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

Doodipala Samba Reddy


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

In This Article

Diagnosis of Migraine

The diagnosis of a headache is based on clinical features, most notably the presence or absence of aura in migraine. The International Headache Society has established accepted guidelines for diagnosis (Table 1).[13,46] There are two common types of migraine headaches; MA and MO. However, there are other migraine types and variants observed in some patients. There are typical characteristics for migraine headaches. For diagnosis of migraine, the most usual features are photophobia, phonophobia and nausea in 85% of patients, vomiting in 50%, osmophobia and kinesiophobia. Prodrome, which is usually represented by mood changes, and aura must be distinguished. There may be a postdrome of ongoing mood change in some. In contrast to tension-type headaches, which tend to be bilateral, migraine headaches are usually unilateral. Migraine headaches may become bilateral during the course of the headache and are intensified by routine activity. There is a need to distinguish between infrequent migraine (<10/month), frequent migraine (10–14/month) and chronic migraine or chronic daily headache (15+ headaches/month), with at least eight headaches being migraine. Frequent migraine and chronic daily headache are the most likely subjects to appear for medical consultation and therapy (Box 2). Chronic migraine is defined as headaches in the absence of medication overuse, occurring more than 15 days per month for more than 3 months, of which headaches on 8 days or more must fulfill the criteria for migraine.[46]

Migraine Stages

The clinical presentation of migraine is defined in three stages: the preheadache (premonitory and aura) phase, the headache phase and resolution phase. In the preheadache phase, the premonitory phases may precede the headache by hours to days. The migraine aura manifests with more focal neurological symptoms, commonly described as various visual-field changes. These symptoms usually precede the headache by 5–20 min and lasts up to 1 h. In many patients with migraines, the headache phase is characterized by migraine pain that is generally a throbbing, pulsatile pain in the frontotemporal region. In contrast to migraine, patients with tension headaches present dull or pressing pain involving the entire head. The duration of migraine attacks varies from patient to patient, but ranges from hours to days (from 4 to 72 h). The migraine attack intensity and attack frequency are independent features. As illustrated in Figure 1, other pathophysiological symptoms that accompany the headache phase include gastrointestinal symptoms such as nausea and vomiting, and autonomic symptoms such as nasal congestion and lacrimation. The resolution phase occurs after the attack and usually results in symptoms of fatigue and irritability for 1–2 days, which may be referred to as 'migraine hangover'.

Migraine Intensity

For the purpose of treatment considerations, migraine attacks can be classified into three categories: mild migraine (occasional throbbing headache and no major functional impairment), moderate migraine (moderate or severe headache, some impairment of functioning and nausea) and severe migraine (more than three migraines in a month, significant functional impairment, and marked nausea and vomiting).

Menstrual Migraine

Women are more commonly affected by migraine. Neuroendocrine events related to reproductive stages and to the menstrual cycle affect the occurrence of migraines. In many women with migraines, migraine attacks fluctuate in relation to their menstrual cycle, most frequently around menstruation. This hormone-related migraine is often referred to as 'menstrual migraine'.[47–54] During regular menstrual cycles, the most common times of migraine attacks are 2 days before onset of menses or the first 2 days of menses. Attacks occur on day 1 ± 2 (i.e., days -2 to +3) of menstruation in at least two out of three menstrual cycles and additionally at other times of the cycle (the first day of menstruation is day 1 and the preceding day is day-1; there is no day 0). For the purposes of diagnosis, menstruation is considered to be endometrial bleeding resulting from either the normal menstrual cycle or from the withdrawal of exogenous progestogens, as in the case of combined oral contraceptives and cyclical hormone replacement therapy. In general, menstrual migraine is more severe than migraines that occur at other times, may persist longer, occurs more frequently and is more resistant to therapy. Menstrual migraine attacks respond well to acute treatment with triptans – naratriptan and frovatriptan.[50,54–58] Oral contraceptives/hormone replacements may exacerbate migraines.