Clomiphene citrate as a preventive treatment for intractable chronic cluster headache: A second reported case with long-term follow-up

Objective To describe a second case of treatment refractory chronic cluster headache responsive to clomiphene citrate and with long-term follow-up. Methods Case report with 7-year evaluation. Case A 63-year-old man with a 17-year history of chronic cluster headache preceded to have significant adverse events or was nonresponsive to multiple cluster headache preventive medications including verapamil, lithium, valproic acid, topiramate, baclofen as well as greater occipital nerve blocks and inpatient hospitalization. The patient experienced 3-5 headaches per day. On clomiphene citrate 100 mg/day he became 100% pain-free and remained so for 3.5 years with only mild fatigue as a side effect. He then had cluster headache recurrence and did well on gabapentin for another 3 years with repeat headache recurrence. Clomiphene was restarted, and he became pain-free once again. Discussion This is the second reported case of the effective use of clomiphene citrate for the preventive treatment of medicinal refractory chronic cluster headache. This is the first case to report long-term follow-up of this neurohormonal treatment. Clomiphene citrate appears to be safe for extended use in chronic cluster headache even in an elderly sufferer and has a minimal side effect profile. The mechanism of action of how clomiphene prevents cluster headache may involve both its ability to enhance testosterone production and its ability to bind to hypothalamic estrogen receptors. Clomiphene citrate should join the list of alternative cluster headache prophylactic treatments to be considered by headache specialists when conventional cluster headache preventives are ineffective.