1. Sufferers rarely go without acute treatment of some kind for individual attacks. Use of acute treatment should generally be limited to no more than 2 to 3 d/wk to avoid medication-overexposure headache.

2. The goal of abortive or acute therapy is to provide rapid, well-tolerated relief of headache and associated symptoms with minimal impairment of functional ability.

3. The choice of acute treatment depends on headache characteristics and patient preference.

4. The triptans (serotonin agonists with activity at 1B and 1D receptors) are first-line medications for the abortive therapy of migraine headache; seven available triptans are listed, but not all are available in every country.

5. All triptans are available in oral formulations; rizatriptan and zolmitriptan are also available as orally disintegrating tablets that dissolve in the mouth but are absorbed intestinally. A fixed-dose combination of sumatriptan and naproxen is available. Sumatriptan and zolmitriptan are available as nasal sprays. Sumatriptan is the only triptan available as a subcutaneous injection. Sumatriptan is also available in a breath-activated delivery system. Sumatriptan is available without a physician prescription in some countries, although interaction with a pharmacist is usually required.

6. The oral and orally disintegrating tablets are best administered at mild or mild-to-moderate headache intensity to ensure their absorption. They should be administered in their optimum doses and may be repeated after 2 hours (for naratriptan, every 4 hours).

7. Table 4-1 lists the tablet sizes and optimum, maximum single, and maximum daily doses of the oral triptans.

8. Almotriptan, eletriptan, rizatriptan, sumatriptan, and zolmitriptan, in their optimum doses, have similar 2-hour efficacy rates. They also have similar recurrence rates of approximately one-third.

9. Frovatriptan and naratriptan have 2-hour efficacy rates approximately half those of the other triptans. However, their duration of action is prolonged because of their longer plasma-elimination half-lives.

10. Triptans are generally well tolerated. The most common side effects of oral triptans are dizziness, paresthesias, and flushing. Neck or chest tightness can occur; the latter is generally not thought to be caused by myocardial ischemia, with multiple hypothesized causes including esophageal spasm. These “triptan sensations” are usually mild and transient. If a particular triptan is neither effective nor tolerated, another should be tried.

11. Triptans are selective for the cranial circulation, but a small degree of coronary artery constriction can occur. Therefore, they are contraindicated in patients
with known cerebrovascular or coronary artery disease or those at high risk for coronary artery disease. Uncontrolled hypertension is a contraindication to use. Rizatriptan, sumatriptan, and zolmitriptan are also contraindicated with the concomitant use of a monoamine oxidase inhibitor. The concomitant use of propranolol requires a 50% reduction in rizatriptan dose because of interference with the breakdown of this triptan. Eletriptan should not be used within 72 hours of taking medications that are inhibitors of CYP3A4 enzyme (mycin antibiotics, antifungal and antiviral medications).

12. The U.S. Food and Drug Administration has issued a safety alert about the risk of serotonin syndrome when triptans are used with selective serotonin or serotonin/norepinephrine reuptake inhibitors. It recommends weighing the potential risk of the syndrome with the expected benefit of using the combination, discussing this with patients, and following them closely during such treatment. There is little experimental support for this purported interaction.

13. When oral medications do not reliably relieve headache within a reasonable time, nonoral routes of administration should be considered.

14. Parenteral, nasal, or rectal routes can be used to administer migraine medications.

15. Dihydroergotamine and ergotamine are nonselective serotonin agonists with activity at a variety of other receptors including adrenergic and dopaminergic receptors. This accounts for their tendency to produce or aggravate nausea and
the possibility of more pronounced or prolonged vasoconstrictive effects. Thus, they are also contraindicated in patients with coronary artery disease or risk factors for coronary artery disease and should not be used concurrently with the triptan medications.

16. The sumatriptan and zolmitriptan nasal sprays can, if necessary, be repeated after 2 hours, with a maximum of 40 and 10 mg in 24 hours, respectively. In adults, sumatriptan nasal spray is used in a dose of 20 mg and zolmitriptan nasal spray in a dose of 5 mg. Dihydroergotamine nasal spray is given only once in 24 hours, in a dose of 0.5 mg per nostril followed by another 0.5 mg per nostril after 15 minutes. Side effects of the nasal sprays are nasal congestion, nasal irritation, and a bad taste in the mouth.

17. The indomethacin rectal suppository is given in a dose of 50 or 100 mg, if necessary, repeated after 0.5 to 1 hour, with a maximum of 200 mg in 24 hours. Its most common side effect is orthostatic light-headedness because of a systemic vasodilator effect. The medication is contraindicated in peptic ulcer disease and bleeding disorders.

