Migraine abortives

Marcello Cherchi M.D. Ph.D., Chicago IL and Timothy C. Hain, MD, Chicago IL

Page last modified: July 26, 2020

Migraine abortives are medications taken after a headache starts, in an attempt to prevent it from progressing. They are different from prophylactic drugs (taken daily).

The following incomplete list includes medications, discussed in the medical literature, and each of which has been asked about by patients in our practice in Chicago at some point. The list contains some comments regarding our prescribing practices, but we do not endorse any particular drugs. When applicable, we have added in the recommendations of review articles concerning abortives, such as that by Orr et al (2015), although in many instances these recommendations violate clinical experience and common sense.

This list implies that "migraine" is a monolithic disease where the best treatment can be elucidated by evidence, such as a double-blind placebo controlled trial. Actually, genetic studies suggest that there are many genetic variants associated with the collection of symptoms called "migraine", and a "splitter" could reasonably argue that these are all different diseases. Logically then, medications might work better in genetic subvariants, and the clinical evidence should be looked at as dubious, as it presumes that "migraine" is a disease. In our opinion, clinical experience can help the astute clinician pick medications that are more likely to be effective for variants of "migraine", but often the treatment process involves trial/error.

New drugs:

Not yet FDA approved is Lasmiditan. This is another 5HT drug, working on 5HT1-F. It was developed by Lilly. They filed for FDA approval on Nov 14, 2018. This is likely a "cleaner" Triptan like drug. It will probably work in patients who respond to Triptans, but might have less side effects. Interestingly, dizziness is a very common side effect (16-18%). We would not call this a "break-through" drug, and in fact, since sumatriptan is presently cheap, this will probably have the net effect of increasing the cost of migraine care, as it will replace a cheap drug that works rather well, with an expensive drug that works slightly better. See Kuca et al (2018) for more about efficacy.

Triptans

Triptans are the prototype migraine abortive drug. At this writing, this category includes sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, frovatriptan and eletriptan. These drugs are all group-1 agents. These drugs are 5HT-1B and 1D (serotonin) receptor agonists. Some also affect 5HT-1F. Serotonin does a lot of things in the body and there are many receptors, presently ranging from 5HT1-7. The table below contains an overview of the timing of these drugs. Tmax is the time when the effect peaks. T 1/2 tells you (approximately) how long the effect lasts. As a general rule, it takes 5 half-lives for a drug to be completely eliminated -- thus this varies from about 10 hours to 5 days. The Canadian Headache Society states that they recommend sumatriptan (one of these) based on a "moderate level of evidence" (Orr, 2015). This is reasonable and we think the recommendation applies to almost all triptans. Triptans have good evidence (level A) for effectiveness according to the American Headache Society (Marmura et al, 2015).

Compound Dose Tmax T 1/2 Generic cost/usual rx intending to last 30 days
Rizatriptan (Maxalt) 5-10 1 2-2.5 24.52/18, 25.82/18
Eletriptan (Relpax) 20-40 1-1.25 4-7 86.50/6, 82.53/6
Sumatriptan (Imitrex) 100 2.5 2-2.5 22.09/9
Zolmitriptan (zomig) 2.5 2.5 3 48.06/6
Almotriptan (Axert) 12.5 2.5 3.6 70.96/6
Naratriptan (Amerge) 2.5 2-3 5-6 26.03/9
Frovatriptan (Frova) 2.5 2-4 25 This has gone down !
(modified from Matthew and Loder, 2005) -- Cost data from NMPP (Jan 2018)

Considering cost, the self-pay charge ranges PER PILL from roughly $1.50 (Rizatriptan -- Maxalt), to the nose-bleed price of about $10. These are old medications, many of whom are no longer patent protected. Most of our patients without the best insurance coverage use sumatriptan or rizatriptan.

Cost quoted for brand named versions of these medications is usually astounding -- roughly 10 times the cost of the generic versions. So when your pharmacy says that you saved 1000's of dollars on your triptan, this is how they come up with this figure. One would hope that nobody really pays these gigantic prices and that they are mostly just for show -- sort of like mark downs in department stores. Certain entities (like Medicare) can't negotiate prices of drugs due to the wisdom of our federal government, so they pay the full freight.

Similar medications to the triptans, including ergot drugs, are also priced in nose-bleed territory, some of which are amazingly expensive.

