What is the role of melatonin in the management of cluster headaches?

Melatonin's Role in Cluster Headaches

Melatonin may be effective for the prevention of episodic cluster headaches, with evidence showing reduced attack frequency in some patients, though it is not a first-line treatment option. 1

Mechanism and Rationale

Melatonin's potential effectiveness in cluster headaches appears to be related to several mechanisms:

• Altered melatonin levels have been documented in cluster headache patients 2
• Cluster headaches characteristically occur at night during the first REM sleep phase, suggesting a circadian rhythm component 3
• Melatonin has anti-inflammatory effects, scavenges free radicals, reduces proinflammatory cytokines, and inhibits nitric oxide synthase activity 2
• It may help regulate neurovascular function and modulate serotonin, both relevant to headache pathophysiology 2

Evidence for Effectiveness

The evidence for melatonin in cluster headaches is limited but promising:

• A double-blind placebo-controlled pilot study found that melatonin 10 mg significantly reduced headache frequency in episodic cluster headache patients 1
• 50% of treated patients were responders, with attack frequency declining 3-5 days after treatment initiation 1
• Case reports have shown that melatonin may be effective even in some chronic cluster headache patients 3
• Ramelteon, a selective melatonin MT1/MT2 receptor agonist, has been reported to completely suppress cluster headache attacks during sleep in a case report 4

Treatment Algorithm for Cluster Headaches

First-line treatments (according to guidelines):

1. Abortive treatments:

   • Subcutaneous sumatriptan (6 mg) or intranasal zolmitriptan (10 mg) 5
   • Normobaric oxygen therapy 5

2. Preventive treatment for episodic cluster headache:

   • Galcanezumab (recommended in guidelines) 5

When to consider melatonin:

• As an adjunctive treatment when first-line treatments are insufficient
• For patients who cannot tolerate other preventive medications
• Particularly for patients with predominantly nocturnal attacks
• For patients with comorbid sleep disorders

Dosing and Administration

• Typical dosage: 10 mg daily taken in the evening 1
• Response typically begins 3-5 days after treatment initiation 1
• Limited side effect profile makes it well-tolerated compared to other preventive medications
• Consider using melatonin with USP Verification Mark for consistent dosing 5

Important Caveats

• Response rate is relatively low (approximately 50% in studied populations) 1
• Less effective for chronic cluster headache compared to episodic cluster headache 1
• Not FDA-regulated in the US, leading to potential variations in product quality 5
• Common side effects may include daytime sleepiness, headache, and gastrointestinal upset 5
• Current guidelines do not specifically recommend melatonin for cluster headaches, focusing instead on other treatments 5

Monitoring and Follow-up

• Assess response after 2 weeks of consistent use
• If effective, continue through the expected cluster period
• Monitor for side effects including morning headache, morning sleepiness, and rarely delusions/hallucinations 5
• Consider combination with conventional treatments if partial response

While melatonin shows promise for some patients with cluster headaches, particularly those with episodic cluster headaches and nocturnal attacks, it should be considered as a complementary approach rather than replacing established first-line treatments that have stronger evidence and guideline support.