18. The ergotamine-caffeine suppository contains 2 mg ergotamine in combination with 100 mg caffeine to improve its absorption. Nausea and vomiting are its most common side effects, and therefore, it is important to administer the medication with care. Patients are advised to take only one-fourth or one-third of a suppository at a time and repeat it, if necessary, every 30 minutes to 1 hour, with a maximum of two suppositories a day.

19. Injection is another route through which a medication can be administered for the abortive therapy of migraine headache. Following are the two medications that are available for parenteral administration:

20. The usual dose of dihydroergotamine is 1 mg given subcutaneously, intravenously (IV), or intramuscularly (IM). If given IV, the drug should be mixed with 5% dextrose in water (D5W) and not saline. Patients should be pretreated with an antiemetic drug to prevent worsening or precipitation of nausea or vomiting. Metoclopramide 10 mg, given IM or IV, is commonly used as pretreatment.

21. Sumatriptan is available for patient self-administration with an autoinjector. The injection is given subcutaneous in a dose of 6 or 4 mg, which can be repeated, if necessary, after 1 hour. Parenteral use of sumatriptan during aura does not prolong or worsen aura symptoms but has no effect on the subsequent headache. Thus, patients with aura may wish to delay its use until just before or after the headache begins. The most common side effects of the sumatriptan injection are a hot, tight, or tingling sensation, generally in the upper chest, anterior neck, and face, and light-headedness.

22. When abortive therapy is contraindicated, poorly tolerated, or ineffective, or when headaches occur more frequently than once a week, preventive therapy should be considered.

23. In 2019, a “ditan” (Lasmiditan) was approved by the FDA for acute treatment of migraine. Lasmiditan is a 5-HT1F receptor agonist without associated vasoconstriction. Lasmiditan is available as a 50- or 100-mg tablet to be taken at onset of migraine with option to repeat the dose in 2 hours. It is associated with significant risk of dizziness; patients should be advised to avoid driving and operating machinery for 8 hours after a dose.

24. An additional class of treatments are the “gepants” which have FDA approvals for acute and/or preventive treatment since 2019. The gepants are CGRP receptor antagonists with standard doses listed as follows:

25. Preventive therapy does not have to mean drugs. There is some evidence of benefit from nonpharmacologic treatments such as biofeedback-assisted relaxation or lifestyle alterations.

26. The quality and quantity of evidence supporting the use of preventive medications varies considerably. Medications, herbal preparations, or vitamins that show benefit in at least one reasonably large, well-conducted, double-blind, randomized controlled trial include the following:

27. β-Blockers with intrinsic sympathomimetic activity, pindolol, penbutolol, and acebutolol, are not effective in migraine. The mechanism of action of β-blockers in migraine is unknown but probably is not caused by blood pressure reduction.

28. Tricyclics such as amitriptyline and pizotifen may work by acting on the serotonergic system. The neurotransmitter serotonin inhibits the transmission of pain signals.

29. The calcium-entry blockers are a disparate group of drugs; not all show benefit in migraine. Those that do might work through effects on calcium-dependent processes involved in migraine, including synaptic transmission and neuronal membrane stability.

30. Divalproex sodium and topiramate are thought to be effective in part because they potentiate the inhibitory effects of γ-aminobutyric acid-ergic (GABA-ergic).

31. The choice of preventive medication depends on the features of the headaches and also on the risks, side effects, and possible benefits considering coexisting conditions.

32. When one preventive medication fails to provide relief or cannot be tolerated, another should certainly be tried. Clinical experience suggests that starting doses should be low and the dose gradually increased.

33. Headache activity normally waxes and wanes, so a treatment period of 2 to 3 months is necessary to be certain of a drug’s effect. This is best judged through the use of a headache diary or other objective measurements of headache activity.

34. Although single-drug therapy is preferred, some patients with resistant headache syndromes may benefit from combinations of two or even three preventive drugs.

35. β-Blockers are contraindicated in sinus bradycardia, atrioventricular block, obstructive pulmonary disease (asthma), and diabetes mellitus.

36. Apart from sedation, amitriptyline can cause dry mouth, constipation, and weight gain; pizotifen can cause weight gain, and flunarizine occasionally causes depression. Amitriptyline is contraindicated in glaucoma, prostate hypertrophy, epilepsy, and cardiac disease; flunarizine and pizotifen do not have contraindications.

37. Verapamil in its sustained-release form can be given twice daily; its most common side effects are constipation and hypotension. Verapamil is contraindicated in atrioventricular block and sick sinus syndrome because it slows down atrioventricular conduction.

