Migraine%20headache Treatment

Principles of Treatment - Acute Treatment

• Therapy should be guided according to frequency, duration and severity of attacks, associated symptoms, degree of disability, history of treatment, evidence-based efficacy and patient’s preference
• Coexisting medical conditions should also be considered in migraine therapy
  • Myocardial infarction, stroke, epilepsy, affective and anxiety disorders are common in patients with migraine
• Effective therapy should be established and promptly used to decrease pain and disability
• Non-oral route of administration should be used in patients who suffer migraines associated with severe nausea and vomiting
• Antiemetics should be used if nausea and vomiting are likely to occur
• Educate patient about avoiding medication overuse
  • Administer preventive therapy if necessary
• To avoid headache from drug overuse, simple analgesics should be taken for a maximum duration of 15 days per month while combined analgesics should be taken for a maximum duration of 10 days per month

Goals of Treatment - Acute Treatment

• Abort migraine attack
• Treat migraine attack rapidly and consistently without recurrence
• Restore patient’s ability to function
• Minimize need for back-up and rescue medications
• Self-care should be optimized
• Avoid adverse effects

Criteria for a Successful Treatment

• Pain-free after 2 hours
• Improvement of migraine from moderate or severe to mild or none after 2 hours
• Consistent efficacy in 2 of 3 migraine attacks
• Sustained pain relief defined as absence of headache recurrence and no further intake of drugs within 24 hours

Management Strategy - Acute Treatment
Stratified Care Strategy

• Acute treatment is based on headache severity
• Promotes the use of migraine-specific agents for moderate to severe headache regardless of the previous response to other agents

Stepped Approach

• Use of drugs is based on a progressive predetermined way
• Safe, effective and inexpensive medications are used as first-line agents
• If initial agent fails, migraine-specific medication is then used
• Eg commence treatment with an analgesic with or without antiemetic, then escalating to triptan or 5HT1 receptor agonist

Principles of Therapy - Prophylactic Treatment 

• Agent used should be started at a low dose and slowly titrated to higher doses
  • Increase dose until benefit is seen or until limited by adverse events
• Choice of drug agent depends on the following: Adverse effects, presence of comorbidities, drug interactions, evidence-based efficacy, patient preference
• Migraine prophylaxis is considered successful if there is at least 50% decrease in the frequency of migraine attacks per month within 3 months
• Adequate treatment trial period of at least 8 weeks at the effective dose or target therapeutic dose of the drug should be observed to optimize the possibility of therapeutic response before switching to other prophylactic treatment if there is no response
  • Benefits of CGRP antagonists should be assessed after 3 months of treatment for those with monthly administration and after 6 months after start of treatment in those with quarterly treatment
• Prophylactic drugs that are effective should be continued for 4-6 months followed by withdrawal by tapering the dose over 2-3 weeks
• Avoid overuse of drugs for acute treatment (eg analgesics, ergots, triptans)

Goals of Treatment - Prophylactic Treatment 

• Reduce severity, duration and frequency of migraine headache
• Improve function, patient’s quality of life and decrease disability
• Improve response and avoid advancing to acute therapy 
• Reduce cost
• Allow patients to have a sense of control of their own disease
• Prevent progression to chronic migraine and occurrence of medication overuse headache
• Reduce the risk of neurologic damage in patients with hemiplegic migraine, migraine with brainstem aura, persistent aura without infarction or migranous infarction

PHARMACOLOGICAL THERAPY - ACUTE TREATMENT

Nonsteroidal Anti-inflammatory Drugs (NSAIDs) including Analgesics

• Analgesics are the first-line agents for moderate migraine attacks
• Efficacy and tolerability of nonsteroidal anti-inflammatory drugs have been shown in a number of clinical trials
• Paracetamol is recommended as acute treatment for moderate migraine
  • May be considered for patients with acute migraine headache with contraindications to other therapies or during pregnancy
• Aspirin is recommended for acute treatment in patients with all severities of migraine
• Intravenous Aspirin with or without Metoclopramide is the first choice in patients with severe migraine in an emergency situation
• For resistant attacks, nonsteroidal anti-inflammatory drugs (oral, rectal or IM) can be given following, or added to, a triptan
• The use of selective COX-2 inhibitors in acute migraine treatment has been investigated in clinical trials

Triptans (Serotonin 5HT1 Receptor Agonists)

