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Treatment

 

Migraine is not always managed effectively by physicians and continues to be under-diagnosed and under-treated in clinical practice, about half of migraine patients stop seeking care for their headaches, partly because they are dissatisfied with therapy. Indeed, public surveys indicate that headache sufferers are among the most dissatisfied patients. (12)

Migraine is heterogeneous (among sufferers and between attacks) in frequency, duration, and disability. Some migraineurs have fewer than one attack a month while others have one or more attacks a week. (17)Some are quite disabled by their headaches, while others are not. Therefore, it is appropriate to stratify the care of the migraine population by headache frequency, severity, and level of disability, and to consider prevention for those patients whose migraine has a substantial impact on their lives. (92)

General principles of management (93)

        Establish a diagnosis.

        Educate migraine sufferers about their condition and its treatment. Discuss the rationale for a particular treatment, how to use it, and what adverse events are likely.

        Establish realistic patient expectations by setting appropriate goals and discussing the expected benefits of therapy and how long it will take to achieve them. Empower the patients to be actively involved in their own management by encouraging patients to track their own progress through the use of diary cards, flow charts, headache calendars, and forms for tracking days of disability or missed work, school, or family activities. Treatment choice depends on the frequency and severity of attacks, the presence and degree of temporary disability, and associated symptoms such as nausea and vomiting.

        Create a formal management plan and individualize management: consider the patientís response to, and tolerance for, specific medications. Consider comorbidity/coexisting conditions. Coexisting conditions (such as heart disease, pregnancy, and uncontrolled hypertension) need to be ascertained as they may limit treatment choices.

        Encourage the patient to identify and avoid triggers.

Treatment of acute attacks of migraine

 

The goals of migraine management are to treat attacks rapidly and consistently, restore the patientís ability to function, minimize the use of back-up and rescue medications, optimize self-care and reduce subsequent use of resources, be cost effective for overall management, and have minimal or no adverse events.(93)

 

Non specific Medications :analgesics and NSAIDs

 

Aspirin, ibuprofen, tolfenamic acid, naproxen sodium, aspirin, and caffeinecombination, and acetaminophen and butalbital-containing(95) agents are effective in acute migraine treatment.(94)

 

Specific Medications

 

Ergotamine, DHE, and the triptans are potent agonists for the 5-HT1B/1D and in some cases the 5-HT1F receptors. The ergots have much greater receptor affinity at 5-HT1A, 5-HT2, adrenergic, and dopaminergic receptors than the triptans, leading to more adverse effects. All are indicated for acute migraine treatment. Patients with sepsis, renal or hepatic failure, and cerebral or peripheral vascular disease should avoid ergotamine and DHE. There is remarkably little consensus among physicians as to how many risk factors preclude the use of triptans and what constitutes an appropriate evaluation.(97,98)

 

 

 

Selective 5-HT1 Agonists (Triptans)

 

The first triptan was sumatriptan, followed by zolmitriptan, naratriptan, rizatriptan, almotriptan, frovatriptan, and eletriptan. All are more centrally penetrant than sumatriptan. Eletriptanís central penetrance is usually limited, since it is a substrate for the p-glycoprotein (PGP) pump. Drugs that inhibit the PGP pump would allow higher central penetrance. All the triptans are effective.Patients whose migraine attacks are associated with moderate to significant disability or who fail to respond to other medications are candidates for treatment with a triptan.Triptans relieve head pain and nausea and vomiting. They are effective even if given after the onset of migraine, but are more effective when the pain is mild.

Seven triptans (sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, frovatriptan, and eletriptan) are currently available. They are safe, effective, and appropriate first-line therapy for the patient who has a moderate to severe migraine headache or for whom analgesics have failed to provide adequate relief.(96)

What form of triptan should be used?

Headache severity, rapidity of onset, and duration are important factors when making treatment decisions. When the headache intensifies rapidly (<30 minutes), or nausea and emesis are early and severe associated symptoms, a non-oral route of administration is appropriate. Subcutaneous sumatriptan is the fastest and most effective triptan. The nasal spray formulation of sumatriptan or zolmitriptan may provide a faster onset of action than the oral triptans, but sumatriptan nasal spray is often associated with a disagreeable taste. The oral formulations can be divided into two classes. Sumatriptan, rizatriptan, zolmitriptan, almotriptan, and eletriptan have the highest 2-hour efficacy, can provide headache relief within 30 to 60 minutes (96, 97, 78)

 

Ergotamine and Dihydroergotamine

 

Ergotamine is used to treat moderate to severe migraine if cost is a factor.Some patients still respond preferentially to rectal ergotamine. DHE has fewer Adverse effects than ergotamine and can be administered intramuscularly, subcutaneously, or intravenously. The best efficacy evidence exists for DHE nasal spray. DHE is associated with a low headache recurrence rate (<20%), has fewer Adverse effects, and is less likely than ergotamine to produce rebound headache. Repetitive intravenous DHE has become the mainstay of acute symptomatic treatment for intractable headache (94, 99,113).

