Acute Treatment Of Cluster Headache Research Articles

The Role of CGRP Monoclonal Antibodies in the Treatment of Acute Cluster Headache

This article discusses the role of Calcitonin Gene-Related Peptide antagonists available on the market in treating cluster headaches. All the treatments discussed in this article focus on either abortive, preventive, or transitional care. These therapies include Monoclonal Antibodies (Galcanezumab, Fremanezumab, Erenumab), high-flow oxygen, triptans (sumatriptan, zolmitriptan), Octreotide, non-invasive vagus nerve stimulation (vagus and sphenopalatine nerves), and other medications like dihydroergotamine, lidocaine, and capsaicin. We reviewed many studies from The United States since 2015; analytical methods were utilized. Moreover, we found that some of the treatment options for CH can vary depending on efficacy and route of administration and according to categories of therapy (acute or preventive). Every treatment has a specific and unique mechanism of action, indications, contraindications, and side effects. Therefore, the recommendation of one particular treatment should be considered in the success of the treatment of Cluster Headaches. Monoclonal Antibodies against CGRP have a unique role and are considered a first alternative in treating acute CH.

Clínica y fisiopatología de la cefalea en racimos. Acercamiento a la indicación de neuroestimulación combinada occipital y supraorbitaria

Cluster headache (CH) is included under section 3 - Trigeminal autonomic cephalalgias (TAC) of the International Headache Society (IHS) classification. It is one of the most frequent, painful and disabling primary headaches. Acute and preventive pharmacological treatments are often poorly tolerated and of limited effectiveness. Due to improved understanding of the pathophysiology of CH, neuromodulation devices are now considered safe and effective options for preventive and acute treatment of CH. In this paper, we review the information available to date, and present the case of a patient with disabling cluster headache highly resistant to medical treatment who underwent implantation of a peripheral nerve neurostimulation system to stimulate the supraorbital nerves (SON) and greater occipital nerve (GON) in our Pain Unit. We also review the diagnostic criteria for CH, the state of the knowledge on the pathophysiology of CH, and the role played by neuromodulation in treating this condition

Patient experience with non-invasive vagus nerve stimulator: gammaCore patient registry.

gammaCore is cleared by the FDA for acute and preventive treatment of cluster headache and the acute treatment of migraine in adults. Previously, only 2 treatments were approved for acute treatment of cluster headache while none were approved for preventive treatment. Following the initial FDA clearance, based on the ACT-1 and ACT-2 studies, a gammaCore Patient Registry (GPR) was designed to provide insights on the use of gammaCore and prescription patterns in the real-world setting and to characterize respective benefits and challenges during the acute treatment of episodic cluster headache. GPR was a prospective observational registry in which patients with episodic cluster headache (3rd edition of the International Classification of Headache Disorders criteria) who were prescribed gammaCore were invited to voluntarily enroll and provide information on their experiences between July 2017 and June 2018. Participants provided baseline information and were trained to self-administer treatment with gammaCore for cluster pain. Participants were also requested to record information for each cluster attack. Of the 182 patients who provided baseline demographic and cluster headache characteristics, 152 provided health index baseline data using EuroQol Health Index tool, 5-level format (EQ5D-5L) and 17 patients provided attack data on a total of 192 cluster headache attacks. The mean age was 49 years; 65% were male and 82% were white; the mean number of months of known diagnosis of cluster headache was 57; the mean number of attacks per cluster headache 4-week period was 14; and the mean pain score was 3.7 (0-4 scale) with a mean attack duration of 74 minutes. Sixty-seven percent of patients had used preventive treatments and 83% had used abortive treatments for cluster headaches; 25% of participants reported at least 1 comorbidity. The mean EQ5D-5L score (scale 0-1) was 0.83. Of the 192 cluster headache attacks reported, gammaCore was used in 116 (60%) attacks. Within this group, the mean pain score at the start of the attacks was 2.7, the mean number of stimulations used was 3.6, and the pain score after 30 minutes was 1.3. At 30 minutes, the pain of 81 (70%) attacks was reduced to none (27%) or mild (43%) (a pain score of 0 or 1) and in 94 (81%) attacks, patients experienced a reduction of at least 1 point in the pain score. This real-world observational evidence suggests that gammaCore adds clinically meaningful value to patients with episodic cluster headache by providing rapid pain relief and confirms that there is significant interest among prescribers in providing this new treatment and technology. This evidence further supports the need to redefine gammaCore as no longer investigational or experimental during considerations for reimbursement.

Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A meta-analysis.

BackgroundTwo randomized, double-blind, sham-controlled trials (ACT1, ACT2) evaluated non-invasive vagus nerve stimulation (nVNS) as acute treatment for cluster headache. We analyzed pooled ACT1/ACT2 data to increase statistical power and gain insight into the differential efficacy of nVNS in episodic and chronic cluster headache.MethodsData extracted from ACT1 and ACT2 were pooled using a fixed-effects model. Main outcome measures were the primary endpoints of each study. This was the proportion of participants whose first treated attack improved from moderate (2), severe (3), or very severe (4) pain intensity to mild (1) or nil (0) for ACT1 and the proportion of treated attacks whose pain intensity improved from 2–4 to 0 for ACT2.ResultsThe pooled population included 225 participants (episodic: n = 112; chronic: n = 113) from ACT1 (n = 133) and ACT2 (n = 92) in the nVNS (n = 108) and sham (n = 117) groups. Interaction was shown between treatment group and cluster headache subtype (p < 0.05). nVNS was superior to sham in episodic but not chronic cluster headache (both endpoints p < 0.01). Only four patients discontinued the studies due to adverse events.ConclusionsnVNS is a well-tolerated and effective acute treatment for episodic cluster headache.Trial registrationThe studies were registered at clinicaltrials.gov (ACT1: NCT01792817; ACT2: NCT01958125).

Psychoactive substances as a last resort\u2014a qualitative study of self-treatment of migraine and cluster headaches

BackgroundTreatment resistant cluster headache and migraine patients are exploring alternative treatments online. The aim of this study was to improve comprehension regarding the use of non-established or alternative pharmacological treatments used by sufferers of cluster headaches and migraines.MethodsA qualitative thematic analysis of the users’ own accounts presented in online forum discussions were conducted. The forum boards https://shroomery.org/, http://bluelight.org, and https://clusterbusters.org/ met the inclusion criteria and were used for the study.ResultsThe analysis resulted in six themes: a desperate need for effective treatments; the role of the forum—finding alternative treatments and community support; alternative treatment substances; dosage and regimens; effects and treatment results; and adverse effects. The results provide an insight into why, how, and by which substances and methods sufferers seek relief from cluster headache and migraines.ConclusionsThese patients are in a desperate and vulnerable situation, and illicit psychoactive substances are often considered a last resort. There appeared to be little or no interest in psychoactive effects per se as these were rather tolerated or avoided by using sub-psychoactive doses. Primarily, psilocybin, lysergic acid diethylamide, and related psychedelic tryptamines were reportedly effective for both prophylactic and acute treatment of cluster headache and migraines. Treatment results with cannabis were more unpredictable. No severe adverse events were reported, but it was observed how desperation sometimes spurred risky behavior when obtaining and testing various treatment alternatives. The forum discourse mainly revolved around maximizing treatment results and minimizing potential harms.

Prescribing Oxygen for Cluster Headache: A Guide for the Provider.

Oxygen is the standard of care for acute treatment of cluster headache. CMS, the US Centers for Medicaid and Medicare Services, has made the indefensible decision to not cover oxygen for cluster headache for patients with Medicaid and Medicare insurance, despite the evidence and professional guidelines. Commercial insurance generally covers oxygen for cluster headache. This is a "how-to" guide for successfully prescribing oxygen in the US. Prescription information is provided that can be incorporated as dot phrases, smart sets, or other standard templates for prescribing oxygen for cluster patients. In many states, oxygen is affordable and can be prescribed for Medicaid and Medicare patients who wish to pay cash. Welding or nonmedical grade industrial oxygen is almost the same cost as medical oxygen. However, it is less pure, lacks the same inspection of tanks, and is delivered without regulators to provide appropriate flow rates. Patients who pay cash should be strongly encouraged to buy medical oxygen.

