Efficacy and safety of oral zolmitriptan in the preictal phase of episodic cluster headache

BackgroundRecent studies on cluster headache suggested that headache includes three phases.Oral zolmitriptan is effective in the treatment of acute headache attack.We aim to describe the clinical characteristics of different phases of episodic cluster headache(eCH) and observe the efficacy and safety of oral zolmitriptan in preictal phase of eCH attacks.MethodsForty-eight patients with eCH were enrolled in this study. We divided the CH attack into three phases: preictal, ictal and postictal phase and analyzed the clinical features of each phase. We collected the data of twenty-three patients who took zolmitriptan in the preictal phase of three consecutive CH attacks. The Visual Analogue Scale (VAS) score and duration of headache after three consecutive treatments were compared with the baseline respectively. Chi square test, t test, Mann Whitney U test, Pearson linear correlation analysis, paired t-test and paired non-parametric rank-sum test were used for statistical analysis.ResultsForty-five patients (93.8%) reported the presence of preictal symptoms. The most frequent preictal symptom was mild to moderate head discomfort in the area of the subsequent serious headache, accounting for 87.5%. The duration of preictal period was positively correlated with the duration of headache. The Pearson correlation coefficient was 0.313 (P=0.018). Among the twenty-three patients taking oral zolmitriptan in the preictal phase, the VAS max score was significantly lower than that of baseline headache (P<0.01). The duration of headache after three preictal administration was significantly shorter than that of baseline headache (P<0.01). The incidence of adverse reactions after taking zolmitriptan was 10.1%, including head drowsiness, neck stiffness and mild chest tightness.Conclusions Preictal symptoms were common in CH. Mild to moderate discomfort in the subsequent serious headache was the most common symptom in the preictal phase. Oral administration of zolmitriptan in the preictal period could reduce the severity of headache and shorten the duration of headache in a cluster period without serious adverse reactions.

Effectiveness of medication in cluster headache

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 medication on the basis of a large number of individual attacks instead of a simple survey of patients. Methods Data from 8369 cluster headache attacks, containing information about acute medication taken and the assessment of its effect, were collected from 133 participants using an online platform and a smartphone app. Chi-square tests were used to investigate whether the effect of the three recommended acute drugs differs when distinguishing between participants with chronic or episodic cluster headache. Furthermore, it was investigated whether there are differences between smokers and non-smokers in the assessment of the effect of the acute medication. Results Our participants rated the effectiveness of sumatriptan 6 mg s.c. as significantly better than oxygen and zolmitriptan nasal spray. Oxygen is considered to be significantly better in episodic versus chronic cluster headache, and sumatriptan is considered to be significantly better in chronic versus episodic cluster headache. Smokers rate the effect of oxygen as significantly better than non-smokers. Conclusions Despite some methodological limitations, web-based data collection is able to support findings from clinical trials in a real world setting about effectiveness of acute cluster headache treatment in several situations.

Comprehensive clinical phenotyping of nitroglycerin infusion induced cluster headache attacks