Chemical name: Almotriptan

  • Proprietary names: Axert.
  • Data:Randomized, double-blind, placebo-controlled trials demonstrated the efficacy of this drug (Dahlof et al. 2006; Diener 2005; Dowson et al. 2002; Pascual et al. 2000).
  • Class:Triptan.
  • Mechanism of action: Serotonin receptor agonist with strong affinity for 5-HT1B/1D/1F receptors; weak affinity for 5-HT1A/7 receptors.
  • Pharmacokinetics: Bioavailability 70%; peak concentration at 1-3 hrs.; half-life 3-4 hrs.
  • Metabolism: Monoamine oxidase and CYP-450. Excreted in urine (40%) and feces (13%).
  • Precautions: Contraindicated in patients with cardiovascular disease, uncontrolled hypertension, basilar migraine, hemiplegic migraine.
  • Dosing: 6.25, 12.5 mg
  • Adverse effects: Nausea, somnolence, paresthesias, dry mouth, palpitations.
  • Comments:A medium strength triptan. Little reason to use it over other triptans. We almost never prescribe this short acting drug.

Chemical name: Eletriptan

  • Proprietary names: Relpax.
  • Data:Randomized, double-blind, placebo-controlled trials demonstrated efficacy of this drug (Sandrini et al. 2002; Sheftell et al. 2003; Stark et al. 2002). Several trials demonstrated superiority of eletriptan over sumatriptan (Deleu and Hanssens 2003; Goadsby et al. 2000).
  • Class:Triptan.
  • Mechanism of action: Serotonin receptor agonist with strong affinity for 5-HT1B/1D/1F receptors; weak affinity for 5-HT1A/1E/2B/7 receptors.
  • Pharmacokinetics: Bioavailability 50%; peak concentration achieved at 1.5 hrs, though during an attack can be reached at 2 hrs.; half-life 4 hrs.
  • Metabolism: N‑demethylated by CYP-3A4. Excreted in urine (10%).
  • Precautions: Contraindicated in patients with cerebrovascular, cardiovascular or peripheral vascular disease, uncontrolled hypertension, hemiplegic or basilar migraine, severe hepatic impairment. Avoid within 24 hrs. of using other 5‑HT1 agonists or ergot-type drugs.
  • Dosing: 20 mg, 40 mg.
  • Advantages: Powerful and rapidly acting triptan. It is often available as samples. It is priced roughly at 2X with respect to Rizatriptan (Maxalt), which is almost identical.
  • Adverse effects: Weakness, chest discomfort, dry mouth, paresthesias, fatigue.
  • Comments: We prescribe eletriptan often.

Chemical name: Frovatriptan

  • Proprietary names: Frova. (we advise always getting the generic).
  • Data: A review of randomized trials found this drug to be more efficacious than placebo (Poolsup et al. 2005). Dose-finding studies found 2.5 mg to be the optimal balance between efficacy and tolerability (Goldstein and Keywood 2002; Rapoport et al. 2002). As with other triptans, taking frovatriptan earlier in a migraine attack is more likely to be efficacious (Cady et al. 2004). Several randomized, double-blind, placebo-controlled trials found efficacy of this drug in the unusual use as a prophylactic for menstrual migraine (Adelman and Calhoun 2005; Silberstein et al. 2004).
  • Class: Triptan.
  • Mechanism of action: Serotonin receptor agonist with strong affinity for 5-HT1B/1D receptors
  • Pharmacokinetics: Bioavailability 20% (males), 30% (females); peak concentration achieved at 2-4 hrs.; half-life 26 hrs.
  • Metabolism:Feces (62%), urine (32%).
  • Precautions: Contraindicated in cerebrovascular, cardiovascular and peripheral vascular disease, uncontrolled hypertension, hemiplegic or basilar migraines. Avoid within 24 hrs. of using 5‑HT1 agonists or ergot-type drugs.
  • Dosing: 2.5 mg.
  • Advantages: Long half-life.
  • Adverse effects: Paresthesias, dry mouth, gastric upset, fatigue, flushing.
  • Comments:

    Due to its long half-life, Frova was marketed as effective for menstrual migraines. We find this property to be useful in other migraines as well. Oddly enough, frovatriptan has become far more expensive in recent years (we are writing in 2016), even though generally speaking medications get cheaper as they age. Endo pharmaceuticals, the maker of Frova, has been sued by the FDA for other things (https://www.ftc.gov/news-events/press-releases/2016/03/ftc-sues-endo-pharmaceuticals-inc-others-illegally-blocking-lower). Frovatriptan is now sometimes available at reasonable prices. If not, a reasonable "work around" is to take multiple small doses of sumatriptan, which is priced more reasonably.

