Baclofen,
tizanidine and
botulinum toxin A, agents used to treat disorders of muscle tone, have been studied as potential preventative treatments for
migraine,
tension-type headache and other related disorders. The most extensive work has been completed with
botulinum toxin A. However, there is still a paucity of well controlled, clinical trials with this agent, and overall there have been conflicting and oftentimes equivocal results: studies of its use in
migraine headache have suggested efficacy, whereas those of
tension-type headache have not shown significant evidence of efficacy. There were few significant adverse events associated with the use of
botulinum toxin A in these trials. The mechanism by which
botulinum toxin A may work to prevent
headache is not clear. Although changes in muscle tone may play a role in the effect of the
drug, central mechanisms such as effects on
neuropeptides involved in the pathogenesis of
migraine may also be relevant. Further clinical trial work is in progress to help determine optimal administration schedules and choice of injection locations with
botulinum toxin A for specific
headache disorders. There has been limited study of the use of
baclofen, an agent that acts centrally via
GABA(A) receptors, in
migraine and
cluster headache, with only two open trials conducted to date. Both of these studies support the use of
baclofen in the preventive treatment of
headache.Tizanidine, which may have both a peripheral and a central mechanism in the locus ceruleus in
migraine headache, has been studied in several clinical trials. Although the primary mechanism of action of this agent is, like
clonidine, as an alpha-
adrenoceptor agonist, it has little
antihypertensive effect. Open trials of
tizanidine have shown it to be useful in
chronic headache. One well controlled trial, conducted as a follow-up to an open-label trial in the preventive treatment of
chronic daily headache, reported
tizanidine as having a statistically significant benefit over placebo. Also of interest is its use in conjunction with a long-acting
NSAID to aid in the treatment of rebound
headache accompanying the discontinuation of overused acute
migraine therapies. In conclusion, though limited, the studies suggest the efficacy of
botulinum toxin A,
baclofen and
tizanidine in
primary headache disorders.