Assessment of Illness Severity (cont.)

---

In evaluating these three treatment strategies, a single treatment is unlikely to be optimal for all attacks in each patient, due to the heterogeneity of migraine attacks.^[2] Step-care is clearly not an option for this situation. To overcome this problem, a combination of stratified and staged care may work best. If the patient has access to a selection of medications, they can choose one appropriate to the severity of the presenting attack. Migraine sufferers can often predict the severity of an approaching attack based on their prior knowledge of premonitory symptoms.^[17]

In this scheme, the physician assesses the severity of the migraine, and provides the patient with a range of medications, from simple analgesics to triptans. The patient then takes a triptan if the presenting attack is moderate-to-severe, and an analgesic product (monotherapy, or in combination with another drug) if it is mild-to-moderate. If either of these medications fails, the patient has rescue medication that they can take (usually an initial or alternative triptan, or a different triptan formulation, depending on the initial therapy). Such a scheme provides each patient with effective medications, and helps to ensure their use in a cost-effective way. The end result is individualised care that is patient focused, and cost-effective.

It is therefore useful to divide patients into those with mild-to-moderate and those with moderate-to-severe migraine and treat according to the defined severity of illness (Table 4).

Acute Treatments. Many different drugs are used in the UK as acute treatments for migraine, from simple analgesics to migraine-specific medications. The Duke database has captured evidence-based data on their clinical profiles, as summarised in Table 5.

Proven effective therapies for patients with mild-to-moderate migraine include aspirin and NSAIDs in high doses, analgesic-anti-emetic combinations and isometheptene-analgesic combinations. The triptans are effective therapies for patients with moderate-to-severe migraine.^[15] All the available triptan drugs are effective and well-tolerated and Table 6 summarises their efficacy profiles.^[21,44] The most effective triptan is subcutaneous sumatriptan 6 mg, which has the greatest 2-hour efficacy and fastest onset of action. Following this, the nasal spray triptans, sumatriptan 20 mg and zolmitriptan 5 mg, have faster onsets of action and possibly slightly greater efficacy than any of the oral formulations.^[44,45] The available data shows that there seem to be only minor differences in the clinical profile of the oral triptans,^[45,46] although individual patients may respond differently to individual triptans. The orally dispersible (ODT) formulations of zolmitriptan and rizatriptan may provide potential advantages over the usual conventional tablet formulations in terms of ease and convenience of use. However, it should be noted that these dispersible formulations are not absorbed in the mouth, but in the stomach, as with the conventional tablet formulations.

Subcutaneous sumatriptan is also effective when used as a rescue medication,^[15] and opiate analgesics may also be used, but under controlled conditions to prevent the development of overuse and consequent withdrawal symptoms.^[15]

Certain groups of patients should either not receive triptans, or be prescribed them with caution. Triptans are contraindicated for patients with evidence of existing cardiovascular disease, uncontrolled hypertension, severe renal and hepatic impairment, and for those receiving other triptans, ergotamine and its derivatives and monoamine oxidase inhibitors (MAOIs). Eletriptan is specifically contraindicated for patients concomitantly using selective serotonin reuptake inhibitors (SSRIs). Caution should be used when prescribing triptans to patients with risk factors for cardiovascular disease (e.g. history of smoking or men aged > 40 years), controlled hypertension, any renal or hepatic disease, hypersensitivity reactions and pregnant or breast-feeding women.^[47,48] Patients with the rare migraine variants should also not be prescribed triptans.

Drugs without good evidence of utility include paracetamol monotherapy (due to lack of efficacy), and opiates and barbiturates (due to safety concerns).^[15] Oral ergotamine has limited efficacy due to poor bioavailability, and is associated with a range of potentially severe side-effects (ergotism).^[49] Parenteral formulations of ergotamine and dihydroergotamine (DHE) are more effective,^[49] but are not currently available in the UK.

Recommendations. Based on this evidence, aspirin and NSAIDs, used in high doses, analgesic-antiemetic combination medications and isometheptene combination medications can be recommended as first-line acute treatments for mild-to-moderate migraine attacks. Triptans are the obvious choice for moderate-to-severe migraine attacks, and for patients who fail on previous therapies. Ergotamine and preparations containing opiate analgesics should be mostly avoided, except for use as rescue medications and where their use can be monitored.

Migraine Prophylaxis. The primary goals of prophylactic therapy have been identified as reducing headache frequency by > 50% and/or improving a concurrent condition.^[50] Although the 'ideal' prophylactic would abolish migraine attacks altogether, in clinical trials only a maximum of about one-half of patients respond to this extent.^[50] Patients therefore need to have an effective acute treatment available for the inevitable breakthrough attacks that occur.^[17,21]

Due to the risk of side-effects with these therapies, they also need to be well tolerated. The patient should also express a preference and/or satisfaction with these therapies.^[17]

Migraine prophylaxis is considered worth using if the patient:

• Suffers from frequent high-impact migraine attacks. (The definition of what constitutes 'frequent migraine' requiring prophylaxis varies in different countries, patients with three or more attacks per month in the USA^[17] or four or more attacks per month in the UK^[12] are usually given migraine prophylaxis.)

