title: Intranasal civamide for the treatment of episodic cluster headaches.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of intranasal civamide solution for preventive treatment during an episodic cluster headache period.
  
  
  METHODS
  This was a multicenter, double-blind, randomized, vehicle-controlled study with a 7-day treatment period and a 20-day posttreatment period performed at 14 headache/neurology centers in the United States. Twenty-eight subjects were randomized to receive civamide or its vehicle in a 2:1 ratio; 18 received civamide and 10 received the vehicle. Subjects received 100 microL of 0.025% civamide (25 microg) or 100 microL of the vehicle to each nostril via dropper once daily for 7 days. The total daily dose of civamide was 50 microg.
  
  
  METHODS
  The number of cluster headaches per week during the treatment and posttreatment periods, pain intensity, presence of associated symptoms, and the incidence of adverse events were assessed.
  
  
  RESULTS
  Subjects in the civamide group had a significantly greater percent decrease in the number of headaches from baseline to posttreatment during days 1 through 7 (-55.5% vs -25.9%; P =.03) and a trend toward significance during days 8 through 14 (-66.9% vs -32.3%; P =.07) and days 15 through 20 (-70.6% vs -34.9%; P =.07), as well as a near-significant decrease during the entire posttreatment period (days 1 through 20 [P =.054]) compared with the vehicle group. There were larger decreases in the number of headaches per week during the posttreatment period in the civamide-treated group, with trends toward significance during posttreatment days 8 through 14 (-8.6 vs -3.6; P =.09) and days 15 through 20 (-8.9 vs -3.6; P =.07). There were no significant differences between groups in cluster headache pain intensity, number of severe headaches, or associated symptoms. The most common adverse events included nasal burning (14 of 18 civamide-treated subjects, 1 of 10 vehicle-treated subjects; P =.001) and lacrimation (9 of 18 civamide-treated subjects, 0 of 10 vehicle-treated subjects; P =.01).
  
  
  CONCLUSIONS
  Intranasal civamide solution at a dose of 50 microg may be modestly effective in the preventive treatment of episodic cluster headache.
authors.affiliation: Michigan Headache Pain and Neurological Institute, 3120 Professional Dr, Ann Arbor, MI 48104, USA.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Saper
authors.forename: Jack
authors.initials: J
authors.lastname: Klapper
authors.forename: Ninan T
authors.initials: NT
authors.lastname: Mathew
authors.forename: Alan
authors.initials: A
authors.lastname: Rapoport
authors.forename: Scott B
authors.initials: SB
authors.lastname: Phillips
authors.forename: Joel E
authors.initials: JE
authors.lastname: Bernstein
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002211:Capsaicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D003027:Cluster Headache / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012646:Self Administration / Q000706:statistics & numerical data; D018709:Statistics, Nonparametric
chemical_list: D000889:Anti-Arrhythmia Agents; C117479:zucapsaicin; D002211:Capsaicin