Vagus Nerve Stimulation for the Acute Treatment of Cluster Headache

Vagus Nerve Stimulation for the Acute Treatment of Cluster Headache

Non-Invasive Vagus Nerve Stimulation for the ACute Treatment of Cluster Headache: Findings From the Randomized, Double-Blind, Sham-Controlled ACT1 Study.

ObjectiveTo evaluate non‐invasive vagus nerve stimulation (nVNS) as an acute cluster headache (CH) treatment.BackgroundMany patients with CH experience excruciating attacks at a frequency that is not sufficiently addressed by current symptomatic treatments.MethodsOne hundred fifty subjects were enrolled and randomized (1:1) to receive nVNS or sham treatment for ≤1 month during a double‐blind phase; completers could enter a 3‐month nVNS open‐label phase. The primary end point was response rate, defined as the proportion of subjects who achieved pain relief (pain intensity of 0 or 1) at 15 minutes after treatment initiation for the first CH attack without rescue medication use through 60 minutes. Secondary end points included the sustained response rate (15‐60 minutes). Subanalyses of episodic cluster headache (eCH) and chronic cluster headache (cCH) cohorts were prespecified.ResultsThe intent‐to‐treat population comprised 133 subjects: 60 nVNS‐treated (eCH, n = 38; cCH, n = 22) and 73 sham‐treated (eCH, n = 47; cCH, n = 26). A response was achieved in 26.7% of nVNS‐treated subjects and 15.1% of sham‐treated subjects (P = .1). Response rates were significantly higher with nVNS than with sham for the eCH cohort (nVNS, 34.2%; sham, 10.6%; P = .008) but not the cCH cohort (nVNS, 13.6%; sham, 23.1%; P = .48). Sustained response rates were significantly higher with nVNS for the eCH cohort (P = .008) and total population (P = .04). Adverse device effects (ADEs) were reported by 35/150 (nVNS, 11; sham, 24) subjects in the double‐blind phase and 18/128 subjects in the open‐label phase. No serious ADEs occurred.ConclusionsIn one of the largest randomized sham‐controlled studies for acute CH treatment, the response rate was not significantly different (vs sham) for the total population; nVNS provided significant, clinically meaningful, rapid, and sustained benefits for eCH but not for cCH, which affected results in the total population. This safe and well‐tolerated treatment represents a novel and promising option for eCH. ClinicalTrials.gov identifier: NCT01792817.

Oxygen therapy for cluster headache. A mask comparison trial. A single-blinded, placebo-controlled, crossover study.

Purpose The purpose of this article is to investigate possible differences in effect between three types of masks in the acute treatment of cluster headache (CH). Patients and methods Fifty-seven CH patients according to ICHD-II-criteria participated in a single-blinded, semi-randomized, placebo-controlled, crossover inpatient study, and 102 CH attacks were treated with 100% oxygen delivered by demand valve oxygen (DVO), O2ptimask or simple mask (15 liters/min) or placebo delivered by DVO for 15 minutes. Primary endpoint: Two-point decrease of pain on a five-point rating scale within 15 minutes. Results Only 10 CH patients had multiple attacks and reached the point of placebo. There were no significant differences between masks in the primary endpoints ( p = 0.412). After 15 minutes 48% had a two-point decrease using the DVO compared to 45% with placebo ( p = 0.867). After 30 minutes 68% were pain free or had pain relief using DVO and 45% by placebo ( p = 0.061). The DVO was preferred by 62% compared to 5% and 33% for simple mask ( p < 0.0001) and O2ptimask ( p = 0.061). In the first attack the DVO was significantly better at achieving pain relief at 15 minutes ( p = 0.018). Treatment with DVO or O2ptimask reduced the need for rescue medication compared to the simple mask (23%, 19%, 50%, respectively). No treatment-related adverse events were observed. Conclusion The primary endpoint with pain relief at 15 minutes was non-significant; however, a post hoc analysis of the first attack significantly favored DVO. Further, therapy by O2ptimask and DVO resulted in a decreased need for rescue medication. We recommend that CH patients be offered DVO or O2ptimask before oxygen therapy is abandoned.

