Effectiveness of Intranasal Zolmitriptan in Acute Cluster Headache

Abstract

Background: 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. Objective: To evaluate zolmitriptan nasal spray in the acute treatment of cluster headache. Methods: 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. Results: Sixty-nine patients were available for an intentionto-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 (2 1 =29.4; PϽ.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. Conclusion: 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.

Evaluation of guideline-adherent treatment in cluster headache

“…The ratings of subjective efficacy were similar to the data from clinical trials, e.g. an excellent efficacy of subcutaneous sumatriptan (18) and a moderate to excellent efficacy of nasal sumatriptan (19), which is not approved in Germany for cluster headache, or zolmitriptan (20). With respect to preventive treatment, only verapamil and steroids received sufficient efficacy.…”

Evaluation of guideline-adherent treatment in cluster headache

“…The ratings of subjective efficacy were similar to the data from clinical trials, e.g. an excellent efficacy of subcutaneous sumatriptan (18) and a moderate to excellent efficacy of nasal sumatriptan (19), which is not approved in Germany for cluster headache, or zolmitriptan (20). With respect to preventive treatment, only verapamil and steroids received sufficient efficacy.…”

Effects of acute and preventive therapies for episodic and chronic cluster headache: A scoping review of the literature

“…A PRISMA flow diagram that summarized the process of study selection is presented in Figure 1. After an initial review of 3488 citations (following removal of duplicates), a total of 56 studies 18–72 were selected for inclusion. These studies included 45 published RCTs, four RCTs that were available only in clinical trial registries, 57,61–63 and seven observational studies, 66–72 with publication dates from 1978 to 2021.…”

“…As none of the studies included in this review reported individual end points for the subgroups of patients diagnosed with chronic or episodic CH, the results presented were based on a comparison of the combined subtype groups versus control. Outcomes from the following acute treatment interventions were evaluated: Dihydroergotamine (DHE) nasal spray (ns; n = 2) 20,65 ; Triptans ( n = 7) 22,24,28,29,37,48,54 including zolmitriptan ns, sumatriptan subcutaneous (sc), and sumatriptan ns; Low flow 31 or high flow 25 oxygen ( n = 5), comparisons of low versus high level flow, 18 and new modes of delivery including demand valve oxygen (DVO) 47,60 ; Noninvasive vagal nerve stimulation (nVNS; n = 2) 27,52 ; Invasive sphenopalatine ganglion (SPG) stimulation ( n = 2) 34,51 ; Somatostatin ( n = 1), 65 related formulations ( n = 1), 43 and pasireotide ( n = 1) 57 ; Lidocaine/cocaine ( n = 1) 26 ; Hyperbaric oxygen ( n = 1) 59 …”

Cluster headache in Asian populations: Similarities, disparities, and a narrative review of the mechanisms of the chronic subtype

“…Medications commonly used to treat CH attacks show differential responses in patients with eCH and cCH. Patients with cCH are less likely to respond to triptan ( 21 , 57 ). Some studies show a differential response to lithium as a preventive medication in patients with cCH compared to those with eCH.…”

Evaluation of guideline-adherent treatment in cluster headache

“…The ratings of subjective efficacy were similar to the data from clinical trials, e.g. an excellent efficacy of subcutaneous sumatriptan (18) and a moderate to excellent efficacy of nasal sumatriptan (19), which is not approved in Germany for cluster headache, or zolmitriptan (20). With respect to preventive treatment, only verapamil and steroids received sufficient efficacy.…”

Effects of acute and preventive therapies for episodic and chronic cluster headache: A scoping review of the literature

“…A PRISMA flow diagram that summarized the process of study selection is presented in Figure 1. After an initial review of 3488 citations (following removal of duplicates), a total of 56 studies 18–72 were selected for inclusion. These studies included 45 published RCTs, four RCTs that were available only in clinical trial registries, 57,61–63 and seven observational studies, 66–72 with publication dates from 1978 to 2021.…”

“…As none of the studies included in this review reported individual end points for the subgroups of patients diagnosed with chronic or episodic CH, the results presented were based on a comparison of the combined subtype groups versus control. Outcomes from the following acute treatment interventions were evaluated: Dihydroergotamine (DHE) nasal spray (ns; n = 2) 20,65 ; Triptans ( n = 7) 22,24,28,29,37,48,54 including zolmitriptan ns, sumatriptan subcutaneous (sc), and sumatriptan ns; Low flow 31 or high flow 25 oxygen ( n = 5), comparisons of low versus high level flow, 18 and new modes of delivery including demand valve oxygen (DVO) 47,60 ; Noninvasive vagal nerve stimulation (nVNS; n = 2) 27,52 ; Invasive sphenopalatine ganglion (SPG) stimulation ( n = 2) 34,51 ; Somatostatin ( n = 1), 65 related formulations ( n = 1), 43 and pasireotide ( n = 1) 57 ; Lidocaine/cocaine ( n = 1) 26 ; Hyperbaric oxygen ( n = 1) 59 …”

Cluster headache in Asian populations: Similarities, disparities, and a narrative review of the mechanisms of the chronic subtype

“…Medications commonly used to treat CH attacks show differential responses in patients with eCH and cCH. Patients with cCH are less likely to respond to triptan ( 21 , 57 ). Some studies show a differential response to lithium as a preventive medication in patients with cCH compared to those with eCH.…”

Evaluation of guideline-adherent treatment in cluster headache

“…The ratings of subjective efficacy were similar to the data from clinical trials, e.g. an excellent efficacy of subcutaneous sumatriptan (18) and a moderate to excellent efficacy of nasal sumatriptan (19), which is not approved in Germany for cluster headache, or zolmitriptan (20). With respect to preventive treatment, only verapamil and steroids received sufficient efficacy.…”

Effects of acute and preventive therapies for episodic and chronic cluster headache: A scoping review of the literature

“…A PRISMA flow diagram that summarized the process of study selection is presented in Figure 1. After an initial review of 3488 citations (following removal of duplicates), a total of 56 studies 18–72 were selected for inclusion. These studies included 45 published RCTs, four RCTs that were available only in clinical trial registries, 57,61–63 and seven observational studies, 66–72 with publication dates from 1978 to 2021.…”

“…As none of the studies included in this review reported individual end points for the subgroups of patients diagnosed with chronic or episodic CH, the results presented were based on a comparison of the combined subtype groups versus control. Outcomes from the following acute treatment interventions were evaluated: Dihydroergotamine (DHE) nasal spray (ns; n = 2) 20,65 ; Triptans ( n = 7) 22,24,28,29,37,48,54 including zolmitriptan ns, sumatriptan subcutaneous (sc), and sumatriptan ns; Low flow 31 or high flow 25 oxygen ( n = 5), comparisons of low versus high level flow, 18 and new modes of delivery including demand valve oxygen (DVO) 47,60 ; Noninvasive vagal nerve stimulation (nVNS; n = 2) 27,52 ; Invasive sphenopalatine ganglion (SPG) stimulation ( n = 2) 34,51 ; Somatostatin ( n = 1), 65 related formulations ( n = 1), 43 and pasireotide ( n = 1) 57 ; Lidocaine/cocaine ( n = 1) 26 ; Hyperbaric oxygen ( n = 1) 59 …”

Cluster headache in Asian populations: Similarities, disparities, and a narrative review of the mechanisms of the chronic subtype

“…Medications commonly used to treat CH attacks show differential responses in patients with eCH and cCH. Patients with cCH are less likely to respond to triptan ( 21 , 57 ). Some studies show a differential response to lithium as a preventive medication in patients with cCH compared to those with eCH.…”