Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study

Arch Neurol. 2006 Nov;63(11):1537-42. doi: 10.1001/archneur.63.11.nct60002. Epub 2006 Sep 11.


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 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.

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. Trial Registration controlled-trials.com Identifier ISCRTN27362692.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Administration, Intranasal*
  • Adolescent
  • Adult
  • Aged
  • Cluster Headache / complications
  • Cluster Headache / drug therapy*
  • Cohort Studies
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Evaluation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxazolidinones / therapeutic use*
  • Serotonin Receptor Agonists / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Tryptamines / therapeutic use*


  • Oxazolidinones
  • Serotonin Receptor Agonists
  • Tryptamines
  • zolmitriptan

Associated data

  • ISRCTN/ISRCTN27362692