Cluster headache.

Cluster headache.

Triptans for acute cluster headache.

This is an updated version of the original Cochrane review published in Issue 4, 2010 (Law 2010). Cluster headache is an uncommon,severely painful, and disabling condition, with rapid onset. Validated treatment options are limited; first-line therapy includes inhaled oxygen. Other therapies such as intranasal lignocaine and ergotamine are not as commonly used and are less well studied. Triptans are successfully used to treat migraine attacks and they may also be useful for cluster headache. To assess the efficacy and tolerability of the triptan class of drugs compared to placebo and other active interventions in the acute treatment of episodic and chronic cluster headache in adult patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, EMBASE, ClinicalTrials.gov, and reference lists for studies from inception to 22 January 2010 for the original review, and from 2009 to 4 April 2013 for this update. Randomised, double-blind, placebo-controlled studies of triptans for acute treatment of cluster headache episodes. Two review authors independently assessed study quality and extracted data. Numbers of participants with different levels of pain relief,requiring rescue medication, and experiencing adverse events and headache-associated symptoms in treatment and control groups were used to calculate relative risk and numbers needed to treat for benefit (NNT) and harm (NNH). New searches in 2013 did not identify any relevant new studies.All six included studies used a single dose of triptan to treat an attack of moderate to severe pain intensity. Subcutaneous sumatriptan was given to 131 participants at a 6 mg dose, and 88 at a 12 mg dose. Oral or intranasal zolmitriptan was given to 231 participants ata 5 mg dose, and 223 at a 10 mg dose. Placebo was given to 326 participants.Triptans were more effective than placebo for headache relief and pain-free responses. By 15 minutes after treatment with subcutaneous sumatriptan 6 mg, 48% of participants were pain-free and 75% had no pain or mild pain (17% and 32% respectively with placebo).NNTs for subcutaneous sumatriptan 6 mg were 3.3 (95% CI 2.4 to 5.0) and 2.4 (1.9 to 3.2) respectively. Intranasal zolmitriptan 10mg was of less benefit, with 12% of participants pain-free and 28% with no or mild pain (3% and 7% respectively with placebo).NNTs for intranasal zolmitriptan 10 mg were 11 (6.4 to 49) and 4.9 (3.3 to 9.2) respectively. Based on limited data, subcutaneous sumatriptan 6 mg was superior to intranasal zolmitriptan 5 mg or 10 mg for rapid (15 minute)responses, which are important in this condition. Oral routes of administration are not appropriate.

Cluster headache and oxygen: is it possible to predict which patients will be relieved? A prospective cross-sectional correlation study

Response to 100 % oxygen as acute treatment for cluster headache is relative low considering certain subgroups or predictors. The primary purpose of the present study was to find prospectively which factors differ between responders and non-responders to oxygen therapy. The second goal was to find whether any of these differences would clarify the mechanism of pain reduction by oxygen and cluster headache pathophysiology. Patients diagnosed with cluster headache according to the ICHD-II criteria, who started on oxygen therapy (n = 193), were recruited from 51 outpatient clinics and via patient websites in The Netherlands. Patients had to return two questionnaires around the start of oxygen therapy (n = 120). Eventually, 94 patients were included. Clear non- plus moderate responders had ever used pizotifen more often (p = 0.03). Clear non-responders more often had photophobia or phonophobia during cluster headache attacks (p = 0.047) and more often had used triptans in the same active phase as the phase in which they had used oxygen for the first time (p = 0.02). Using correction for multiple testing, we could only confirm a statistically significant difference in triptan use. We were unable to locate the level of action of oxygen in the thalamus and cortex or confirm the sites of its action presently known, solely based on current knowledge of photophobia circuits. However, we conclude that particularly the higher frequency of photophobia or phonophobia in clear non-responders deserves further study to understand the mechanism of pain reduction by oxygen and cluster headache pathophysiology.

