No abstract

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.

No abstract

Recently, the endocannabinoid system was discovered, which consists of receptors, ligands and enzymes that are widely expressed in the brain and the periphery (Table 1), where they act to maintain balance in several homeostatic processes. 7,8

I congratulate Drs. Mathew and Dodick and their associates for attempting the best and largest double-blind clinical trial of botulinum toxin for the treatment of chronic daily headache. 1,2 First, they identified placebo responders in the initial 30-day single-blind study. Then, with a double-blind protocol, they evaluated the response to botulinum toxin or placebo in the placebo responsive group and the nonplacebo responders. For one thing, the studies showed that people who did not exhibit a placebo response on one occasion did so in other occasions. Presumably, the opposite also applies. The results in favor of botulinum toxin therapy appear impressive. Although a statistically significant difference between the effects of botulinum toxin versus placebo was noted only at 1 or 2 time points, in the analysis of a decrease from baseline of 50% or more headache days per 30-day period, there was a consistent numerical advantage favoring botulinum toxin at every 30-day time point.I believe the results and conclusions were flawed by the old bugaboos, the placebo/nocebo factors. Seventy-eight percent of patients "correctly guessed" that they had received the placebo during the run in period. The percentage of patients correctly "guessing" the treatment was 70%, 65%, and 60% after the first, second, and third treatments, respectively. The authors claimed that "This does not greatly differ from 50%, which would be the expected accuracy of guess by chance. . ." But guessing an active agent versus the placebo in a typical double-blind study is different than looking in a mirror and recognizing whether one has received botulinum toxin or not. The 60% to 70% who recognized (my interpretation) that they had received the active agent or placebo rather than "correctly guessed" had an expectation of improvement or an expectation of no improvement (nocebo); they had effectively unmasked their part in the study. Those who recognized that they had received botulinum toxin had an expectation of improvement, raising the overall positive response numbers. Those who recognized that they had not received the active agent had the expectation of no benefit, the nocebo effect, lowering the placebo nonresponder numbers. Those who guess active therapy or placebo in a truly double-blind study do not have these expectations. Or if they have an expectation it is weak, because of uncertainty, and likely to be wrong 50% of the time. It is the expectations of those who recognized the active agent or placebo that, in my opinion, would account for the difference between the 2 groups in these studies.I recommend an analysis of the 30% to 40% who did not guess/recognize the type of treatment they received. I suspect this analysis would not show the differences reported in these studies.In addition to the unblinding of the patient, I suspect that the doctors administering the second and third courses of injections were not fully blinded. I presume they were blinded with regard to the agents in the syringes, but how could they be blinded to the appear...