Headache and Pain Research

Original Article

The Impact of Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies on Sleep Quality and Daytime Sleepiness in Migraine Patients: A Multicenter Study: Rita Cagigal, Ângelo Fonseca, Bárbara Martins, Catarina Fernandes, Sandra Palma, Carolina Guerreiro, Carla Morgado, Diana Valente, Miguel Miranda, Joana Silva, Miguel Saianda-Duarte, Sofia Casanova, Mariana Branco, Ana Luísa Rocha, Henrique Delgado, Elsa Parreira, Filipe Palavra; Headache Pain Res. 2026;27(1):43-51. Published online January 28, 2026; DOI: https://doi.org/10.62087/hpr.2025.0022

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Abstract PDF: Purpose: This study aimed to determine whether patients with migraine experience improvements in self-reported sleep quality and daytime sleepiness after starting monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (CGRP) or its receptor, and to explore the association between treatment efficacy and improvements in sleep quality.
Methods
This prospective, multicenter, observational, longitudinal study was conducted across 12 headache centers. Adults with episodic or chronic migraine who began anti-CGRP mAb therapy were assessed at baseline, 3 months, and 6 months. Sleep quality and daytime sleepiness were evaluated using the Portuguese version of the Pittsburgh Sleep Quality Index (PSQI-PT) and the Portuguese version of the Epworth Sleepiness Scale (ESS-PT), respectively.
Results
Of 118 enrolled patients, 109 completed the study (86.4% female; mean age, 43.6 years). A significant improvement in sleep quality was observed, with median PSQI-PT scores decreasing from 9 at baseline to 6 at 6 months (p<0.001). Daytime sleepiness also improved, with median ESS-PT scores decreasing from 7 to 6 (p=0.04). Migraine frequency decreased significantly, from a median of 13 to 4 monthly migraine days (p<0.001). Greater migraine improvement was independently associated with greater PSQI-PT improvement (p<0.001), whereas changes in ESS-PT were not correlated with treatment efficacy.
Conclusion
Anti-CGRP mAb therapy was associated with significant improvements in sleep quality, likely mediated through migraine relief. Changes in ESS-PT were not correlated with treatment efficacy, suggesting a possible interaction between migraine mechanisms and CGRP-mediated sleep–wake regulation. Future research should focus on clarifying the mechanisms underlying these associations.

Review Article

Morning Headaches: An In-depth Review of Causes, Associated Disorders, and Management Strategies: Yooha Hong, Mi-Kyoung Kang, Min Seung Kim, Heejung Mo, Rebecca C. Cox, Hee-Jin Im; Headache Pain Res. 2025;26(1):66-79. Published online January 17, 2025; DOI: https://doi.org/10.62087/hpr.2024.0023

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Abstract PDF: Morning headaches, which are defined by occurrence upon or shortly after waking up in the morning, range from mild discomfort to severe pain and significantly impact an individual’s quality of life. Although morning headaches are a prevalent and potentially debilitating condition, the criteria for defining these headaches vary. The lack of universally accepted diagnostic criteria complicates understanding their etiology, associated factors, and potential interventions. The causes of morning headaches are multifaceted, including primary headache disorders like migraines and cluster headaches, and secondary causes such as sleep disorders, hypertension, abnormal intracranial pressure, and brain parenchymal diseases. Psychological factors, including anxiety and depression, as well as substance use, further complicate the clinical presentation, often requiring a multidisciplinary approach for effective diagnosis and treatment. This review provides a comprehensive overview of morning headaches, examining their various aspects and possible treatment options, with the goal of enhancing clinicians’ understanding and management of this common yet often overlooked condition.