Demand Valve Oxygen: A Promising New Oxygen Delivery System for the Acute Treatment of Cluster Headache

To show that demand valve oxygen is an effective acute treatment for cluster headache and to compare this oxygen delivery technique with standard cluster headache therapy of continuous flow oxygen. Single-center, open-label, two-period, two-treatment crossover design, pilot study was used. Subjects treated with one of two sequences: first, headache treated with continuous flow oxygen (100% oxygen at 15 liters per minute), and subsequent with demand valve oxygen, or vice versa. Treatment began when pain was at least moderate. Subjects taught a specific breathing technique for demand valve oxygen that included initial period of hyperventilation. Primary end point was headache response (moderate-to-very-severe pain reduced to mild or none) after 30 minutes of treatment. Three subjects completed the trial, while a fourth completed demand valve oxygen only. All had chronic cluster headache. All subjects treated with demand valve oxygen became pain-free (time in minutes: 15, 19, 6, 8). Three of four had no recurrence within 24 hours. Demand valve oxygen reduced cranial autonomic symptoms in all and resolved them in two subjects. For continuous flow oxygen, two of three subjects became pain-free (20, 10 minutes). Continuous flow oxygen reduced but did not eliminate cranial autonomic symptoms. Continuous flow oxygen had higher recurrence rates. No adverse events noted with either treatment. Demand valve oxygen appears to be an effective acute treatment for cluster headache. All subjects became headache-free. Time to pain freedom was fast (average 12 minutes). The small number of study subjects does not allow a direct comparison of efficacy between demand valve oxygen and continuous high flow oxygen.

Progress in headache mechanisms and management

In 2010, progress in the headache field was marked by four very different key advances: clarification of the mechanisms of extracephalic allodynia, approval of onabotulinumtoxinA for chronic migraine prophylaxis, validation of combined pharmacological and behavioral treatments for migraine, and establishment of oxygen as an effective acute treatment for cluster headache.

Inhaled Oxygen and Cluster Headache Sufferers in the United States: Use, Efficacy and Economics: Results From the United States Cluster Headache Survey

To present results from the United States Cluster Headache Survey concerning the use of inhaled oxygen as acute treatment for cluster headache (CH). Several small clinic and community-based investigations have indicated that more than 50% of CH patients have never used oxygen for the treatment of their headaches. This statistic is alarming and the reasons why they have not tried oxygen have not been determined. The United States Cluster Headache Survey is the largest study ever completed looking at CH sufferers living in the United States. The total survey consisted of 187 multiple choice questions, 84 questions dealt with oxygen use, efficacy and economics. The survey was placed on a website from October to December 2008. A total of 1134 individuals completed the survey (816 male, 318 female). Among them 868 patients had episodic CH while 266 had chronic CH. Ninety-three percent of survey responders were aware of oxygen as a CH therapy; however, 34% had never tried oxygen. Forty-four percent of patients had to suggest oxygen to their physicians to get prescribed. Twelve percent of physicians refused to prescribe oxygen. Fifty percent using oxygen never received training on proper use. Forty-five percent had to find their own source for oxygen. On prescriptions only 45% specified flow rate, 50% stated CH as diagnosis and 28% indicated mask type. Seventy percent of the surveyed population felt oxygen was effective but only 25% was presently using oxygen. Potential reasons for this finding include: oxygen is slow to onset; prescribed oxygen flow rates are too low for efficacy and most CH patients need to raise flow rates during attacks to achieve response. The efficacy of oxygen does not vary by the age of the patient, gender, the number of CH attacks per day, and smoking history. Episodic CH responds better and faster to inhaled oxygen than chronic CH. Oxygen plus a triptan may be more efficacious and faster at aborting a CH than a triptan alone. Sixteen percent of CH patients state that oxygen is unaffordable while 12% are getting welder grade oxygen because of costs of medical grade oxygen, and this form of oxygen could be potentially dangerous to the individual user. Oxygen is underutilized by CH patients living in the United States. Current recommended oxygen treatment regime is not meeting the needs of many CH patients. Prescribed oxygen flow rates are too low for efficacy. Oxygen can be expensive and very difficult to obtain. Physicians need to be better educated on the use of inhaled oxygen for CH.

