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Background
The aim of this work is to analyze the reports on cluster headache attacks collected online in the citizen science project CLUE with respect to the effectiveness of drugs taken during the attacks. The collection of data within the framework of citizen science projects opens up the possibility of investigating the effectiveness of acute m...
Citations
... Interestingly, treatment efficacy differs greatly between episodic and chronic CH patients. Patients with chronic CH were less likely to respond to intranasal zolmitriptan [102] or oxygen therapy [103]. Verapamil is almost 50% less likely to be effective in patients with chronic CH compared to those with episodic CH [104]. ...
Cluster headache and migraine are regarded as distinct primary headaches. While cluster headache and migraine differ in multiple aspects such as gender-related and headache specific features (e.g., attack duration and frequency), both show clinical similarities in trigger factors (e.g., alcohol) and treatment response (e.g., triptans). Here, we review the similarities and differences in anatomy and pathophysiology that underlie cluster headache and migraine, discuss whether cluster headache and migraine should indeed be considered as two distinct primary headaches, and propose recommendations for future studies.
Graphical Abstract
Video recording of the debate held at the 1st International Conference on Advances in Migraine Sciences (ICAMS 2022, Copenhagen, Denmark) is available at https://www.youtube.com/watch?v=uUimmnDVTTE .
... The results of all previous studies were obtained using self-reported questionnaires, and the studies did not directly determine attack frequencies during school and vacation periods. The CLUE research project directly determined migraine attacks, thereby creating a database for future studies [8,9]. ...
This citizen science project CLUE compared the attack frequency between school and vacation periods among adolescents. The data collection process adopted in citizen science projects opens up the possibility of conducting analyses by including a large number of participants over a long period and across different regions. The data on 684 migraine attacks reported by 68 adolescents aged 16 to 19 years were collected using an online platform and smartphone apps. A Fisher’s exact test was used to compare the distributions of the migraine attack frequency during vacation and school periods in two different scenarios. In both scenarios, the attack frequency during school periods was significantly higher than that during vacation periods. The use of web-based data collection has some methodological limitations; however, it enabled the measurement of relative migraine attack frequency in students during vacation and school periods. The higher prevalence of migraine during school periods indicates the requirement of increasing headache awareness among children.
... 22 Additional evidence suggesting subtle pathophysiological differences between patients with ECH and CCH include differences in response to the same treatment, as seen in examples from clinical trials to date with lithium 26,27 (efficacious in CCH but not ECH) and galcanezumab 28,29 (efficacious in ECH but not CCH) in preventive treatment, as well as non-invasive vagus nerve stimulation for acute treatment (efficacious in ECH but not CCH). 30,31 However, some CH treatments, particularly acute treatments such as subcutaneous and intranasal triptans and oxygen are efficacious in both ECH and CCH, [32][33][34][35][36] although some studies have reported differences in the magnitude of response. 32,33,35 Treatments to interrupt cluster periods or reduce the frequency of attacks (i.e., preventive treatment) are generally based on recommendations from treatment guidelines. ...
... 30,31 However, some CH treatments, particularly acute treatments such as subcutaneous and intranasal triptans and oxygen are efficacious in both ECH and CCH, [32][33][34][35][36] although some studies have reported differences in the magnitude of response. 32,33,35 Treatments to interrupt cluster periods or reduce the frequency of attacks (i.e., preventive treatment) are generally based on recommendations from treatment guidelines. 37,38 However, these guidelines are based on a small number of randomized controlled trials (RCTs) supplemented with data from uncontrolled trials. ...
Objective:
To provide a review of challenges in clinical trials for the preventive treatment of cluster headache (CH) and highlight considerations for future studies.
Background:
Current guidelines for preventive treatment of CH are largely based on off-label therapies supported by a limited number of small randomized controlled trials. Guidelines for clinical trial design for CH treatments from the International Headache Society were last issued in 1995.
Methods/results:
Randomized controlled clinical trials were identified in the European and/or United States clinical trial registries with a search term of "cluster headache," and manually reviewed. Cumulatively, there were 27 unique placebo-controlled prevention trials for episodic and/or chronic CH, of which 12 were either ongoing, not yet recruiting, or the status was unknown. Of the remaining 15 trials, 5 were terminated early and 7 of the 10 completed trials enrolled fewer patients than planned or did not report the planned sample size. A systematic search of PubMed was also utilized to identify published manuscripts reporting results from placebo-controlled preventive trials of CH. This search yielded 16 publications, of which 7 were registered. Through critical review of trial data and published manuscripts, challenges and complexities encountered in clinical trials for the preventive treatment of CH were identified. For example, the excruciating pain associated with CH demands a suitably limited baseline duration, rapid treatment efficacy onset, and poses a specific issue regarding duration of investigational treatment period and length of exposure to placebo. In episodic CH, spontaneous remission as part of natural history, and the unpredictability and irregularity of cluster periods across patients present additional key challenges.
Conclusions:
Optimal CH trial design should balance sound methodology to demonstrate efficacy of a potential treatment with patient needs and the natural history of the disease, including unique outcome measures and endpoint timings for chronic versus episodic CH.
... As previous literature provided evidence related to the efficacy of oxygen treatment in CH patients [56], oxygen should be considered as an additional treatment for CH care. However, because of the controversies surrounding the inclusion of oxygen as a drug [57][58][59], we could not include studies with oxygen, and we expect more future studies evaluating oxygen as CH treatment. ...
It is important to find effective and safe pharmacological options for managing cluster headache (CH) because there is limited evidence from studies supporting the general efficacy and safety of pharmacological therapies. This systematic review and network meta-analysis (NMA) analyzed published randomized controlled trials (RCTs) to evaluate the efficacy and safety of pharmacological treatments in patients with CH. The PubMed and Embase databases were searched to identify RCTs that evaluated the efficacy and safety of pharmacological treatments for CH. Efficacy outcomes included frequency and duration of attacks, pain-free rate, and the use of rescue agents. Safety outcomes were evaluated based on the number of patients who experienced adverse events. A total of 23 studies were included in the analysis. The frequency of attacks was reduced (mean difference (MD) = −1.05, 95% confidence interval (CI) = −1.62 to −0.47; p = 0.0004), and the pain-free rate was increased (odds ratio (OR) = 3.89, 95% CI = 2.76–5.48; p < 0.00001) in the pharmacological treatment group, with a lower frequency of rescue agent use than the placebo group. Preventive, acute, and triptan or non-triptan therapies did not show significant differences in efficacy (p > 0.05). In the NMA, different results were shown among the interventions; for example, zolmitriptan 5 mg was more effective than zolmitriptan 10 mg in the pain-free outcome (OR = 0.40, 95% CI = 0.19–0.82; p < 0.05). Pharmacological treatment was shown to be more effective than placebo to manage CH with differences among types of therapies and individual interventions, and it was consistently shown to be associated with the development of adverse events. Thus, individualized therapy approaches should be applied to treat CH in real-world practice.
