Headache. 2015 Mar 31.

Clomiphene Citrate as a Preventive Treatment for Intractable Chronic Cluster Headache: A Second Reported Case With Long-Term Follow-Up.

Rosen, T.D.
Author information1Geisinger Health System, Department of Neurology, Geisinger Headache Clinic, Wilkes-Barre, PA, USA.
Abstract
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.
© 2014 American Headache Society.

PMID:25828543[PubMed]
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Acta Clin Croat. 2009 Sep;48(3):311-4.

Gabapentin in the prophylaxis of cluster headache: an observational open label study.
Vukovic V1, Lovrencic-Huzjan A, Budisic M, Demarin V.
Author information University Department of Neurology, Reference Center for Neurovascular Disorders, Ministry of Health, Republic Croatia, Sestre milosrdnice University Hospital, Zagreb, Croatia. vlasta.vukovic@uclmail.net

Abstract
Cluster headache is an extremely painful syndrome that occurs more frequently in men. Although periodic in most cases, cluster headache has a considerable impact on the patient quality of life. Acute therapy is usually not sufficient and most patients warrant prophylactic treatment. The aim of this study was to evaluate the efficacy and safety of gabapentin as prophylaxis in patients with cluster headache previously successfully or unsuccessfully treated with other prophylactic medications. The study included 14 patients, 9 men and 5 women (mean age 42 +/- 15 years). Gabapentin was gradually introduced; the maintenance dose was in the range from 900 mg to 2400 mg: 900 mg/day in 6, 1200 mg/day in 2, 1800 mg/day in 4 and 2400 mg/day in 2 patients. The mean duration of treatment was 3.5 (range 2-5) months. Within 1-2 weeks, patients reported response to treatment. The mean number of headache days/4 weeks was reduced from 378 (mean 27) at baseline to 210 (mean 15) at the end of follow up, yielding a reduction by 12 headache days/4 weeks or by 44.94% in headache frequency. Pain intensity was decreased by 25% in 1 (7.14%) patient, by 50% in 8 (57.14%) and by 75% in 3 (21.4%) patients, whereas 2 (14.28%) patients were non-responders. Upon completion of gabapentin therapy, there were no recurrent in treated patients. Adverse events were reported in 8/14 (57.14%) patients and were generally of mild to moderate severity. The most frequently reported adverse events were drowsiness, dizziness, slowness and constipation. There were no drop-outs due to adverse events.
PMID:20055254[PubMed]
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Eur J Neurol. 2007 Jun;14(6):694-6.
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The use of gabapentin in chronic cluster headache patients refractory to first-line therapy.

Schuh-Hofer S, Israel H, Neeb L, Reuter U, Arnold G.

Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.sigrid.schuh-hofer@gmx.net

Chronic cluster headache (CCH) is a rare but challenging condition. About 20% of CCH patients get refractory to treatment. Gabapentin has recently been reported to be efficacious in the treatment of CCH. To test the potential of gabapentin as second-line drug, we prospectively studied the efficacy of gabapentin as add-on drug in eight patients suffering from CCH refractory to first-line treatment. Six of eight CCH patients responded to treatment. After the end of the study phase, the patients' clinical course was further followed up until January 2006. The longest period of being continuously pain-free under gabapentin treatment was 18 months. In some individuals, increasing doses were needed with time. We conclude that gabapentin may be offered as treatment trial in patients refractory to first-line treatment. However, patients may fail to respond to treatment and drug tolerance may occur with time.

PMID: 17539953 [PubMed