PDF: Intranasal Zolmitriptan in Acute Cluster Headache
(2006)Objective
Zolmitriptan - To evaluate the efficacy and tolerability of 5 mg and 10 mg doses of intranasal zolmitriptan for the treatment of cluster headache.
Study Summary
• The 10 mg dose was more effective and the treatment effect was substantially greater in patients with episodic cluster headache than in chronic cluster headache.
Intervention
A crossover design where patients with cluster headache treated three separate attacks, each with a single intranasal dose of either placebo, 5 mg zolmitriptan, or 10 mg zolmitriptan.
Study Design
Arms: 3-way crossover (each patient treated 3 attacks, >=24h apart): Zolmitriptan 5 mg nasal spray (65 attacks), Zolmitriptan 10 mg nasal spray (63 attacks), Placebo nasal spray (61 attacks); N=92 randomized, 69 treated >=1 attack (ITT)
Outcome
• Pain-free rates at 30 minutes were 16% for placebo, 28% for 5 mg, and 50% for 10 mg.
• Efficacy was substantially higher in episodic cluster headache (80% relief with the 10 mg dose) than in chronic cluster headache (36% relief with the 10 mg dose).
Bottom Line
Both 5 mg and 10 mg doses of intranasal zolmitriptan are effective and well-tolerated for the acute treatment of cluster headache, providing significant headache relief within 30 minutes. The 10 mg dose was more effective than the 5 mg dose, and the benefit was much more pronounced in patients with episodic versus chronic cluster headache.
Major Points
- This was a randomized, double-blind, 3-attack crossover study involving 92 patients with International Headache Society-defined cluster headache.
- Each patient treated 3 separate attacks, one with intranasal placebo, one with 5 mg zolmitriptan nasal spray (ZNS5), and one with 10 mg zolmitriptan nasal spray (ZNS10).
- The primary endpoint was headache relief (pain reduced from moderate/severe/very severe to mild/none) at 30 minutes.
- Headache relief at 30 minutes was achieved in 21% of placebo-treated attacks, 40% with ZNS5, and 62% with ZNS10. Both active doses were significantly superior to placebo (P<.001).
- The treatment effect was substantially greater in patients with episodic cluster headache (80% relief with ZNS10) compared to those with chronic cluster headache (36% relief with ZNS10).
- The treatment was well tolerated, with no serious adverse events reported.
Study Design
- Study Type
- Randomized, double-blind, 3-attack crossover study
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 92
- Follow-up
- Patients treated 3 attacks, with each attack being a treatment period.
- Centers
- 5
- Countries
- Germany, Italy, United Kingdom
Primary Outcome
Definition: Headache relief at 30 minutes, defined as a reduction in headache pain from moderate, severe, or very severe to no or mild pain.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 21% | 40% with 5 mg dose; 62% with 10 mg dose | - | <.001 |
Limitations & Criticisms
- The study was conducted at specialist headache centers, which may limit the generalizability of the results to a broader patient population.
- A significant number of patients (23 out of 92) were not included in the final intention-to-treat analysis for various reasons, including ending their cluster bout or being lost to follow-up.
Citation
Arch Neurol. 2006;63:1537-1542