• Experiences significant disability, despite receiving acute treatment.

• Suffers from concomitant co-morbidities, or a medical illness that precludes effective acute therapy.

• Is at risk of over-using acute medications and therefore developing chronic daily headache.

• Has one of the rare migraine subtypes, such as hemiplegic or basilar migraine, migraine with prolonged aura or migrainous infarction, for which triptans cannot be used.^[17]

However, it can also be worth revisiting the diagnosis, as frequent migraine attacks may be an indication of chronic daily headache.^[6]

Prophylactic Therapies. Several different drugs are used in the UK as migraine prophylaxis, not all of them licensed for this use. The Duke database has captured evidence-based data on their clinical profiles, as summarised in Table 7.^[39]

Drugs with proven efficacy for migraine prophylaxis in well-controlled clinical trials and which are well-tolerated include the beta-blockers propranolol, timolol and metoprolol, the anticonvulsant sodium valproate and the antidepressant amitriptyline. The serotonin antagonists methysergide and pizotifen have some evidence of efficacy, but have side-effects that can limit their use, whilst the central alpha agonist clonidine has little objective evidence for its effectiveness.^[39]

Recommendations. Beta-blockers are the obvious first-line agents for migraine prophylaxis in UK general clinical practice. These drugs are often effective at low doses, but can be up-titrated if necessary. Sodium valproate and amitriptyline are also effective but, as they are not licensed as migraine therapies in the UK, may be best reserved for use by specialists. The serotonin antagonists are probably best reserved as second-line therapies if the above treatments fail.

Complementary Therapies. Many patients prefer to use complementary medications instead of, or together with, prescribed medications for their migraine. Reasons for this include an exhaustion of all conventional options, feeling this is a fashionable option, obtaining a perceived high level of care from a complementary therapist and greater perceptions of personal control and safety.^[22]

Some complementary medications have demonstrated efficacy for migraine in one or more controlled clinical trials, including feverfew, magnesium, vitamin B₂ and acupuncture prophylaxis.^[21] Therapies which are often used, but do not have convincing evidence of efficacy to date include low-dose aspirin, homeopathic medications, aromatherapy and food exclusions following allergy testing (Table 8).^[21]

Recommendations. Several complementary prophylactic therapies, such as feverfew, acupuncture, riboflavin and magnesium, all show some efficacy in migraine prevention, although their long-term side-effects are not properly understood. The physician can recommend use of these therapies, one at a time, if the patient shows interest and wants to try something new. However, effective acute medications should always be available, as these therapies are no more a 'cure' than any of the conventional prophylactic agents.

The patient needs to decide which, if any, of these therapies appeals to them, is affordable or practicable to their lifestyles. In addition, alternative stress reduction strategies, such as aromatherapy, reflexology or yoga, may all be beneficial. It needs to be stressed that patients should only consult with accredited complementary practitioners.

Follow-up Procedures

Migraine attacks typically occur for several decades of the sufferer's life,^[1] and long-term management of the condition should therefore be mandatory. After the first consultation, the patient should be asked to return to the surgery on a regular basis for review. The patient can be asked to complete questionnaires that can help in the monitoring of care:

• Headache diaries are invaluable to capture the patient's pattern of headaches over time, and several diaries are available.^[22]

• MIDAS and HIT questionnaires can capture the impact of migraine over time and may also be useful in assessing the response to therapy.^[35]

The efficacy of acute and prophylactic medications should be monitored at each clinic visit. For acute medication, patients who are treated effectively should continue with their existing therapy. Patients who fail on analgesics or analgesic-combination medications can be provided with migraine-specific medications, usually a triptan. Patients who fail on one triptan can be provided with an alternative triptan. Patients who find their oral triptan effective, but inconvenient to use, can be provided with an alternative formulation that may suit their needs better (e.g. ODT or nasal spray formulations). Patients refractory to triptans, or who require regular rescue therapy, may require opiate drugs for rescue. However, due to the dangers of habituation and chronic daily headache, it is probably best to refer these patients to a specialist for treatment.

Prophylaxis is not intended as a long-term management strategy, but should be reviewed from 4-6 weeks. If the treatment is effective, without causing chronic side-effects, treatment can be continued up to 6 months. If not, the dose can be increased (up to the maximum allowed) or an alternative prophylactic drug can be supplied. At 6 months, the prophylactic drug can be withdrawn if the frequency of attacks is reduced. Providing the frequency remains reduced after withdrawal, it may be appropriate to revert to acute treatments only.

Patients who are refractory to repeated acute and/or prophylactic medications may need to be referred to a specialist for further care.

http://www.medscape.com/viewarticle/446557_3