Original Article

Cluster Headache Characteristics and the Severity of Obstructive Sleep Apnea: Insights from Polysomnography Analysis: Yooha Hong, Mi-Kyoung Kang, Min Kyung Chu, Soo-Jin Cho, Hee-Jin Im; Headache Pain Res. 2024;25(1):63-71. Published online April 16, 2024; DOI: https://doi.org/10.62087/hpr.2024.0001

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Abstract PDF

Purpose: Cluster headache (CH) is characterized by circadian rhythmicity of the attacks, and it is known to respond exceptionally well to oxygen therapy. Furthermore, obstructive sleep apnea (OSA) frequently co-occurs with CH, and both conditions may be parallel outcomes of hypothalamic dysfunction rather than being causally related. The aim of this study was to analyze the association between CH characteristics and polysomnographic factors stratified by the severity of OSA in patients diagnosed with CH and OSA.
Methods
We retrospectively analyzed the data of OSA patients with CH who were enrolled in the Korean Cluster Headache Registry and underwent polysomnography due to clinical suspicion of OSA. Basic demographic data, headache-related parameters, and polysomnographic parameters were analyzed according to the severity of OSA (apnea-hypopnea index: <15 or ≥15 per hour).
Results
Twelve CH patients with OSA were evaluated. The onset age of CH was higher (38.5 years vs. 19.0 years, p=0.010), and the maximal duration of cluster bouts was longer (156.5 days vs. 47.0 days, p=0.037) in the moderate-to-severe OSA group than in the mild OSA group. Unlike other polysomnographic parameters, the apnea-hypopnea index and respiratory arousal index during rapid eye movement (REM) sleep were comparable across different OSA severity levels.
Conclusion
The onset age and duration of cluster bouts were associated with the severity of OSA in CH patients. Additionally, the relatively high susceptibility to hypoxia during REM sleep in patients with mild OSA implies that interventions may be potentially advantageous, even in CH patients with mild OSA.

Citations

Citations to this article as recorded by

Morning Headaches: An In-depth Review of Causes, Associated Disorders, and Management Strategies
Yooha Hong, Mi-Kyoung Kang, Min Seung Kim, Heejung Mo, Rebecca C. Cox, Hee-Jin Im
Headache and Pain Research.2025; 26(1): 66. CrossRef
Inverse association of obesity with bout periodicity in episodic cluster headache: a multicenter cross-sectional study
Byung-Su Kim, Mi Ji Lee, Byung-Kun Kim, Jong-Hee Sohn, Tae-Jin Song, Min Kyung Chu, Soo-Kyoung Kim, Jeong Wook Park, Heui-Soo Moon, Pil-Wook Chung, Soo-Jin Cho
The Journal of Headache and Pain.2025;[Epub] CrossRef
Subtype shift, relapse rate and risk factors of frequent relapse in cluster headache: A multicenter, prospective, longitudinal observation
Mi Ji Lee, Soo-Kyoung Kim, Min Kyung Chu, Jae Myun Chung, Heui-Soo Moon, Pil-Wook Chung, Jeong Wook Park, Byung-Kun Kim, Kyungmi Oh, Yun-Ju Choi, Jong-Hee Sohn, Byung-Su Kim, Dae Woong Bae, Daeyoung Kim, Tae-Jin Song, Kwang-Yeol Park, Soo-Jin Cho
Cephalalgia.2025;[Epub] CrossRef

Reiview Article

Sleep Disorders in Headache Patients: Hye Jeong Lee, Hee-Jin Im, Soo-Jin Cho, Min Kyung Chu; Korean J Headache. 2023;24(1):1-10. Published online June 30, 2023

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Abstract PDF: Headache disorders and sleep problems are common conditions with a high prevalence in the general population, and impose a considerable socio-economic burden. They show a close association with headache disorders through various relationship. The prevalence of sleep problems is elevated in individuals with headache, especially for migraine. In most headache disorders, sleep problems are accompanied by the deterioration of clinical characteristics of headache disorders. The sharing brain structures and neurotransmitters involved in the pathogenesis of headache disorders and sleep disorders may be an explanation for the close relationship between two disorders. In this article, we briefly review the relationship of headache disorders with sleep disorders including insomnia, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, parasomnias, and sleep related movement disorders.

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