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Melatonin in Cluster Headache

Rationale for Use and Possible Therapeutic Potential

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Summary

Cluster headache is an excruciatingly painful, essentially unilateral headache associated with homolateral autonomic signs. It has a highly distinctive temporal pattern. The attacks occur in cluster periods lasting weeks or months that are separated by remission periods of months or years. The pathogenesis of cluster headache is still unknown, although it is probable that the pain and autonomic manifestations result from the activation of the trigeminovascular system.

The periodic nature of cluster headache [i.e. typically, cluster periods begin in spring or autumn (fall) when there is a rapid rate of change of the quantity of daylight, and, often, within a cluster period, the attacks recur on a daily basis with ‘clockwork’ regularity] suggests that activation of the trigeminovascular system could derive from the involvement of the hypothalamus, the site of the biological pacemaker.

Since melatonin production is under the control of the hypothalamic pacemaker, the role of melatonin in cluster headache has been investigated. A number of studies have shown that melatonin levels are reduced during cluster periods, suggesting that the disorder is associated with a periodic dysfunction of hypothalamic structures.

In this article, some of the biological functions of melatonin are reviewed in light of their possible relevance to the mechanisms that cause cluster headache. These include the role of melatonin in the regulation of circadian rhythms and the possible implications of its effects on γ-aminobutyric acid (GAB A) and serotonin (5-hydroxytryptamine; 5-HT) receptors, intracellular levels of calcium ions and prostaglandin production. Preliminary clinical data on the use of melatonin in the prophylaxis of cluster headache are discussed. In a double-blind, placebo-controlled clinical study, melatonin effectively prevented cluster headache in 50% of patients. This finding suggests the possible utility of melatonin as a second-line prophylactic agent, and provides additional evidence of a periodic central dysfunction in this disease.

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  1. Istituto Nazionale Neurologico Carlo Besta, via Celoria 11, 20133, Milan, Italy

    Massimo Leone & Gennaro Bussone

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  1. Massimo Leone
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Leone, M., Bussone, G. Melatonin in Cluster Headache. Mol Diag Ther 9, 7–16 (1998). https://doi.org/10.2165/00023210-199809010-00002

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