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SYNOPSISPatients with chronic cluster headache refractive to agents such as lithium carbonate, methysergide, corticosteroids, or thecalcium channel blocking agents, may respond to histamine desensitization. Intravenous histamine phosphate administeredover a 10-day treatment course in combination therapy with prophylactic agents, including H 1 and H 2 antagonists, may resultin a marked improvement in the frequency of cluster attacks. Sixty-four patients seen at the Diamond Headache Clinic wereadmitted to the Inpatient Headache Unit at Louis A. Weiss Memorial Hospital and followed for a period up to one year afterdischarge. Twenty-five patients had at least a 75% reduction in cluster attacks and all but nine patients demonstrated a partialreduction in their clusters. A group of patients who were previous treatment failures with established agents for chroniccluster were retreated with the same agent following histamine desensitization and had a significant improvement in theircluster attacks.Another group of patients responded to local application of 5% or 10% cocaine solution to the sphenopalatine ganglion. Whileuseful for some patients, the results did not achieve statistical significance compared to similarly treated patients who did notreceive cocainization of the sphenopalatine ganglion.