The Pathophysiological and Pharmacological Basis of Current Drug Treatment of Migraine Headache

Doodipala Samba Reddy

Disclosures

Expert Rev Clin Pharmacol. 2013;6(3):271-288. 

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Expert Commentary

The profusion of new migraine drugs in the past several years has expanded the therapeutic arsenal and improved pharmacological treatment of migraine.[86,117–126] Nevertheless, the field of migraine therapeutics is still in its infancy. Despite intense efforts in migraine research, the molecular pathophysiology of migraine attacks is poorly understood and remains controversial. Therefore, migraine therapeutics lack the target-based rational therapy to provide migraine control or prevent migraine attacks. The choice of migraine drug or drug combinations for a given patient remains largely empirical. A patient with migraine is started on monotherapy of a NSAID such as ibuprofen, or a combination regimen chosen to relieve the headache by reducing inflammation. The ergot alkaloids provided a foundation of migraine therapeutics. The discovery and development of triptans in 1990s revolutionized the treatment of acute migraine attacks. Triptans are considered safe when used appropriately but are contraindicated for patients with cardiovascular disease, because they are direct coronary vasoconstrictors. The next-generation antimigraine drugs need to improve upon the shortcomings of triptan therapy. Rational polytherapy is emerging with drugs that enhance migraine control when given together (sumatriptan and naproxen sodium). Rational polytherapy presupposes that two drugs with different mechanisms of action may provide better disease control than two drugs with a similar mechanism. Similarly, the adverse effects or toxicity of a drug combination can be additive or synergistic. This may create serious or fatal toxicity, as ergot alkaloids and triptans are powerful vasoconstrictors.

Physicians faced with therapeutic decisions with regard to drug selection have little comparative data that guide prescribing decisions. Abundance of clinical experience with drugs such as sumatriptan and other related triptans has proven to be particularly useful for selection of a triptan for acute migraines. A multicenter database with comparative efficacy and cost-effective analysis would further improve migraine therapeutics. Patients with frequent or severe disabling migraine headaches (two to three attacks per month) should be thoroughly evaluated for a preventive therapy. Such a decision would be useful to reduce the migraine burden and improve the quality of life for many migraine sufferers. Studies from animal models using electrophysiological paradigms indicate that migraine and epilepsy are comorbid episodic disorders that have common pathophysiological mechanisms. Consequently, some antiepileptic drugs such sodium valproate, topiramate and gabapentin are prescribed for migraine prophylaxis. Despite the availability of these prophylactic drugs, there is a huge unmet need for new drugs for improved prophylaxis with fewer side effects. It is hoped that the current research would lead to a major breakthrough for such a compound in the coming decade.

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