• Efficacy of triptans ranges in comparative efficacy as shown in clinical trials; however, there are unpredictable individual variations in response to different triptans
• They have better efficacy when given at the very onset of the headache or while the migraine pain is at mild level
  • Not safe and effective when administered during the aura
• Oral triptans are recommended for acute treatment of migraine with all severities if previous attacks are not controlled by simple analgesics
• Use is limited to maximum of 9 days/month
• Sumatriptan is available in nasal, subcutaneous (SC) and rectal formulations
  • Subcutaneous Sumatriptan has the fastest onset of efficacy, yet also has the highest recurrence rate; may also be considered in treatment of severe migraine
  • Nasal formulation is not recommended if vomiting precludes oral therapy since its bioavailability depends largely on ingestion
  • Suppositories should be given in patients with vomiting
• Use of Zolmitriptan nasal formulation is considered in patients with severe migraine; may also be used even if vomiting is already occurring since up to 30% is absorbed through the mucosa
• It is confirmed on several trials that patients who fail to obtain adequate relief with 1 triptan can benefit from another in subsequent attacks
  • Each triptan should be tried in 3 attacks before it is rejected
  • Change in dosage and route of administration should be considered

Ergot Alkaloids

• Used in patients with very long migraine attacks or with regular recurrence due to its lower recurrence rate
• Use has been limited by their high potential to cause medication overuse headache and rebound headache
  • Intake should be limited to 10 days/month

Ergotamine

• Combinations with Caffeine, Butalbital and/or Belladonna are available
• Historically has been used to treat moderate-severe migraine headache
• Restricted in patients with very long migraine attacks or with regular recurrence due to its longer half-life and lower recurrence rate
  • Use has been limited by high potential to cause medication overuse headache and rebound headache
  • Suppository formulation is available
  • Should not be taken concomitantly with any triptan

Dihydroergotamine (DHE)

• Available in rectal, parenteral and nasal formulations
  • Nasal formulation is effective and safe as monotherapy
• More appropriately used in severe migraines
• Recommended as treatment for status migrainosus

5-HT_1F Receptor Agonist

• Eg Lasmiditan
• Currently approved for the acute treatment of migraine, with or without aura, in adults
• Two randomized, double-blind, placebo-controlled trials demonstrated effectiveness of Lasmiditan for the acute treatment of migraine

Antiemetics

• Antiemetics have been used in conjunction with migraine medications to control nausea and vomiting
• Fair evidence has shown that Metoclopramide may be effective as monotherapy for acute attacks
  • It has mild analgesic efficacy in migraine when given orally and higher efficacy when given IV
• Domperidone is less sedating than Metoclopramide; has also less risk of extrapyramidal effects
• Available in different forms (eg oral, parenteral, rectal)

Other Drugs

• Opioid Analgesics
  • Opiates and tranquilizers are not recommended in the treatment of acute migraine
  • There are no studies that support the effectiveness of opiates
• Calcitonin Gene-Related Peptide (CGRP) Antagonists
  • Eg Rimegepant, Ubrogepant, Zavegepant
  • Approved by the US FDA for acute treatment for patients unresponsive or intolerant to at least 2 triptans
  • Rimegepant and Ubrogepant are oral agents approved for the acute treatment of migraine with or without aura
  • Zavegepant is available as a nasal spray and is approved for the acute treatment of migraine with or without aura in adults
  • Ubrogepant and Zavegepant are not recommended for the preventive treatment of migraine

Combination Therapy

• There is some evidence that combination of Sumatriptan and Naproxen is superior to either drug alone
  • Combination reduces the development of headache recurrence and may be considered for the treatment of patients with acute migraine
• Fixed combinations containing Paracetamol, Aspirin and caffeine have been shown to be effective
  • They are better than single substances or combinations without caffeine
• Caffeine should be added as first choice in treating intermittent, infrequent headache
• Other combinations:
  • Oral analgesic or nonsteroidal anti-inflammatory drug with or without antiemetic plus specific anti-migraine drugs, followed by
  • Rectal analgesic with or without antiemetic plus specific anti-migraine drugs

Menstrual Migraine

• Acute treatment is same as that of non-menstrual headache
  • May be necessary to repeat the treatment since menstrual attacks may have longer duration

Migraine in Pregnancy

• Paracetamol may be used if migraine occurs anytime during pregnancy
• In the 2nd trimester of pregnancy, nonsteroidal anti-inflammatory drug can be given
• Non-pharmacological management is preferred
  • Biofeedback, relaxation, transcutaneous supraorbital nerve stimulation and physical therapy may be tried
• Ergotamine and dihydroergotamine are contraindicated during pregnancy