 

 

Preventive treatment

 

Prophylactic treatment should be considered only: (102)

 

1)     When attacks of migraine occur more than two or three times a month.

2)     When the attacks are severe and limit normal activity.

3)     When the patient is unable to cope with the attacks.

4)     When symptomatic therapies have failed or have had serious side effects.

5)     When attempts at non-pharmacological prevention have failed.

 

 

Beta-Blockers

Propranolol, nadolol, atenolol, metoprolol, and timolol are effective. Partial

Agonists and those with intrinsic sympathomimetic activity are not effective.

Their relative efficacy has not been established; choice is based on beta-selectivity, convenience of drug formulation, Adverse effects, and the patient's individual reaction. (21)

Beta-blockers can produce behavioral adverse effects, such as drowsiness, fatigue, lethargy, sleep disorders, nightmares, depression, memory disturbance, and hallucinations; they should be avoided when patients have depression or low energy. Decreased exercise tolerance limits their use by athletes. Less common adverse effects include impotence, orthostatic hypotension, bradycardia. Beta-blockers are useful for patients with angina or hypertension. They are relatively contraindicated for patients with congestive heart failure, asthma, Raynaud's disease, and insulin-dependent diabetes. (101,78)

 

 

Antidepressants

 

Antidepressants consist of a number of different classes of drugs with different mechanisms of action:

A)    MAOIs.

B)    monoamine reuptake inhibitors.

(1)               nonselective tricyclic antidepressants (TCAs).

(2)               selective serotonin reuptake inhibitors (SSRIs).

(3)               selective serotonin and norepinephrine reuptake inhibitors (SNRIs).

C)    monoamine receptor targeted drugs:

(1) serotonin (2) norepinephrine; and (3) dopamine.

Amitriptyline is the only antidepressant with fairly consistent support for efficacy. Adverse effects from TCAs are common: antimuscarinic effects include dry mouth and sedation. They cause increased appetite and weight gain; cardiac toxicity and orthostatic hypotension occur occasionally.[129] There is one positive trial for fluoxetine. Sexual dysfunction is common with SSRIs. Antidepressants are especially useful for patients with comorbid depression and anxiety disorders.(102,78)

 

Calcium-Channel Blockers

 

The US Headache Consortium(102) analyzed 45 controlled trials of calcium channel blockers. Flunarizine was effective, nimodipine had mixed results, and nifedipine was difficult to interpret. Verapamil was more effective than placebo in two of three trials, but both positive trials had high dropout rates, rendering the findings uncertain. Constipation is the most common adverse effects of verapamil. Flunarizine is the most effective drug of this class, Adverse effects include Parkinsonism, depression and weight gain.

 

 

 

 

Anticonvulsant Medications

 

There is a strong, consistent(102) support for the efficacy of divalproex sodium and sodium valproate. . The most frequently reported. Adverse effects include nausea, infection , alopecia , tremor , asthenia, dyspepsia , and somnolence . Weight gain was reported in some patients. Hepatotoxicity is the most serious side effect, but irreversible hepatic dysfunction is extremely rare in adults. (103)

Gabapentin (1800 to 2400 mg), in a randomized, placebo-controlled, double-blind trial, was superior to placebo in reducing migraine attack frequency by 50% in about one-third of patients. The most common. Adverse effects were dizziness or giddiness and drowsiness. Relatively high patient withdrawal rates due to Adverse effects were reported in some trials.(104)

Topiramate, a derivative of the monosaccharide D-fructose, was effective in reducing migraine attack frequency by 50% in half of the patients.(93)

Divalproex and topiramate are useful in patients with epilepsy, anxiety disorder,

or manic-depressive illness. They can be used in patients with depression, Raynaud's disease, asthma, and diabetes, circumventing the contraindications to beta-blockers(78).

 

Serotonin Antagonists

 

Methysergide is an effective drug for migraine prevention. Adverse effects include transient muscle aching, claudication, abdominal distress, nausea, weight gain, and hallucinations. The major complication is rare (1/2500) retroperitoneal, pulmonary, or endocardial fibrosis. To prevent this complication, a four week medication-free interval is recommended after six-months of continuous treatment(105). Pizotifen thougheffective however Adverse effects are multiple they include drowsiness, increased appetite, and weight gain (94).

 

 

 

Natural products

 

Feverfew(107) (Tanacetum parthenium) is a medicinal herb whose effectiveness has not been totally established. Riboflavin (400mg) was also effective in migraine prophylaxis.

 

Newer treatments

 

Botulinum toxin type A (Botox 25, or 75U) was effective in one placebo-controlled, double-blind trial. It was injected into glabellar, frontalis, and temporalis muscles. The 25U treatment group was significantly better than the placebo group in reduction of mean frequency of moderate to severe migraines during days 31 to 60, incidence of 50% reduction in all migraine at days 61 to 90, and reduction in all migraine at days 61 to 90. (108)