Treatment of cluster headache: clinical trials, design and results.

The spontaneous capricious course of cluster headache may give rise to some problems when treatment is being evaluated. This is one of several explanations for there being so few well-designed, randomized, double-blind clinical trials in cluster headache. The standard treatment of acute attacks of cluster headache is inhalation of 100% oxygen. In the prophylaxis of episodic cluster headache, ergotamine, verapamil, lithium, serotonin, inhibitors and steroids are used. In chronic cluster, lithium is the drug of choice, but verapamil may also be tried. Recently, hyperbaric oxygen has been shown to immediately abort acute attacks, and it seems that it may also be useful in the prophylactic treatment. The introduction of the novel 5HT1 agonist sumatriptan as a symptomatic relief of cluster attacks represents further significant progress. Two randomized, double-blind, placebo-controlled, cross-over trials have shown sumatriptan 6 mg sc to be a rapid, effective and well-tolerated acute treatment for cluster headache attacks. Within 15 min of treatment, 74% of attacks on sumatriptan responded compared to 26% of placebo-treated attacks. Functional disability was also significantly improved. Increasing the dose to 12 mg did not offer significantly greater relief compared to sumatriptan 6 mg, but was associated with an increased incidence of adverse events. Interim analysis of 3 months of data from a recent multinational open trial comprising, 138 patients having treated 6353 attacks with subcutaneous sumatriptan 6 mg revealed a headache relief in 96% of attacks treated. There was no evidence of an increased incidence of adverse events with frequent use of sumatriptan. No tachyphylaxis was seen over the 3 months, suggesting that sumatriptan is effective and well tolerated also in long-term acute treatment for cluster headache.

Zolmitriptan Nasal Spray in the Acute Treatment of Cluster Headache: A Meta‐Analysis of Two Studies

To conduct an individual subject meta-analysis of available controlled studies of zolmitriptan nasal spray in the acute treatment of cluster headache. Two double-blind, placebo-controlled, randomized, crossover studies of zolmitriptan nasal spray in the acute treatment of cluster headache, with similar patient populations, protocol designs, doses, and clinical endpoints have been published. In both double-blind studies, each patient was to treat 3 attacks, 1 with placebo, 1 with zolmitriptan 5 mg, and 1 with zolmitriptan 10 mg in a randomized, crossover manner. Headache intensity was rated on a 5-point scale (none to very severe). The primary endpoint was headache relief at 30 minutes post dose: reduction from moderate, severe, or very severe pain to mild or none. A multilevel, random-effects, logistic regression model was used to analyze the data. A total of 121 patients (100 male; 64.5% with episodic cluster headache) provided efficacy data for at least 1 attack. Zolmitriptan 5 mg and 10 mg were significantly more effective at providing headache relief at 30 minutes post treatment than placebo (odds ratio 3.48; 95% confidence interval 1.49-8.10 and odds ratio 8.68; 95% confidence interval: 3.35-22.5, respectively). For episodic cluster headache, response rates were 35.6%, 51.7%, and 73.7% for placebo, zolmitriptan 5 mg (odds ratio 2.5; P = .06 vs placebo), and 10 mg (odds ratio 9.9; P < .001 vs placebo), respectively. For chronic cluster headache, response rates were 17.2%, 41.9%, and 40.7% for placebo, zolmitriptan 5 mg (odds ratio 8.1; P = .035), and 10 mg (odds ratio 7.6; P = .046), respectively. Zolmitriptan was well tolerated in both studies with no serious adverse events reported. Zolmitriptan nasal spray at a dose of 5 mg and 10 mg is efficacious in the acute treatment of episodic and chronic cluster headache.

