding light on its pathophysiological basis. METHODS: We conducted a systematic search in the MEDLINE database using both subject headings and keywords for headache, migraine, tension-type headache, thyroid hormones, and hypothyroidism, and we also examined manually the reference lists of all articles that met the inclusion criteria. Included studies were related to headache and thyroid disease comorbidity, with emphasis on hypothyroidism (ideally demonstrated by hormonal measurements), and with the term headache including migraine, tension-type headache, and headache attributed to hypothyroidism (HAH) based on the International Classification of Headache Disorders IIIb. Quality of studies was assessed by the Newcastle-Ottawa scale. RESULTS: Of a total of 640 identified articles, 9 studies were included. Overall, there was vast heterogeneity across the included studies concerning population, study design and outcomes. Two studies investigated the HAH, with emphasis on the clinical characteristics of headache (time of onset, localization, quality, intensity, and response to hormonal replacement treatment). Five studies investigated comorbidity between migraine and thyroid disorders, especially hypothyroidism, and in the majority of them a positive association was demonstrated. One study found that headache, and particularly migraine, may increase the risk of developing hypothyroidism. Finally, only 1 study on chronic tension-type headache found coexistence of migraine and hypoactivity of the hypothalamus-pituitary-thyroid axis. The strengths and limitations of these studies are analyzed and possible pathophysiological mechanisms are suggested. CONCLUSIONS: The existing data are considered inadequate to answer with certainty the relationship between headaches and thyroid disorders. According to our analysis, it seems that suggestions for a possible bidirectional association between headaches and especially migraine and hypothyroidism could exist. It hence lays the foundation for further research into the aforementioned association and its pathogenesis via large prospective multicenter studies.