PHARMACOLOGICAL THERAPY - PROPHYLAXIS

Antiepileptic Drugs

• Valproic acid, Divalproex sodium and Topiramate have been shown to be effective in preventing migraines
  • Efficacy is comparable with Metoprolol, Propranolol and Flunarizine
  • Topiramate has been considered as one of the drugs of first choice for migraine prophylaxis
  • Recommended as first-line prophylactic agents for chronic migraine

Antidepressants

• Useful in patients with coexisting depression or insomnia
• Not all antidepressants are effective
• Amitriptyline has been studied more than any other antidepressant
  • Has been shown statistically to be effective in preventing migraines
  • Recommended as first-line agent for chronic migraine prophylaxis
• Fluoxetine has been studied with inconclusive evidence of efficacy
• Venlafaxine may also be recommended for migraine prophylaxis
• Other tricyclic antidepressants ie Nortriptyline and Protriptyline are considered second-line agents for chronic migraine prophylaxis in patients refractory to the first-line agents

Beta-Blockers

• Useful in patients with coexisting essential tremors, anxiety and/or panic attacks
• Not recommended for migraine prevention in patients >60 years and in smokers
• Propranolol, Metoprolol and Timolol have both been shown to be consistently effective in preventing migraines
  • Propranolol is recommended as first-line agent for chronic migraine prophylaxis
• Atenolol, Bisoprolol and Nadolol have shown limited effectiveness

Botulinum toxin A

• Currently approved for prophylaxis of chronic migraine headaches
• Given approximately every 12 weeks as multiple injections around the head and neck

Calcium Channel Blockers

• Eg Flunarizine, Verapamil 
• Flunarizine has shown efficacy in migraine prophylaxis in several studies
• Flunarizine has been recommended as one of the drugs of first choice for prophylaxis
  • Treatment option for women of childbearing age
• Verapamil may be an alternative for chronic migraine prophylaxis in patients refractory to the first-line agents

Calcitonin Gene-Related Peptide (CGRP) Antagonists

• Act by binding to and subsequently inhibiting CGRP receptor or ligand
• Eptinezumab, Erenumab, Fremanezumab, Galcanezumab
  • Human monoclonal antibodies acting as CGRP antagonists
  • Currently approved subcutaneous injectables for episodic and chronic migraine prophylaxis who have at least 4 migraine days per month
• Atogepant, Rimegepant
  • Oral CGRP antagonist approved for the preventive treatment of episodic migraine
• Effective for patients who failed prior prophylactic therapy and in patients on concurrent oral prophylactic therapy
• Have been shown to reduce the number of migraine or headache days and number of days using acute medications, and improve disability
• No need for gradual dose titration unlike oral prophylaxis
• Indicated when patient is ≥18 years and
  • Diagnosed with migraine with or without aura and intolerant or unresponsive to a 6-week trial of at least 2 of the following: Beta-blocker (Atenolol, Metoprolol, Nadolol, Propranolol, Timolol), Divalproex sodium/valproate sodium, serotonin-norepinephrine reuptake inhibitor (Duloxetine, Venlafaxine), tricyclic antidepressant (Amitriptyline, Nortriptyline), or Topiramate and with at least moderate disability or
  • Diagnosed with chronic migraine and intolerant or unresponsive to a 6-week trial of at least 2 of the following: Beta-blocker (Atenolol, Metoprolol, Nadolol, Propranolol, Timolol) Divalproex sodium/valproate sodium, serotonin-norepinephrine reuptake inhibitor (Duloxetine, Venlafaxine), tricyclic antidepressant (Amitriptyline, Nortriptyline), or Topiramate or intolerant or unresponsive to a minimum of 2 quarterly injection of OnabotulinumtoxinA

   

Other Drugs

Angiotensin Receptor Blockers

• Candesartan has shown limited effectiveness in preventing migraines
  • Can be considered as an alternative for chronic migraine prophylaxis in patients refractory to first-line agents

Nonsteroidal Anti-inflammatory Drugs

• May be considered in patients in need of migraine prophylaxis
• Should be used with caution as prolonged use (≥15 days/month) may cause medication overuse headache

Serotonergic Antagonists

• Use of Methysergide is limited to short-term prophylaxis (maximum of 6 months) because of adverse effects;also associated with severe rebound headache
• Pizotifen is not recommended because of its poor efficacy and severe side effects