Zolmitriptan nasal spray in the acute treatment of cluster headache: A double-blind study

In the article “Zolmitriptan nasal spray in the acute treatment of cluster headache: A double-blind study” by …

Zolmitriptan nasal spray in the acute treatment of cluster headache

To evaluate the efficacy and tolerability of zolmitriptan 5 mg and 10 mg nasal spray (ZNS) vs placebo in the acute treatment of cluster headache. Design/ We conducted a multicenter, double-blind, randomized, three-period crossover study using ZNS 5 mg, ZNS 10 mg, and placebo. Headache intensity was rated by a 5-point scale: none, mild, moderate, severe, or very severe. The primary efficacy measure was headache response (pain reduced from moderate, severe, or very severe at baseline, to mild or none) at 30 minutes. Logistic regression was used to account for treatment period effect as well as for cluster headache subtype effect. A total of 52 adult patients treated 151 attacks. For the primary endpoint, both doses reached significance at 30 minutes (placebo = 30%, ZNS 5 mg = 50%, ZNS 10 mg = 63.3%). For headache relief, ZNS 10 mg separated from placebo at 10 minutes (24.5% vs 10%). Zolmitriptan 5 mg separated from placebo at 20 minutes (38.5% vs 20%). For pain-free status, ZNS 10 mg was superior to placebo at 15 minutes (22.0% vs 6%). Both doses had higher pain-free rates than placebo at 30 minutes (placebo = 20%, ZNS 5 mg = 38.5%, ZNS 10 mg = 46.9%). Side effects were mild and seen in 16% of those attacks treated with placebo, 25% of attacks treated with ZNS 5 mg, and 32.7% treated with ZNS 10 mg. Zolmitriptan nasal spray, at doses of 5 and 10 mg, is effective and tolerable for the acute treatment of cluster headache.

Effectiveness of Intranasal Zolmitriptan in Acute Cluster Headache

Cluster headache is a form of primary headache in which attacks are rapid in onset with very severe pain. The mainstays of acute therapy are inhaled oxygen and sumatriptan succinate injection. To evaluate zolmitriptan nasal spray in the acute treatment of cluster headache. Ninety-two patients, aged 40 +/- 10 years (mean +/- SD) (80 men and 12 women), with International Headache Society-defined cluster headache were randomized into a placebo-controlled, double-blind crossover study. Patients treated 3 headache attacks using placebo for 1 attack, 5 mg of zolmitriptan nasal spray (ZNS5) for 1 attack, and 10 mg of zolmitriptan nasal spray for 1 attack. The primary end point was headache relief at 30 minutes, defined as reduction from moderate, severe, or very severe pain to no or mild pain. The study was approved by the appropriate ethics committees. Sixty-nine patients were available for an intention-to-treat analysis. The 30-minute headache relief rates were placebo, 21%; ZNS5, 40%; and ZNS10, 62%. Modeling the response as a binary outcome, the Wald test was significant for the overall regression (chi(2)(1) = 29.4; P<.001), with both ZNS5 and ZNS10 giving significant effects against placebo. Headache relief rates for patients with episodic cluster headache were 30% for placebo, 47% for ZNS5, and 80% for ZNS10, while corresponding rates for patients with chronic cluster headache were 14%, 28%, and 36%, respectively. Zolmitriptan was also well tolerated. Five-milligram and 10-mg doses of zolmitriptan intranasal spray are effective within 30 minutes and well tolerated in the treatment of acute cluster headache. Trial Registration controlled-trials.com Identifier ISCRTN27362692.