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• Increased appetite
• Weight gain

When faced with a decision regarding prophylactic treatment for cluster headache, verapamil is typically the medication of first choice. Doses are slowly increased until the medication takes effect. In the intervening time period, the physician may opt to prescribe corticosteroids, ergot alkaloids, or triptans which are faster acting than verapamil. When an individual medication is not sufficiently effective, the physician may choose to combine two or more drugs for enhanced effect.

When cluster headache does not respond to treatment, it is called refractory cluster headache. Approximately 10-20% of individuals suffering with cluster headache do not respond to first or second-line medication. Some small studies indicate that pizotifen and valproic acid may have a limited effect refractory cluster headache.

Alternative Agents

In addition to the medications mentioned above, there are other agents that have gained popularity due to their effectiveness in relieving cluster headache although they have not been approved by the US Food and Drug Administration for treatment of cluster headache. These include:

• Melatonin
• Capsaicin/Civamide
• Botulinum Toxin A

Melatonin

Melatonin is a hormone that is naturally produced by the body and is actively involved in the sleep cycle. It is the most reliable marker of the circadian rhythm in humans. For unknown reasons, serum levels of melatonin are lower than normal in patients with cluster headaches between cycle periods and, even more so, during a cluster attack. The possibility arises that the reduced level of melatonin may be associated with the development of cluster headache.

Several studies have recently shown that fairly large doses of melatonin can stop cluster attacks. Small clinical trials have shown that approximately 50% of patients with cluster headache taking melatonin achieved remission within 3-5 days. However, the efficacy of melatonin is still a subject of debate, especially for the treatment of refractory cluster headache.

Melatonin can be purchased over-the-counter and appears to have minimal side effects. As yet no specific brand of melatonin can be suggested, although if one brand does not appear to be helping, trying another brand of melatonin may be worthwhile. No one can be sure how much melatonin is actually in each pill or capsule that is sold on the market because melatonin is not regulated by the U.S. Food and Drug Administration. Before starting melatonin, a physician should be consulted.

Capsaicin and Civamide

Capsaicin is a substance found in chili peppers and, when extracted and used medicinally, acts as a neurotransmitter depletory, meaning that it depletes neurotransmitters from the nerve endings which leads to a loss of sensation. Intranasal capsaicin, when administered on the same side as the cluster headache, is effective in aborting the attack but its use is severely limited due to the significant burning and irritation of the tissue that occurs when it is applied. Small trials report that up to 60% of patients participating in those studies found relief from pain.

Civamide is a synthetic form of capsaicin and achieves the same effects with less intense burning and irritation. It is administered intranasally to patients with cluster headache. Though civamide is more promising in terms of comfort, results of efficacy from limited studies have been mixed. Some patients respond initially with a reduction in the number of headaches but after 3 weeks, the drug seems to be less effective.

Botulinum Toxin A