Chemical name: Naratriptan

  • Proprietary names: Amerge.
  • Data:

    Randomized, double-blind, placebo-controlled trials (Klassen et al. 1997; Mathew et al. 1997) and dose-ranging trials (Havanka et al. 2000) showed efficacy of naratriptan. A meta-analysis of randomized trials showed that naratriptan is better tolerated than rizatriptan, sumatriptan or zolmitriptan. Its efficacy is poorer than rizatriptan and sumatriptan, but comparable to zolmitriptan. It is also less efficacious than eletriptan (Garcia-Ramos et al. 2003). Several randomized, double-blind, placebo-controlled trials found efficacy of this drug in the unusual use as a prophylactic for menstrual migraine (Mannix et al. 2007b; Newman et al. 2001).

  • Class: Triptan.
  • Mechanism of action: Serotonin receptor agonist, with strong affinity for 5-HT1B/1D receptors.
  • Pharmacokinetics: Bioavailability 70%; peak concentration reached at 2-3 hrs., though during an attack can be reached at 3-4 hrs; elimination half-life 6 hrs.
  • Metabolism: Excreted in urine (50%).
  • Precautions:Contraindicated in patients with uncontrolled hypertension, cerebrovascular, cardiovascular, or peripheral vascular disease, basilar and hemiplegic migraines. Use with caution in renal or hepatic impairment. Avoid within 24 hrs. of using another 5‑HT1 agonist or ergot-type drugs.
  • Dosing: Although a 1 mg dose exists, the 2.5 mg dose is usually used.
  • Advantages:None -- it is not long lasting and not really a good substitute for frovatripan. Small amounts of sumatriptan may be better choice.
  • Adverse effects: Paresthesias, drowsiness, fatigue.
  • Comments:We use this dose for patients who need a weak triptan. Now that frovatriptan has become too expensive for most patients, this is the fallback drug. Unfortunately, it does not last as long as frovatriptan and one would wonder why not just use multiple small doses of sumatriptan instead.

Chemical name: Rizatriptan

  • Proprietary names: Maxalt (tablet), Maxalt-MLT (orally disintegrating wafer)
  • Data: Randomized, double-blind, placebo-controlled studies have shown efficacy of this drug in migrines associated with nausea (Freitag et al. 2008), menstrual migraines (Mannix et al. 2007a), and migraines in adolescents (Winner et al. 2002).
  • Class:Triptan.
  • Mechanism of action: Serotonin receptor agonist with strong affinity for 5-HT1B/1D receptors; weak affinity for 5-HT1A/1E/1F receptors.
  • Pharmacokinetics: Bioavailability 45%; peak concentration 1-1.5 hrs. (tablet) or 1.6-2.5 hrs. (orally disintegrating wafer); half-life 2-3 hrs.
  • Metabolism:Oxidative deamination via monoamine oxidase A. Excreted in urine (82%) and feces (12%).
  • Precautions: Contraindicated in patients with uncontrolled hypertension, cardiovascular disease, hemiplegic or basilar migraines. Avoid within two weeks of using a monoamine oxidase inhibitor or within 24 hrs. of ergot-type drugs or serotonergic drugs.
  • Dosing: 5 mg, 10 mg (tablet or orally disintegrating wafer).
  • Advantages: Has an orally disintegrating wafer formulation. Pricing is more reasonable than other strong triptans (e.g. Relpax).
  • Adverse effects: Paresthesias, dry mouth, nausea, fatigue.
  • Comments:Powerful triptan. Similar to Relpax in strength. High patient acceptance.

Chemical name: Sumatriptan

  • Proprietary names: Imitrex.
  • Data: Randomized, double-blind, placebo-controlled trials have demonstrated the efficacy of oral sumatriptan (Sheftell et al. 2005; Winner et al. 2003), nasal sumatriptan (Winner et al. 2000), and subcutaneous sumatriptan (Russell et al. 1995; Wendt et al. 2006).
  • Class: Triptan.
  • Mechanism of action: Serotonin receptor agonist with strong affinity for 5-HT1D receptors; weak affinity for 5-HT1A/5A/7 receptors.
  • Pharmacokinetics: Oral: bioavailability 15%; peak concentration reached in 2 hrs.; elimination half-life 2.5 hrs. Intranasal: bioavailability 17%; elimination half-life 2 hrs. Subcutaneous: bioavailability 97%; peak concentration reached in 12 min; half-life 115 min. Excreted in urine.
  • Metabolism: Monoamine oxidase.
  • Precautions:Contraindicated in patients with a history of uncontrolled hypertension, cardiovascular, cerebrovascular, or peripheral vascular disease, severe hepatic impairment, hemiplegic or basilar migraines. Avoid within two weeks of using a monoamine oxidase inhibitor or within 24 hrs. of ergotamine-containing agents or other 5‑HT1 drugs.
  • Dosing:50 or 100 mg (oral). 5 or 20 mg (intranasal), 6 mg (subcutaneous).
  • Advantages:Has intranasal and intramuscular formulations.
  • Adverse effects:Palpitations, anxiety, paresthesias, flushing.
  • Comments:

    We prescribe sumatriptan often, more so now that it has achieved generic status.

