Dr. Ron’s Research Review – June 21, 2017

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This week’s research review focuses on subcutaneous histamine for migraine.

Histamine has a selective affinity for H3-receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology.

A randomized, controlled, double-blind 12-week trial of 92 patients compared subcutaneous histamine (1-10 ng twice a week; n = 46) versus oral sodium valproate (500 mg daily dose; n = 46) in migraine prophylaxis. During the 4th, 8th and 12th weeks of treatment histamine caused a significantly greater reduction (P < 0.001) in intensity and duration of migraine attacks as well as in analgesic intake. No difference was detected in the frequency of attacks or in MIDAS.  (Millán-Guerrero et al., 2007)

A 12-week double-blind study of 90 patients compared subcutaneous histamine (1-10 ng twice a week) versus topiramate (100 mg daily dose) in migraine prophylaxis. During the 12 weeks of treatment headache symptoms improved in both the histamine and topiramate groups, which was evident within the first month after the initiation of treatment, with statistically significant (p < 0.001) reductions in headache frequency (50%), Migraine Disability Assessment score (75%), intensity of pain (51%), duration of migraine attacks (45%), as well as in the use of rescue medication (52%).  The present study provides evidence of the efficacy of subcutaneously applied histamine and orally administered topiramate in migraine prophylaxis. (Millán-Guerrero et al., 2008)

A12-week randomized, double-blind study or 100 patients compared subcutaneous histamine (1-10 ng twice a week, n = 50) versus botulinum toxin type A (BoNTA, 50 U one injection cycle, n = 50) in migraine prophylaxis. During the 4th week of treatment there was a significant decrease in all parameters studied, in histamine and BoNTA (P < 0.001). After 4 weeks of treatment, but one injection cycle of 50 U BoNTA had only a 40-day period of efficacy.  This randomized study demonstrated that both histamine and BoNTA are similarly effective and well tolerated in reducing or eliminating headache in migraine prophylaxis. (Millán-Guerrero et al., 2009)

Dr. Ron


 

Articles

Subcutaneous histamine versus sodium valproate in migraine prophylaxis: a randomized, controlled, double-blind study.
            (Millán-Guerrero et al., 2007) Download
Histamine has a selective affinity for H3-receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. The objective of this study was to evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of sodium valproate, in an open clinical trial. Ninety-two patients with migraine were selected under criteria established by the International Headache Society and enrolled in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week; n = 46) compared with oral administration of sodium valproate (500 mg daily dose; n = 46). The variables studied were headache intensity, frequency, duration, analgesic intake and migraine disability assessment (MIDAS). Two-tailed Student's t- test was used to compare means and the Mann-Whitney U and anova tests were used. The data collected during the 4th, 8th and 12th weeks of treatment revealed that histamine caused a significantly greater reduction (P < 0.001) in intensity and duration of migraine attacks as well as in analgesic intake. No difference was detected in the frequency of attacks or in MIDAS. The present study provides evidence of the superior efficacy of histamine applied subcutaneously in migraine prophylaxis when compared with sodium valproate taken orally. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.

Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study.
            (Millán-Guerrero et al., 2008) Download
BACKGROUND:  Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. OBJECTIVE:  To evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of topiramate. METHODS:  Ninety patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) compared with oral administration of topiramate (100 mg daily dose). The variables studied were: headache intensity, frequency, duration, analgesic intake and Migraine Disability Assessment. RESULTS:  The data collected during the 12 weeks of treatment revealed that headache symptoms improved in both the histamine and topiramate groups, which was evident within the first month after the initiation of treatment, with statistically significant (p < 0.001) reductions in headache frequency (50%), Migraine Disability Assessment score (75%), intensity of pain (51%), duration of migraine attacks (45%), as well as in the use of rescue medication (52%). CONCLUSION:  The present study provides evidence of the efficacy of subcutaneously applied histamine and orally administered topiramate in migraine prophylaxis. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.

Subcutaneous histamine versus botulinum toxin type A in migraine prophylaxis: a randomized, double-blind study.
            (Millán-Guerrero et al., 2009) Download
OBJECTIVES:  To compare the efficacy and tolerability of the subcutaneous administration of histamine and botulinum toxin type A (BoNTA) in migraine prophylaxis. BACKGROUND:  Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. METHODS:  One hundred patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) n = 50, compared with administration of 50 U of BoNTA (one injection cycle) n = 50. RESULTS:  The data collected during the 4th week of treatment revealed a significant decrease in all parameters studied, in histamine and BoNTA (P < 0.001). After 4 weeks of treatment, but one injection cycle of 50 U BoNTA had only a 40-day period of efficacy. CONCLUSIONS:  This randomized study demonstrated that both histamine and BoNTA are similarly effective and well tolerated in reducing or eliminating headache in migraine prophylaxis. Low doses of histamine applied subcutaneously may represent a novel and effective therapeutic alternative in migraine patients and lay the clinical and pharmacological groundwork for the use of H3 agonist in migraine prophylaxis.

 

References

Millán-Guerrero, RO, et al. (2007), ‘Subcutaneous histamine versus sodium valproate in migraine prophylaxis: a randomized, controlled, double-blind study.’, Eur J Neurol, 14 (10), 1079-84. PubMed: 17880560
Millán-Guerrero, RO, et al. (2008), ‘Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study.’, Eur Neurol, 59 (5), 237-42. PubMed: 18264012
Millán-Guerrero, RO, et al. (2009), ‘Subcutaneous histamine versus botulinum toxin type A in migraine prophylaxis: a randomized, double-blind study.’, Eur J Neurol, 16 (1), 88-94. PubMed: 19087155