• Eg Frovatriptan, Naratriptan, Zolmitriptan
• Frovatriptan should be considered as a prophylactic treatment in women with perimenstrual migraine 2 days prior up to 3 days after bleeding starts

Herbal/Vitamin/Mineral

• Although the level of evidence is low, the following have been recommended for migraine prophylaxis due to fewer side effects and modest efficacy:
  • Co-enzyme Q10
    • One randomized placebo-controlled trial has shown that co-enzyme Q10 has decreased migraine attack frequency and with good tolerability
  • Magnesium
  • Riboflavin

Hormone-Related Migraine

• Prophylaxis should be tried for a minimum of 3 cycles at maximum dose before it is deemed ineffective
• Triptans (eg Frovatriptan, Naratriptan, Zolmitriptan) have been studied in clinical trials of short-term prophylaxis of menstrual migraine
• There are limited studies available on the use of ergot alkaloids as cyclic prophylaxis
• Hormones are considered supplements in patients with menstrual migraine
  • In a patient with intact uterus and menstruating regularly, progestogens are not necessary
  • Patients suffering from menstrual migraine can benefit from the following drugs: Combined hormonal contraceptives (CHC), progestogen-only oral Desogestrel, subdermally-implanted Etonogestrel and injectable depot Progestogen
  • The following are contraindications to contraceptive use of combined hormonal contraceptives: Migraine with aura and migraine treated with ergot derivatives

Migraine in Pregnancy

• Most women with migraine improve during pregnancy, hence prophylaxis is not usually needed
• If prophylaxis is necessary, Magnesium and Metoprolol are recommended
  • Propranolol has the best safety profile
  • Amitriptyline in the lowest effective dose can also be us

Behavioral and Physical Methods For Migraine Prophylaxis

• Appropriate for patients who:
  • Prefer non-pharmacological methods
  • Do not respond to prophylactic medication
  • Cannot tolerate or in whom pharmacologic agents are contraindicated
  • With history of medication overuse
  • Pregnant, lactating or women planning to get pregnant
  • Have significant stress or deficient stress-coping skills
• May combine behavioral or physical treatments with pharmacotherapy if necessary
  • Have been shown to provide more benefits than either modality alone

Goals of Therapy

• Reduce frequency and intensity of headache
• Reduce reliance on pharmacotherapy
• Reduce disability caused by headache
• Increase personal control over headache
• Decrease headache-related distress and psychological symptoms

Relaxation Training, Stress Reduction and Coping Strategies

• Considered 1st-line treatments where a specific indication exists (eg stress, anxiety)
• Yoga and meditation are said to enhance stress management
• Train patients to control muscle tension, use mental relaxation and/or visual imagery
• Has been found to be somewhat effective in preventing migraines

Biofeedback Therapy

• Standard thermal and electromyographic (EMG) biofeedback training are usually the techniques of choice
• Thermal biofeedback combined with relaxation training may be somewhat effective
• Should be conducted by a trained healthcare provider
• It is time-consuming and requires patient commitment

Cognitive-Behavioral Therapy (CBT)

• Psychotherapeutic intervention
• The goal is to teach skills to identify and control stress, and minimize its effects
• Hypnotherapy has also been used
• Cognitive-behavioral therapy may be considered somewhat effective

Physical Therapy

• May be useful where a specific condition exists (eg migraine due to neck dysfunction)
• Improving physical fitness may decrease susceptibility to migraine
• May be beneficial in the therapy of chronic migraine in patients with constant muscle tension

Acupuncture

• Fine needles pierce skin at specific “pressure points” to relieve pain
• It is believed that endorphins are released into patient’s system which relieve pain
• Controlled studies have produced mixed findings for the effectiveness of acupuncture

Neuromodulation

• Involves stimulating the nervous system centrally or peripherally with the use of an electric current or a magnetic field
• Option for patients with poor response, intolerance or contraindications to drug treatments or who prefer non-pharmacologic treatments
• Singe-pulse transcranial magnetic stimulation and electrical trigeminal nerve/supraorbital nerve stimulation is recommended for acute and preventive treatment of migraine
  • Transcranial magnetic stimulation may be used as a second-line modality for patients with episodic migraine with aura and unresponsive or intolerant to first-line therapy with triptans or other drugs
  • Transcutaneous supraorbital nerve stimulation was found to be beneficial for patients with episodic migraine
• Noninvasive vagus nerve stimulation is recommended for the acute treatment of migraine