Background Nitroglycerin administration allows the study of cluster headache attacks in their entirety in a standardised way. Methods A single-blind, placebo-controlled, cross-over study using weight-calculated intravenous nitroglycerin administration at 0.5 µg/kg/min over 20 minutes to study cluster headache attacks, including accompanying non-headache symptoms and cranial autonomic symptoms. Results Thirty-three subjects with cluster headache were included in the study; 24 completed all three study visits. Nitroglycerin-induced attacks developed in 26 out of 33 subjects (79%) receiving unblinded nitroglycerin infusion, and in 19 out of 25 subjects (76%) receiving single-blinded nitroglycerin infusion, compared with one out of 24 subjects (4%) receiving single-blinded placebo infusion. Episodic cluster headache subjects had a shorter latency period to a nitroglycerin-induced attack compared to the chronic cluster headache (CCH) subjects ( U = 15, z = −2.399, p = 0.016). Sixteen of nineteen episodic cluster headache (mean, 84%; 95% confidence interval, 66–100%) and 11 of 14 chronic cluster headache subjects developed a nitroglycerin-induced attack (79%, 54–100%) following the unblinded nitroglycerin infusion. Following the single-blinded nitroglycerin infusion, eight out of 13 episodic cluster headache (62%, 31–92%) and 11 out of 12 chronic cluster headache (92%, 73–100%) subjects developed nitroglycerin-induced attacks. Nitroglycerin induced non-headache symptoms in the majority of subjects receiving it: 91% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visits, compared with 33% in the single-blinded placebo visit. Cranial autonomic symptoms were induced by nitroglycerin infusion, 94% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visit, compared with 17% in the single-blinded placebo visit. Conclusion Intravenous weight-adjusted nitroglycerin administration in both episodic cluster headache in bout and chronic cluster headache is effective and reliable in inducing cluster headache attacks, cranial autonomic symptoms and non-headache symptoms.

Prevalence of pre-cluster symptoms in episodic cluster headache: Is it possible to predict an upcoming bout?

Background Early symptoms prior to a cluster headache bout have been reported to occur days or weeks before the actual beginning of the cluster headache bouts. This study aimed to describe the prevalence of pre-cluster (premonitory) symptoms and examine the predictability of an upcoming cluster headache bout. Methods 100 patients with episodic cluster headache were included in this retrospective cross-sectional study. All patients underwent a semi-structured interview including 25 questions concerning pre-cluster symptoms. Results Pre-cluster symptoms were reported by 86% of patients with a mean of 6.8 days (interquartile range 3–14) preceding the bout. An ability to predict an upcoming bout was reported by 57% with a mean 4.6 days (interquartile range 2–7) before the bout. Occurrence of shadow attacks was associated with increased predictability (odds ratio: 3.06, confidence interval: 1.19–7.88, p-value = 0.020). In remission periods, 58% of patients reported mild cluster headache symptoms and 53% reported occurrence of single shadow attacks. Conclusions The majority of episodic cluster headache patients experienced pre-cluster symptoms, and more than half could predict an upcoming bout, suggesting the significant potential of early intervention. Furthermore, the experience of mild cluster headache symptoms and infrequent shadow attacks in remission periods is common and suggest an underlying pathophysiology extending beyond the cluster headache bouts.

Efficacy of galcanezumab in patients with episodic cluster headaches and a history of preventive treatment failure

Objective: The efficacy of galcanezumab was evaluated in patients with episodic cluster headache and history of preventive treatment failure. Methods: In the randomized, 8-week, double-blind study (CGAL), patients with episodic cluster headache received once-monthly subcutaneous injections of galcanezumab 300 mg or placebo. Patients who completed CGAL and enrolled in an open-label study were queried for preventive treatment history. In a subset of patients with a known history of failure of verapamil or any other prior preventive treatment, a post hoc analysis of least square mean change from baseline in weekly cluster headache attack frequency across Weeks 1 to 3 was assessed. Results: Fifteen patients provided data for known history of prior preventive treatment failure (6 placebo, 9 galcanezumab), of whom 11 failed verapamil. The mean reduction in the weekly frequency of cluster headache attacks was greater with galcanezumab compared to placebo among patients with prior preventive treatment failure (8.2 versus 2.4); mean difference 5.8 (95% confidence interval [CI] 2.0, 13.6) and among patients with verapamil failure (10.1 versus 1.6); mean difference 8.5 (95% CI 0.4, 16.7). Conclusion: In this exploratory analysis of patients with a known history of prior preventive treatment failures, treatment with galcanezumab resulted in greater mean reductions in weekly cluster headache attacks compared with placebo. ClinicalTrials.gov: NCT02397473 (I5Q-MC-CGAL) NCT02797951 (I5Q-MC-CGAR)