Botulinum toxin type A in chronic migraine.

The use of botulinum toxin type A continues to be investigated by the US FDA for potential use in the treatment of headache. As part of this process there has been extensive research conducted by individual study sites as well as multicenter trials. To date, the majority of the focus has been on migraine headache as well as on tension-type headache. The results of these studies have been mixed. A variety of issues may contribute to the mixed results, including difference in the dose of toxin used, the number of injection sites utilized, the treatment paradigm itself, confounding medications, high and prolonged placebo response, as well as patient selection issues. Currently, the focus on botulinum toxin type A is on those patients who have chronic daily headache with a migraine component to their clinical picture. The results of two large trials in this population produced positive findings, especially when consideration is given to the a priori additional analyses of this complex patient population. The results of these studies have allowed a more focused program to be undertaken in the Phase III evaluation. At the same time, additional work has been performed to understand the mechanism by which botulinum toxin type A may work to alleviate migraine. This work may contribute substantially to improving outcomes with botulinum toxin type A. Characterization of the mechanism of action in pain may be crucial to outcomes because many issues are related to central sensitization.