    Watch out: In 2008 a combination drug of sumatriptan (85 mg) plus naproxen (500 mg) was marketed as a migraine abortive (Treximet). While reasonably effective, one would wonder why one would choose an expensive new brand name product rather than a far cheaper combination of two generic products (i.e. 1.5 sumatriptan 50+naproxen 500). Efficacy was shown in several randomized, double-blind, placebo-controlled trials (Landy et al. 2007). Another such study was funded by the drugs manufacturer, GlaxoSmithKline and Pozen (Brandes et al. 2007).

Chemical name: Zolmitriptan

  • Proprietary names: Zomig (tablet), Zomig-ZMT (orally disintegrating wafer), Zomig intranasal.
  • Data: Randomized, double-blind, placebo-controlled trials demonstrated efficacy similar to sumatriptan (Gruffyd-Jones et al. 2001) and efficacy in menstrual migraine (Loder et al. 2004).
  • Class: Triptan.
  • Mechanism of action: Serotonin receptor agonist with strong affinity for 5-HT1B/1D receptors; weak affinity for 5-HT1A receptors.
  • Pharmacokinetics: Bioavailability 40%; peak concentration reached at 1.5 hr (tablet) or 3 hr (orally disintegrating tablet, nasal). Half-life of the nasal formulation is 3 hrs.
  • Metabolism: Excreted in the urine (65%) and feces (30%).
  • Precautions:Contraindicated in patients with cardiovascular disease, hemiplegic or basilar migraine. Use with caution in patients with hypertension, hepatic or renal impairment.
  • Dosing:2.5 mg, 5 mg (tablet and orally disintegrating wafer), 5 mg (intranasal).
  • Advantages: Has orally disintegrating wafer and intranasal formulations. Practically, almost nobody cares about these. People mainly care about how well things work and what they cost, not whether they taste good.
  • Adverse effects:Parethesias, weakness, dry mouth, nausea. The nasal spray has an unusual taste.
  • Comments:The sublingual form has a pleasant taste (so keep away from small children). We would use this drug in persons in need of a medium strength triptan.

Ergot derivatives

Chemical name: Dihydroergotamine (DHE)

  • Proprietary names: D.H.E. 45
  • Data:

    Parenteral dihydroergotamine has been used in acute treatment of migraines since 1925 (Tfelt-Hansen and Koehler 2008) and has been used quite consistently since then (Becker et al. 1996; Callaham and Raskin 1986; Scott 1992; Winner et al. 1993). One randomized, double-blind study found similar efficacy of subcutaneous dihydroergotamine and subcutaneous sumatriptan found that migraines were less likely to recur in patients treated with dihydroergotamine than with sumatriptan (Winner et al. 1996). Ergot also has a "level A" strength of evidence for efficacy according to the American Headache Society (Marmura et al, 2015).

  • Class: Ergot derivative.
  • Mechanism of action:Vasoconstrictor.
  • Pharmacokinetics: Half-life 9 hrs. Plasma protein binding 93%.
  • Metabolism: Hepatic. Eliminated mostly in feces, only slightly (6-7%) in urine.
  • Precautions Often needs to be administered intravenously in a hospital setting due to adverse effects of nausea and because of the need for cardiac monitoring. Contraindicated in patients with hypertension, cardiovascular or peripheral vascular disease, hemiplegic or basilar migraines, severe renal or hepatic dysfunction. Avoid within 24 hrs. of using 5‑HT1 agonists or other ergot-type medications.
  • Dosing:1 mg intravenous, intramuscular, subcutaneous.
  • Advantages:
  • Adverse effects:Nausea, palpitations, hypertension, anxiety, shortness of breath, flushing, sweating.
  • Comments:We seldom prescribe dihydroergotamine because it requires injection, because of the nausea, and because there are good alternatives. Headache clinics use this drug for intractable migraine.
  •  

    Chemical name: Dihydroergotamine (DHE) nasal

    • Proprietary names: Migranal.
    • Data:

      Several randomized, double-blind, placebo-controlled studies demonstrated the efficacy of dihydroergotamine nasal (Dihydroergotamine Nasal Spray Multicenter Investigators 1995; Ziegler et al. 1994), though one randomized, double-blind, placebo-controlled study found dihydroergotamine nasal to be little better than placebo (Tulunay et al. 1987). A randomized, double-blind, crossover study found dihydroergotamine nasal to be inferior to sumatriptan nasal (Boureau et al. 2000). A crossover study found dihydroergotamine nasal to have slower onset of effect than subcutaneous sumatriptan (Touchon et al. 1996).