38. The anticonvulsants divalproex sodium and topiramate are often not well tolerated. Divalproex sodium can cause nausea, tremor, weight gain, and hair loss, and topiramate can cause sedation, cognitive dysfunction, paresthesias, weight loss, and kidney stones. Divalproex sodium is contraindicated in liver disease or when liver function is abnormal. Exposure during the first trimester of pregnancy can cause neural tube defects. It should thus be used with caution or avoided in women of childbearing age.

39. In the absence of clinical trial evidence guiding the length of treatment, most experts continue the medications for 4 to 6 months and then taper them slowly. They can be resumed if headaches recur. The medications should be prescribed for at least 6 months, after which the dose is gradually decreased and the medication, if possible, discontinued.

40. Injectable monoclonal antibodies to CGRP or its receptor have become available since 2018. Erenumab, fremanzumab, and galcanezumab are CGRP ligand inhibitors and can all be dosed monthly with subcutaneous injections; patients on fremanzumab have the option to dose quarterly. Eptinezumab is an IV infusion that is dosed every 3 months.

41. The use of monoclonal antibodies for the treatment of migraine has been revolutionary. This form administration results in reduced drug-drug interactions with other common medications such as antibiotics, antidepressants, anti-seizure medications, and anticoagulants. In addition, this route of administration also results in less pill burden and improved medication adherence by avoiding daily dosing.

42. The monoclonal antibodies are generally associated with a favorable side effect profile. Erenumab was associated with constipation and has a warning for elevation in blood pressure, appropriate counseling and monitoring is recommended.

43. Patients with may become pregnant should not be on the monoclonal antibodies and counseling is necessary before initiation. Patients should cease use 5 months before planned pregnancy to allow for five half-lives to elapse for adequate clearance.

44. Please see #24 hereinbefore for additional information on the gepants for preventive treatment.

45. Botulinum toxin injection was approved by the FDA in 2010 for the preventive treatment of chronic migraine. Treatment involves standardized injection sites on face, head, and neck muscles following the PREEMPT protocol amount to 155 to 200 u every 12 weeks.

46. Relative disadvantages of the monoclonal antibodies, the gepants and botulinum toxin include higher costs, additional prior authorizations required for coverage and potentially insurance formulary coverage changes.

47. Devices are becoming more widely used in migraine management. Current FDA-approved devices include a transcutaneous supraorbital nerve stimulator (Cefaly) and a transcranial magnetic stimulator (Spring TMS) and a noninvasive vagal nerve stimulator (gammaCore)

1. Migraine with aura is treated as migraine in general, except that in its preventive therapy, β-blockers are often avoided because of theoretical worry that they may aggravate the neurologic symptoms.

2. There is no well-validated, practical acute treatment for aura symptoms. Experimentally, ketamine seems to abort aura in about half the cases. Anecdotal accounts suggest benefit from magnesium, furosemide, Compazine suppositories, or rebreathing into a paper bag. When frequent auras are troublesome, some experts suggest preventive therapy with aspirin and/or a calcium-entry blocker.

3. Lamictal at low doses (typically <100 mg) may be helpful as preventive for migraine with aura. Therefore, its use can be considered in patients who have exclusively migraine with aura in addition to other more usual classes of preventives

1. Headaches generally respond to simple nonprescription analgesics. Evidence is best for nonsteroidal anti-inflammatory drugs (NSAIDs), but acetaminophen may also be effective. If this treatment is helpful, well tolerated, and infrequent, no additional treatment is needed.

2. In episodic tension-type headache that responds well to simple analgesics, the main role of the doctor is to monitor the frequency of use of abortive medication. As a general rule, this should be limited to no more than 2 to 3 days of use per week to prevent development of medication-overuse headache.

3. Prescription combination analgesic medications such as fixed combination products of butalbital/acetaminophen/caffeine or isometheptene mucate/dichloralphenazone/acetaminophen are generally avoided, and use should be limited to avoid precipitation of medication-overuse headache. Judicious, infrequent use may be appropriate in patients for whom other treatments are contraindicated or ineffective.

4. The use of opioids or sedative medications, although effective for pain relief, is generally discouraged because of concerns about the development of tolerance or addiction.

5. Preventive treatment should be considered if headaches are troublesome or disabling despite optimal abortive therapy, or if headache frequency exceeds twice a week on a regular basis.

6. Effective preventive treatments include the following:

7. Amitriptyline and doxepin are particularly helpful when there is also insomnia because the medications are sedating. Imipramine is less sedating and has fewer anticholinergic side effects, including dry mouth and constipation, but may be less effective.

8. A good starting dose is 10 mg at bedtime, after which the dose is gradually increased as tolerated and as needed. Early evening administration, rather than bedtime dosing, may help reduce morning sedation. The dose of amitriptyline usually required to achieve a beneficial effect in tension headache lies between 10 and 75 mg/d.