Preventive Treatment Of Migra... Health Article

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The neurotoxin botulinum toxin type A (BTN-A) inhibits the release of the neurotransmitter acetylcholine at the neuromuscular junction, thereby inhibiting striated muscle contractions. However, pain reduction often occurs before the decrease in muscle contractions, indicating an alternative mechanism of action. The antinociceptive effect of BTN-A might be due to the ability of the toxin to block substance P release, as demonstrated using an in vitro culture system. BTN-A blocks the local release of glutamate and substance P in an in vivo model. Furthermore, the production of FOS, a product of the immediate early gene cfos , expressed with neuronal stimuli was prevented upon peripheral exposure to the toxin. These findings indicate that BTN-A blocks peripheral sensitization and indirectly reduces central sensitization. The recent hypothesis that migraine involves both peripheral and central sensitization could help to explain how BTN-A inhibits migraine pain by acting on these two pathways. Oshinsky has shown that injecting BTN-A into the forehead of rodents prevents the central sensitization of wide-dynamic-range neurons in the TNC induced by applying an ‘inflammatory soup’ to the dura [62].

Pericranial BTN-A is effective as a prophylactic treatment of chronic moderate-to-severe migraine [63]. In one trial (0, 25, or 75 U of BTN-A injected symmetrically into glabellar, frontalis and temporalis muscles), the 25-U BTN-A treatment group fared significantly better than did the placebo group, but the 75-U group did not. BTN-A treatment was well tolerated but high-dose BTN-A produced significantly more treatment-related AEs than did placebo. Recent studies indicate that BTN-A is no more effective than placebo at preventing infrequent migraine but is effective at preventing very frequent migraine [64].

Single controlled studies have supported the effectiveness of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor antagonists, riboflavin, coenzyme Q 10 (CoQ 10) and butterroot at preventing episodic migraine. The evidence of effectiveness is better for NSAIDS and conflicted for feverfew [65].

Concluding Remarks

The goals of migraine preventive treatment are to reduce the frequency, duration or severity of attacks, improve responsiveness to acute attack treatment, improve function and reduce disability. It might also prevent the progression of episodic migraine to chronic migraine and result in reductions in the cost of health care. The preventive medications with the best-documented efficacy are the β-blockers, amitriptyline, divalproex and topiramate. Choice of medication is made based on the proven efficacy of a drug, the physician's informed belief about medications not yet evaluated in controlled trials, the AEs of a drug, patient preferences and headache profile, and the presence or absence of coexisting disorders [66].

Coexistent diseases have important implications for treatment. In some instances, two or more conditions can be treated with a single drug. However, this might be the exception rather than the rule. In an effort to use a single medication to treat two conditions, one might select a second- or third-tier choice for either or both conditions, which might not provide adequate treatment for either. Managing two separate illnesses often requires different timelines for assessing drug efficacy. It can take four or six weeks before improvement in migraine attack frequency or severity is measurable. However, hypertension responds to the initiation of, or a change in, treatment within one to two weeks. If individuals have more than one disease, certain categories of treatment might be contraindicated. Although monotherapy is preferred, it is sometimes necessary to combine preventive medications. Patients might require treatment with a ‘therapeutic independence’ approach, wherein each condition is treated separately. This requires one to assess which medication is best suited for each illness independently, and might need multiple physicians or specialists working together to provide optimal treatment recommendations. Controlled trials are needed to determine the true advantage of this combination treatment in episodic and chronic migraine.

New drugs for the preventive treatment of migraine are being developed based in part on an increased understanding of migraine mechanisms. Despite the existence of guidelines for migraine prevention, most patients are not receiving appropriate treatment. With increased awareness and the continued development of new treatment, I believe that more patients will receive appropriate care.

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