    • Class:Ergot derivative.
    • Mechanism of action: Vasoconstrictor.
    • Pharmacokinetics: Bioavailability 32%.
    • Metabolism:Excreted primarily in bile, less (2%) in urine.
    • Precautions:Contraindicated in patients with cardiovascular or peripheral vascular disease, uncontrolled hypertension, hemiplegic or basilar migraine. Avoid within 24 hrs. of using 5‑HT1 agonists or other ergot-type drugs.
    • Children -- according to Valeant, safety in persons under the age of 18 has not been established.
    • Dosing:0.5 mg per spray.
    • Advantages:Nasal formulation.
    • Adverse effects: Rhinitis, altered taste, fatigue.
    • Comments:We occasionally prescribe dihydroergotamine nasal. We see little reason to prescribe it over sumatriptan nasal, as it has more side effects.

    Chemical name: Ergotamine / caffeine

    • Proprietary names: Cafergot.
    • Data: Randomized, double-blind, placebo-controlled and crossover trials found ergotamine + caffeine to be less efficacious than almotriptan (Lainez et al. 2007), eletriptan (Diener et al. 2002), and rizatriptan (Christie et al. 2003). According to the American Headache Society, Ergotamine 1-2 mg + caffeine has only a "level B" evidence for efficacy (Marmura et al, 2015).
    • Class:Ergot derivative and caffeine.
    • Mechanism of action: Ergotamine is an alpha adrenergic blocker that directly stimulates the smooth muscle of cranial blood vessels and produces depression of the central vasomotor center. Caffeine is a cranial vasodilator.
    • Precautions:Contraindicated in patients with hypertension, peripheral vascular disease, hepatic or renal dysfunction.
    • Dosing:1 mg ergotamine, 100 mg caffeine.
    • Advantages:
    • Adverse effects: Chest discomfort, tachycardia or bradycardia, itching, paresthesias, muscle pain, leg weakness. Retroperitoneal and pleuropulmonary fibrosis may result from frequent use.
    • Comments:We rarely prescribe ergotamine for migraine. It is less expensive than triptans.

    Dopamine antagonists

    Chemical name: Chlorpromazine

    • Proprietary names: Thorazine.
    • Data:

      A randomized, double-blind, placebo-controlled trial found some efficacy (McEwen et al. 1987). A randomized, double-blind study with no placebo arm found intravenous chlorpromazine and intravenous metoclopramide to have similar efficacy (Cameron et al. 1995). A randomized, double-blind study with no placebo arm found intravenous chlorpromazine and intravenous ketorolac to have similar efficacy (Shrestha et al. 1996). A randomized, unblinded study with no placebo arm premedicated patients with metoclopramide and then compared intravenous chlorpromazine versus intramuscular sumatriptan, and found similar efficacy (Kelly et al. 1997). The Canadian Headache Society states that they "weakly recommend chlorpromazine based on a moderate level of evidence" (Orr, 2015). This drug is not used commonly in the United States, as there is a general dislike of using powerful antipsychotic drugs to treat benign conditions. According to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015).

    • Class:Phenothiazine (typical antipsychotic).
    • Mechanism of action: Dopamine D2 receptor antagonist. Also has strong anti-adrenergic and weakner peripheral anti-cholinergic activity and ganglionic blocking action (PDR 2009).
    • Pharmacokinetics: Half-life 23-27 hrs.
    • Metabolism:CYP-450. Excreted in urine (37%), bile and feces.
    • Precautions:Caution with respiratory disorders, glaucoma, cardiovascular disease, hepatic or renal impairment.
    • Dosing:12.5 mg IV (Marmura et al, 2015)
    • Advantages:
    • Adverse effects:Tardive dyskinesia, akathesia, neuroleptic malignant syndrome, drowsiness, jaundice, agranulocytosis, hypotension, EKG changes, anticholinergic effects.
    • Comments:We seldom prescribe chlorpromazine for migraine.

    Chemical name: Droperidol

    • Proprietary names: Inapsine.
    • One randomized, double-blind, placebo-controlled, dose-ranging trial found droperidol to be efficacious (Silberstein et al. 2003). A randomized, single-blind study with no placebo arm compared intramuscular droperidol with intramuscular meperidine and found similar efficacy (Richman et al. 2002). According to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015).

