Abstract
In this issue of Cephalalgia, Silberstein et al. report a trial on the efficacy of botulinum toxin A in chronic tension-type headache (1). This is another important contribution to the growing evidence of the advantages and limitations of botulinum toxin A in headache treatment.
There are now several studies either published or presented at conferences on the efficacy of botulinum toxin A in different primary headache disorders. A number of reports have appeared over the past 10 years on the role of botulinum toxin A for the prophylactic treatment of headache. This started with several positive open trials (for review see (2)). On this basis, placebo-controlled, double-blind trials have been performed for different headache disorders and for different types, doses and injection sites of botulinum toxin A.
Coming now to a preliminary conclusion, it is obvious that in almost all double-blind, placebo-controlled trials on tension-type headache and migraine, the primary end-point was negative from a statistical point of view. In Table 1, all placebo-controlled and double-blind trials that give enough data to conclude on the efficacy of botulinum toxin A are listed. In prophylaxis trials, the comparison between verum and placebo within 3 months should be the basis of the primary efficacy parameter (3, 4). Considering this suggestion, only one trial on migraine in one (the low dose) subgroup fulfilled the criteria of a randomized, double-blind, placebo-controlled trial with a positive primary efficacy parameter for migraine diagnosed according to the International Headache Society criteria. The current study by Silberstein et al. (1) adds to these findings.
Fully published randomized, placebo-controlled, double-blind trials on the efficacy of botulinum toxin A in the prophylactic treatment of idiopathic headache disorders [diagnosis according to International Headache Society (HIS) criteria with at least two digits (e.g. 2.3 chronic tension-type headache)] and with a study design according to IHS guidelines
E + CTTH, Episodic/chronic tension-type headache.
In randomized, placebo-controlled, double-blind trials on defined symptomatic headaches or on the diagnosis of so-called transformed migraine or chronic daily headache (including medication overuse headache), results are more variable. In Table 2, the double-blind, placebo-controlled trials on chronic daily headache and other miscellaneous chronic headache types are presented. In a particular trial programme (5, 6) using day 180 after treatment start for the primary efficacy end-point (i.e. after two injections with 90-day intervals), botulinum toxin A was better than saline at that time point.
Fully published randomized, placebo-controlled, double-blind trials on the efficacy of botulinum toxin A in the prophylactic treatment of symptomatic headache disorders or of chronic migraine/chronic daily headache and with a study design according to International Headache Society guidelines
Primary end-point positive in the subgroup of patients not receiving other prophylactic drugs (5).
CTTH, Chronic tension-type headache.
We think that it is now time to conclude that botulinum toxin A has no role in the prophylactic treatment of episodic infrequent migraine and tension-type headache. However, it remains uncertain whether there may be a role for botulinum toxin A in the treatment of severely affected patients with frequent migraine and/or frequent tension-like headaches; some scientific evidence of efficacy for botulinum toxin A in these patients has been published.
The well-controlled, double-blind, placebo-controlled evaluation of botulinum toxin A for the treatment of migraine and chronic tension-type headache refutes the earlier observations from open-label series. This process is a good example of where an evidence-based approach, despite a long period where only open-label studies were published, is better able to distinguish the scientific basis for the appropriate use of botulinum toxin A for the prophylaxis of migraine and tension-type headache.
Summing up, this should be the end of the road for the use of botulinum toxin A in episodic migraine and tension-type headache. Whether further trials in severely affected patients with mixed headaches are warranted and what the results of such trials might tell us must be discussed after the publication of ongoing trials on these headache syndromes.