    • Class:Butyrophenone (neuroleptic).
    • Mechanism of action: Dopamine D2 receptor antagonist. Also antagonizes alpha-adrenergic receptors.
    • Pharmacokinetics: Half-life 134 min.
    • Metabolism:CYP-450. Excreted in urine (75%), feces (22%).
    • Precautions:Contraindicated in known or suspected QT prolongation. Caution with renal or hepatic impairment, hypertension, pheochromocytoma, electrolyte imbalances, alcohol abuse.
    • Dosing:2.5 mg intramuscular or intravenous. Also 2.75 mg IV (Marmura et al, 2015) It can also be used sublingually.
    • Advantages: Poweful drug for nausea.
    • Adverse effects:Hypotension, tachycardia, dysphoria, drowsiness, restlessness, hyperactivity, anxiety, irregular cardiac rhythm.
    • Comments:We never prescribe droperidol for migraine, primarily due to its risk of cardiac disturbance and the availablity of reasonable alternatives (i.e. haldol).

    Chemical name: Haloperidol

    • Proprietary names:Haldol.
    • Data:A randomized, double-blind, placebo-controlled trial found intravenous haloperidol to be efficacious (Honkaniemi et al. 2006). This drug has not been reviewed by the American Headache Society, but presumably it is similar to Droperidol, as these are closely related.
    • Class:Butyrophenone (neuroleptic).
    • Mechanism of action: Antagonizes dopamine D2 receptors.
    • Pharmacokinetics: Half-life 21-24 hrs.
    • Metabolism: CYP-450. Excreted in urine (40%), feces (15%).
    • Precautions:Contraindicated in Parkinsons disease and depressed states of consciousness. Caution in patients with cardiovascular disease, seizures or EEG abnormalities, QT-prolonging conditions, and in the elderly.
    • Dosing:5 mg oral, often much less will work when used as a sublingual with drops.
    • Advantages:extremely powerful dopamine blocker
    • Adverse effects: Tardive dyskinesia and dystonia, neuroleptic malignant syndrome, hypertension, tachycardia, dry mouth, blurred vision, urinary retention.
    • Comments:We seldom prescribe haloperidol for migraine, primarily due to its adverse effects. It can be very useful however for variants of migraine with powerful nausea, such as basilar artery migraine.

      The Canadian Headache Society states that they "recommend strongly against haloperidol based on a low level of evidence" (Orr, 2015).

    Chemical name: Metoclopramide (+ diphenhydramine)

    • Proprietary names: Reglan (+ Benadryl).
    • Data:

      A meta-analysis of randomized, placebo-controlled trials concluded that metoclopramide is efficacious as a migraine abortive (Colman et al. 2004). An interesting randomized, double-blind trial with no placebo arm compared subcutaneous sumatriptan with repeated doses (up to four) of intravenous metoclopramide (20 mg) in which alternate doses of metoclopramide were given with intravenous diphenhydramine 25 mg (Benadryl). The study found similar efficacy of the two approaches (Friedman et al. 2005). According to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015).

    • Class: Antiemetic.
    • Mechanism of action: Metoclopramide is a dopamine receptor antagonist. Diphenhydramine is a histamine H1 receptor antagonist.
    • Pharmacokinetics: Bioavailability 80%; peak concentration achieved in 1-2 hrs.; plasma protein binding 30%; half-life 5-6 hrs.
    • Metabolism: Excreted in the urine (80%), bile and feces (5%).
    • Precautions: Caution in patients with hypertension, Parkinsons disease or other extrapyramidal disorders.
    • Dosing: 5 mg, 10 mg (oral metoclopramide), 10-20 mg (intravenous metoclopramide).
    • Adverse effects: Tardive dyskinesia, neuroleptic malignant syndrome.
    • Comments: We seldom prescribe metoclopramide alone. We sometimes use the combination of metoclopramide and diphenhydramine in the emergency room setting.

      The Canadian headache society stated that "We strongly recommend the use of .... metoclopramide, based on a moderate level of evidence," (Orr, 2015). This treatment is sometimes used in US emergency departments (i.e. it has stood up to the test of time).

    Chemical name: Prochlorperazine

    • Proprietary names: Compazine.
    • Data:

      A randomized, double-blind, placebo-controlled trial demonstrated the efficacy of intravenous prochlorperazine as a migraine abortive (Coppola et al. 1995). A randomized, double-blind, placebo-controlled trial showed intramuscular prochlorperazine to be more efficacious than intramuscular metoclopramide (Jones et al. 1996). Similarly, another trial in the emergency department reported IV prochlorperazine plus 25 mg of diphenydramine (to prevent dyskinesia) was more effective than 1 mg of hydromorphone (Friedman et al, 2017). . A randomized, double-blind, placebo-controlled trial of rectal prochlorperazine demonstrated efficacy (Jones et al. 1994). According to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015).

      We find these reports amazing and wonder how this could be true, as prochlorperazine does not relieve (for example) pain in other situations. When we suggest that our patients try oral prochloperazine for acute migraine, they almost never report success. We think it is strange that emergency room treatments of migraine are so different than outpatient treatments of acute headache.

    • Class: Antiemetic.
    • Mechanism of action: Dopamine receptor antagonist.
    • Pharmacokinetics: Half-life 3-5 hrs.
    • Metabolism: CYP-450. Excreted in urine, bile and feces.
    • Precautions: Caution in patients with glaucoma, dehydration.
    • Dosing: 5 mg, 10 mg (oral), 25 mg (rectal). Intravenous formulations are also available.
    • Advantages: Has suppository formulation.
    • Adverse effects: Tardive dyskinesia and other extrapyramidal symptoms, neuroleptic malignant syndrome.
    • Comments: We seldom prescribe prochlorperazine for migraine.

    Other Medications for Migraine (non-triptan, non ergot, non anti-emetic)

    butorphanol: This is a rapidly acting opiod. We do not advise using this for migraine due to the high addition risk.

    Acetaminophen/aspirin/caffeine combination: This goes under the general name of "excedrin migraine". This is a mildly effective agent, similar to the combination of a "coke" and aspirin.

    Chemical name: Magnesium sulfate

    • Data:

      A randomized, single-blind, placebo-controlled study found magnesium sulphate 1 g IV over 15 minutes to be efficacious (Demirkaya et al. 2001). A randomized, double-blind, placebo-controlled study found magnesium sulphate to be efficacious for migraine with aura (Bigal et al. 2002). One randomized, double-blind, placebo-controlled trial found intravenous magnesium sulphate to be no more efficacious than placebo as a migraine abortive (Cete et al. 2005). The Canadian Headache Society states that they recommend weakly against the use of magnesium sulfate based on a moderate-quality evidence (Orr, 2015). According to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015). We ourselves think that Magnesium supplements are often helpful for migraine, in a dose of 500 mg orally/day.

    • Class: Mineral.
    • Precautions: Intravenous magnesium should be administered in a monitored setting due to the risk of cardiac arrhythmias and respiratory depression.
    • Dosing:1 g intravenous over 15 minutes.Or 1-2 g, according to Marmura et al (2015). The oral dose is about 400-800/day.
    • Advantages: Can be used in pregnancy.
    • Adverse effects: Cardiac arrhythmias, depression of muscle reflexes, hypocalcemia.

    Chemical name: Meperidine + promethazine

    • Proprietary names: Demerol + Phenergan
    • Data: One randomized, double-blind study with no placebo arm compared meperidine + promethazine versus dihydroergotamine + metoclopramide and found both similarly efficacious, but the meperidine + promethazine arm was better tolerated (Scherl and Wilson 1995). One randomized, double-blind study with no placebo arm compared ketorolac to meperidine + promethazine and found no statistically significant difference (Davis et al. 1995). See more notes below concerning opiates.
    • Class: Meperidine is an opioid analgesic. Promethazine is a phenothiazine derivative with antiemetic and sedative properties.
    • Mechanism of action: Meperidine is an opinoid receptor agonist. Promethazine antagonizes histamine H1 receptors.
    • Pharmacokinetics:
    • Metabolism:
    • Precautions: Contraindicated in patients with head injury, increased intracranial pressure, intracranial lesions, asthma or other respiratory impairment, hypotension, cardiac arrhythmias. Avoid within 14 days of using monoamine oxidase inhibitors.
    • Dosing: One tablet contains meperidine 50 mg + promethazine 25 mg.
    • Advantages:
    • Adverse effects: Lightheadedness, sedation, sweating. Meperidine is potentially addictive.
    • Comments:We almost never prescribe this combination.

    Chemical name: Methylprednisolone

    • Proprietary names: Medrol Dose Pack
    • Data:There are no convincing data from randomized, double-blind, placebo-controlled trials showing any corticosteroid is an effective migraine abortive. Nevertheless, it continues to be used, largely based on anecdotal experience. A randomized, double-blind, placebo-controlled trial of dexamethasone (a different steroid) showed no efficacy (Rowe et al. 2008). According to the American Headache society, the evidence for efficacy for steroids including hydrocortisone IV is level U (Marmura et al, 2015).
    • Class: Glucocorticoid (similar to cortisone)
    • Mechanism of action: Anti-inflammatory effects.
    • Pharmacokinetics:
    • Metabolism:
    • Precautions:Avoid in patients with active systemic fungal infections.
    • Dosing: Down-tapering dose from 32 mg to 4 mg.
    • Advantages:
    • Adverse effects:Agitation, insomnia, hypertension, hyperglycemia.
    • Comments:This drug is reasonable to try in pregnancy when other medications cannot be used.

      The Canadian Headache Society states that they "strongly recommend against the use of dexamethasone based on a moderate level of evidence" (Orr, 2015). Dexamethasone and methylprednisoline are both steriods and are closely related. That being said, as of 2016, medrol dose packs are commonly used to treat migraine flare ups.

    Chemical name:                 IV valproate

    • Data:                               Friedman et al (2014) reported that IV valproate was less effective than either metoclopramide or ketorolac for acute migraine.

      The Canadian Headache Society states that they "recommend weakly against sodium valproate based on a low level of evidence" (Orr, 2015).

    Caffeine, aspirin, acetaminophen. Efficacy of each drug individually was shown in randomized, double-blind, placebo-controlled trials (Smith 1998).

    Nonsteroidals

    Nonsteroidal antiinflammatory agents include aspirin, naproxen, ibuprofen, and an immense number of other pain relievers. They share several features -- they are generally not addictive, they generally irritate the stomach, and they occasionally are associated with increased blood pressure and worsening of kidney function. Many of these are "OTC" or over the counter agents. Recently there have been a few that seem particularly suitable for migraine treatment.

    We generally first suggest patients try the simple OTC NSAID's such as aspirin (500 mg). This includes some combination products such as "Excedrin migraine". If this is not enough, then we often suggest indomethacin (indocin), with care not to take it very often because of stomach irritation.

    Cambia (diclofenac 50mg) -- a powder that is dissolved in your liquid of choice. Again, very powerful. The Candian headache society disagrees saying that "based on low-quality evidence, we recommend weakly against the use of diclofenac" (Orr, 2015). This adverse recommendation is routinely contradicted by our patients who say that Cambia works very well. We think it is especially helpful in hemiplegic migraine. According to the American Headache society, the evidence for efficacy is level A (Marmura et al, 2015). Cambia is a very expensive ground-up version of an old cheap drug, with the brand name of Volteran, which comes in 25 mg tablets. Some patients just use the generic diclofenac. Of course, it doesn't come in a powder this way. One would wonder why diclofenac works so well when other NSAID's don't seem to work as well. Presumably they all do the same thing.

    Naproxen was studied in randomized, double-blind, placebo-controlled trials (Andersson et al. 1989). The trial showed that naproxen diminished headache severity at 2 hrs., though it did not improve the attack overall. A double-blind, parallel group study found naproxen and ergotamine to have similar efficacy (Treves et al. 1992). The typical dose is 500 or 550. According to the American Headache society, the evidence for efficacy is level A (Marmura et al, 2015).

    Ketoprofen (Orudis) 100 mg has, according to the American Headache society, evidence for efficacy at level B (Marmura et al, 2015).

    Ketorolac (Toradol). The Canadian headache society stated that " We strongly recommend the use of ... ketorolac, based on a low level of evidence". (Orr, 2015) Our take on this is that all of the nonsteroidals do the same thing, and they should all work.

    The American Headache Society had no comments about the Cox-2 NSAID's (such as Celebrex) for migraine (Marmura, 2015). We have not encountered their use at all in our patients in Chicago. One would think that they would work too, perhaps with less stomach upset, but perhaps with more cardiovasacular risk than the non-selective NSAIDs.

    Newer nonsteroidal agents that can be used as abortives in migraine include

    SPRIX (nasal spray form of ketorolac, https://www.sprix.com/Home.aspx) -- is a very powerful drug. According to the American Headache society, the evidence for efficacy is level C negative (Marmura et al, 2015). This would suggest that it is not effective. On the other hand, ketorolac IV or IM (30-60 mg) is, according to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015). So as of 2015, it would seem that Sprix is not effective, but IV or IM ketorolac is effective. This is hard to follow.

    The combination of indomethacin, prochlorperazine and caffeine suppositories was shown to be comparable to sumatriptan in a randomized, double-blind, parallel group trial (Sandrini et al. 2007), and was shown to be more efficacious than sumatriptan in a randomized, double-blind, crossover trial (Di Monda et al. 2003). This formulation is not generally available.

    Opiates (i.e. codeine, oxycodone, etc).

    Most neurologists are very reluctant to prescribe opiates for Migraine because there is a strong tendency to develop addiction. These include butorphanol IM, Codeine 30, Meperidine (demerol) IM 75, Methadone IM 10, Tramadol IV 100. According to the American Headache society, the evidence for efficacy is level C (Marmura et al, 2015). Strangely, missing from this list provided by the American Headache Society, is oxocodone, which we feel is used very commonly. It is certainly addictive as well. There are many other opiates -- addiction is the problem common to all of them. We think in most situations, it is best to avoid them.

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